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wiki20220301en020_104627	Jamie-Lynn Sigler	Filmography Film Television Music videos Discography 2001: Here to Heaven References External links 1981 births Living people 20th-century American actresses 20th-century Sephardi Jews Actresses from New York (state) American child actresses American film actresses American people of Cuban descent American people of Greek-Jewish descent American people of Romanian-Jewish descent American Ashkenazi Jews American Sephardic Jews American television actresses Hispanic and Latino American actresses Jewish American actresses Jewish American musicians People from Jericho, New York People from Queens, New York Singers from New York (state) People with multiple sclerosis 21st-century American singers 21st-century American women singers 21st-century Sephardi Jews 21st-century American actresses 21st-century American Jews	Jamie-Lynn Sigler. Filmography Film Television Music videos Discography 2001: Here to Heaven References External links 1981 births Living people 20th-century American actresses 20th-century Sephardi Jews Actresses from New York (state) American child actresses American film actresses American people of Cuban descent American people of Greek-Jewish descent American people of Romanian-Jewish descent American Ashkenazi Jews American Sephardic Jews American television actresses Hispanic and Latino American actresses Jewish American actresses Jewish American musicians People from Jericho, New York People from Queens, New York Singers from New York (state) People with multiple sclerosis 21st-century American singers 21st-century American women singers 21st-century Sephardi Jews 21st-century American actresses 21st-century American Jews	524375
wiki20220301en020_104628	University Radio Nottingham	University Radio Nottingham is the university radio station of the University of Nottingham, England, where it is part of the Students' Union. During term-time it broadcasts locally on University Park Campus on 1350 AM and worldwide via its website. History URN was established from the University's Radio Broadcasting Club, who, in the late 1970s had an hour's slot on BBC Radio Nottingham. The station set up its first studio in the Cherry Tree buildings in 1978 and "University Radio Nottingham" started broadcasting to Hugh Stewart Hall and Cripps Hall of residence on 963 kHz (312m) in November 1979. Additional induction loops were set up over the next few years in other halls on campus. A fifth induction loop was installed on Sutton Bonington Campus in 1990, financed by their Guild. In 1997, URN became one of the first radio stations to broadcast on the internet using the MP3 format. The station started broadcasting in the Ogg Vorbis format in 2002.	University Radio Nottingham. University Radio Nottingham is the university radio station of the University of Nottingham, England, where it is part of the Students' Union. During term-time it broadcasts locally on University Park Campus on 1350 AM and worldwide via its website. History URN was established from the University's Radio Broadcasting Club, who, in the late 1970s had an hour's slot on BBC Radio Nottingham. The station set up its first studio in the Cherry Tree buildings in 1978 and "University Radio Nottingham" started broadcasting to Hugh Stewart Hall and Cripps Hall of residence on 963 kHz (312m) in November 1979. Additional induction loops were set up over the next few years in other halls on campus. A fifth induction loop was installed on Sutton Bonington Campus in 1990, financed by their Guild. In 1997, URN became one of the first radio stations to broadcast on the internet using the MP3 format. The station started broadcasting in the Ogg Vorbis format in 2002.	524377
wiki20220301en020_104629	University Radio Nottingham	In 1997, URN became one of the first radio stations to broadcast on the internet using the MP3 format. The station started broadcasting in the Ogg Vorbis format in 2002. The station was one of the first to broadcast using an LPAM long-term restricted service licence to the whole of University Park on 1350AM in 2001. In 2004, URN moved into new purpose build studios located in the University's Portland Building. This was due to the demolition of the Cherry Tree buildings in 2003. During the summer of 2012 the whole station was refitted to use a Studer digital system for audio routing and mixing. In the Summer of 2018 the station was relocated in the Students' Union Building to the new MediaZone. A brand new AoIP Studio was installed in Spring 2020.	University Radio Nottingham. In 1997, URN became one of the first radio stations to broadcast on the internet using the MP3 format. The station started broadcasting in the Ogg Vorbis format in 2002. The station was one of the first to broadcast using an LPAM long-term restricted service licence to the whole of University Park on 1350AM in 2001. In 2004, URN moved into new purpose build studios located in the University's Portland Building. This was due to the demolition of the Cherry Tree buildings in 2003. During the summer of 2012 the whole station was refitted to use a Studer digital system for audio routing and mixing. In the Summer of 2018 the station was relocated in the Students' Union Building to the new MediaZone. A brand new AoIP Studio was installed in Spring 2020.	524377
wiki20220301en020_104630	University Radio Nottingham	In the Summer of 2018 the station was relocated in the Students' Union Building to the new MediaZone. A brand new AoIP Studio was installed in Spring 2020. Programming URN broadcasts twenty-four hours a day during Nottingham term time, with shows from 09:00 a.m to 3:00 a.m. The station is split into three sections: Daytime, After Dark, and Speech shows. URN's programming includes news-show The Pulse, feature-based speech programming, including sport and a large variety of other topics, daytime personality-based programming and evening specialist music shows. URN has a strong focus on Nottingham University students in all areas of its programming. Stunts URN once held the world record for the longest continuous broadcast by a single presenter at 42 hours. More recently, Steve Doran accomplished a 40-hour continuous broadcast in November 2005 for Children in Need. In 2016, four teams walked 50 miles in under 24 hours in aid of Sport Relief.	University Radio Nottingham. In the Summer of 2018 the station was relocated in the Students' Union Building to the new MediaZone. A brand new AoIP Studio was installed in Spring 2020. Programming URN broadcasts twenty-four hours a day during Nottingham term time, with shows from 09:00 a.m to 3:00 a.m. The station is split into three sections: Daytime, After Dark, and Speech shows. URN's programming includes news-show The Pulse, feature-based speech programming, including sport and a large variety of other topics, daytime personality-based programming and evening specialist music shows. URN has a strong focus on Nottingham University students in all areas of its programming. Stunts URN once held the world record for the longest continuous broadcast by a single presenter at 42 hours. More recently, Steve Doran accomplished a 40-hour continuous broadcast in November 2005 for Children in Need. In 2016, four teams walked 50 miles in under 24 hours in aid of Sport Relief.	524377
wiki20220301en020_104631	University Radio Nottingham	Regan Gishen (Modulo) once did a 24 broadcast on URN. During which he broke his leg, but continued to broadcast his show in agony. He is quoted as saying "I am a man who delivers music to his people." Famous alumni The former head of music for URN presented BBC 6 Music's weekly chart show. Philippa Treverton-Jones graduated in 2007. Another former presenter on the station; Ian Chaloner is the current producer of the Greg James Show on BBC Radio 1. References External links Introduction to URN URN History Project Farm Student radio in the United Kingdom Music in Nottinghamshire Radio stations established in 1979 Mass media in Nottingham Radio stations in Nottinghamshire	University Radio Nottingham. Regan Gishen (Modulo) once did a 24 broadcast on URN. During which he broke his leg, but continued to broadcast his show in agony. He is quoted as saying "I am a man who delivers music to his people." Famous alumni The former head of music for URN presented BBC 6 Music's weekly chart show. Philippa Treverton-Jones graduated in 2007. Another former presenter on the station; Ian Chaloner is the current producer of the Greg James Show on BBC Radio 1. References External links Introduction to URN URN History Project Farm Student radio in the United Kingdom Music in Nottinghamshire Radio stations established in 1979 Mass media in Nottingham Radio stations in Nottinghamshire	524377
wiki20220301en020_104632	Rantoul	Rantoul may refer to: Places In the United States: Rantoul, Illinois Rantoul (Amtrak station), a train station in Rantoul, Illinois Rantoul, Kansas Rantoul, Wisconsin People Robert Rantoul, Jr., US Senator and US Representative from Massachusetts Robert S. Rantoul, mayor of Salem, Massachusetts	Rantoul. Rantoul may refer to: Places In the United States: Rantoul, Illinois Rantoul (Amtrak station), a train station in Rantoul, Illinois Rantoul, Kansas Rantoul, Wisconsin People Robert Rantoul, Jr., US Senator and US Representative from Massachusetts Robert S. Rantoul, mayor of Salem, Massachusetts	524379
wiki20220301en020_104633	Metacity	Metacity was the default window manager used by the GNOME 2 desktop environment until it was replaced by Mutter in GNOME 3. It is still used by GNOME Flashback, a session for GNOME 3 that provides a similar user experience to the Gnome 2.x series sessions. The development of Metacity was started by Havoc Pennington and it was released under the GNU General Public License. Before the introduction of Metacity in GNOME 2.2, GNOME used Enlightenment and then Sawfish as its window manager. Although Metacity was designed to integrate into the GNOME desktop, it does not require it to run, while GNOME can be used with different window managers provided that they support the part of the ICCCM specification that GNOME requires. Metacity uses the GTK graphical widget toolkit to create its user interface components, which makes it themeable and makes it blend in with other GTK applications. Originally, Metacity used GTK 2 however as of version 3.12.0 it has been ported to GTK 3.	Metacity. Metacity was the default window manager used by the GNOME 2 desktop environment until it was replaced by Mutter in GNOME 3. It is still used by GNOME Flashback, a session for GNOME 3 that provides a similar user experience to the Gnome 2.x series sessions. The development of Metacity was started by Havoc Pennington and it was released under the GNU General Public License. Before the introduction of Metacity in GNOME 2.2, GNOME used Enlightenment and then Sawfish as its window manager. Although Metacity was designed to integrate into the GNOME desktop, it does not require it to run, while GNOME can be used with different window managers provided that they support the part of the ICCCM specification that GNOME requires. Metacity uses the GTK graphical widget toolkit to create its user interface components, which makes it themeable and makes it blend in with other GTK applications. Originally, Metacity used GTK 2 however as of version 3.12.0 it has been ported to GTK 3.	524380
wiki20220301en020_104634	Metacity	Aim Metacity's focus is on simplicity and usability rather than novelties. Its author has characterized it as a "Boring window manager for the adult in you. Many window managers are like Marshmallow Froot Loops; Metacity is like Cheerios." People in favour of Metacity say that it is aimed at new computer users who do not need the abundant options and functionality of Sawfish or Enlightenment. Havoc Pennington wrote an essay explaining why he wrote Metacity and simplified the GNOME desktop. Themes Despite the incomplete state of Metacity theme development documentation, many themes have been written for Metacity. A popular theme engine is Clearlooks, which was the default in GNOME from version 2.12 until the release of GNOME 3 and GNOME Shell. See also Comparison of X window managers References External links Metacity blog Metacity Download Site Metacity Themes Understanding Metacity Themes, Thomas Thurman	Metacity. Aim Metacity's focus is on simplicity and usability rather than novelties. Its author has characterized it as a "Boring window manager for the adult in you. Many window managers are like Marshmallow Froot Loops; Metacity is like Cheerios." People in favour of Metacity say that it is aimed at new computer users who do not need the abundant options and functionality of Sawfish or Enlightenment. Havoc Pennington wrote an essay explaining why he wrote Metacity and simplified the GNOME desktop. Themes Despite the incomplete state of Metacity theme development documentation, many themes have been written for Metacity. A popular theme engine is Clearlooks, which was the default in GNOME from version 2.12 until the release of GNOME 3 and GNOME Shell. See also Comparison of X window managers References External links Metacity blog Metacity Download Site Metacity Themes Understanding Metacity Themes, Thomas Thurman	524380
wiki20220301en020_104635	Metacity	See also Comparison of X window managers References External links Metacity blog Metacity Download Site Metacity Themes Understanding Metacity Themes, Thomas Thurman Free software programmed in C Free X window managers GNOME Window managers that use GTK	Metacity. See also Comparison of X window managers References External links Metacity blog Metacity Download Site Metacity Themes Understanding Metacity Themes, Thomas Thurman Free software programmed in C Free X window managers GNOME Window managers that use GTK	524380
wiki20220301en020_104636	Ranunculus	Ranunculus is a large genus of about 600 species of flowering plants in the family Ranunculaceae. Members of the genus are known as buttercups, spearworts and water crowfoots. The familiar and widespread buttercup of gardens throughout Northern Europe (and introduced elsewhere) is the creeping buttercup Ranunculus repens, which has extremely tough and tenacious roots. Two other species are also widespread, the bulbous buttercup Ranunculus bulbosus and the much taller meadow buttercup Ranunculus acris. In ornamental gardens, all three are often regarded as weeds. Buttercups usually flower in the spring, but flowers may be found throughout the summer, especially where the plants are growing as opportunistic colonizers, as in the case of garden weeds.	Ranunculus. Ranunculus is a large genus of about 600 species of flowering plants in the family Ranunculaceae. Members of the genus are known as buttercups, spearworts and water crowfoots. The familiar and widespread buttercup of gardens throughout Northern Europe (and introduced elsewhere) is the creeping buttercup Ranunculus repens, which has extremely tough and tenacious roots. Two other species are also widespread, the bulbous buttercup Ranunculus bulbosus and the much taller meadow buttercup Ranunculus acris. In ornamental gardens, all three are often regarded as weeds. Buttercups usually flower in the spring, but flowers may be found throughout the summer, especially where the plants are growing as opportunistic colonizers, as in the case of garden weeds.	524383
wiki20220301en020_104637	Ranunculus	Buttercups usually flower in the spring, but flowers may be found throughout the summer, especially where the plants are growing as opportunistic colonizers, as in the case of garden weeds. The water crowfoots (Ranunculus subgenus Batrachium), which grow in still or running water, are sometimes treated in a separate genus Batrachium (from Greek , "frog"). They have two different leaf types, thread-like leaves underwater and broader floating leaves. In some species, such as R. aquatilis, a third, intermediate leaf type occurs. Ranunculus species are used as food by the larvae of some Lepidoptera species including the Hebrew character and small angle shades. Some species are popular ornamental flowers in horticulture, with many cultivars selected for large and brightly coloured flowers. Description	Ranunculus. Buttercups usually flower in the spring, but flowers may be found throughout the summer, especially where the plants are growing as opportunistic colonizers, as in the case of garden weeds. The water crowfoots (Ranunculus subgenus Batrachium), which grow in still or running water, are sometimes treated in a separate genus Batrachium (from Greek , "frog"). They have two different leaf types, thread-like leaves underwater and broader floating leaves. In some species, such as R. aquatilis, a third, intermediate leaf type occurs. Ranunculus species are used as food by the larvae of some Lepidoptera species including the Hebrew character and small angle shades. Some species are popular ornamental flowers in horticulture, with many cultivars selected for large and brightly coloured flowers. Description	524383
wiki20220301en020_104638	Ranunculus	Buttercups are mostly perennial, but occasionally annual or biennial, herbaceous, aquatic or terrestrial plants, often with leaves in a rosette at the base of the stem. In many perennial species runners are sent out that will develop new plants with roots and rosettes at the distanced nodes. The leaves lack stipules, have petioles, are palmately veined, entire, more or less deeply incised, or compound, and leaflets or leaf segments may be very fine and linear in aquatic species. The hermaphrodite flowers are single or in a cyme, have usually five (but occasionally as few as three or as many as seven) mostly green sepals and usually, five yellow, greenish or white petals that are sometimes flushed with red, purple or pink (but the petals may be absent or have a different, sometimes much higher number). At the base of each petal is usually one nectary gland that is naked or may be covered by a scale. Anthers may be few, but often many are arranged in a spiral, are yellow or sometimes	Ranunculus. Buttercups are mostly perennial, but occasionally annual or biennial, herbaceous, aquatic or terrestrial plants, often with leaves in a rosette at the base of the stem. In many perennial species runners are sent out that will develop new plants with roots and rosettes at the distanced nodes. The leaves lack stipules, have petioles, are palmately veined, entire, more or less deeply incised, or compound, and leaflets or leaf segments may be very fine and linear in aquatic species. The hermaphrodite flowers are single or in a cyme, have usually five (but occasionally as few as three or as many as seven) mostly green sepals and usually, five yellow, greenish or white petals that are sometimes flushed with red, purple or pink (but the petals may be absent or have a different, sometimes much higher number). At the base of each petal is usually one nectary gland that is naked or may be covered by a scale. Anthers may be few, but often many are arranged in a spiral, are yellow or sometimes	524383
wiki20220301en020_104639	Ranunculus	higher number). At the base of each petal is usually one nectary gland that is naked or may be covered by a scale. Anthers may be few, but often many are arranged in a spiral, are yellow or sometimes white, and with yellow pollen. The sometimes few but mostly many green or yellow carpels are not fused and are also arranged in a spiral, mostly on a globe or dome-shaped receptacle. The fruits (in this case called achenes) may be smooth or hairy, winged, nobby or have hooked spines.	Ranunculus. higher number). At the base of each petal is usually one nectary gland that is naked or may be covered by a scale. Anthers may be few, but often many are arranged in a spiral, are yellow or sometimes white, and with yellow pollen. The sometimes few but mostly many green or yellow carpels are not fused and are also arranged in a spiral, mostly on a globe or dome-shaped receptacle. The fruits (in this case called achenes) may be smooth or hairy, winged, nobby or have hooked spines.	524383
wiki20220301en020_104640	Ranunculus	Reflective petals The petals of buttercups are often highly lustrous, especially in yellow species, owing to a special coloration mechanism: the petal's upper surface is very smooth causing a mirror-like reflection. The flash aids in attracting pollinating insects and temperature regulation of the flower's reproductive organs. Naming The name Ranunculus is Late Latin for "little frog", the diminutive of rana. This probably refers to many species being found near water, like frogs. The name buttercup may derive from a false belief that the plants give butter its characteristic yellow hue (in fact it is poisonous to cows and other livestock). A popular children's game involves holding a buttercup up to the chin; a yellow reflection is supposed to indicate a fondness for butter. In ancient Rome, a species of buttercup was held to the skin by slaves attempting to remove forehead tattoos made by their owners.	Ranunculus. Reflective petals The petals of buttercups are often highly lustrous, especially in yellow species, owing to a special coloration mechanism: the petal's upper surface is very smooth causing a mirror-like reflection. The flash aids in attracting pollinating insects and temperature regulation of the flower's reproductive organs. Naming The name Ranunculus is Late Latin for "little frog", the diminutive of rana. This probably refers to many species being found near water, like frogs. The name buttercup may derive from a false belief that the plants give butter its characteristic yellow hue (in fact it is poisonous to cows and other livestock). A popular children's game involves holding a buttercup up to the chin; a yellow reflection is supposed to indicate a fondness for butter. In ancient Rome, a species of buttercup was held to the skin by slaves attempting to remove forehead tattoos made by their owners.	524383
wiki20220301en020_104641	Ranunculus	In the interior of the Pacific Northwest of the United States, the buttercup is called "Coyote's eyes"— in Nez Perce and in Sahaptin. In the legend, Coyote was tossing his eyes up in the air and catching them again when Eagle snatched them. Unable to see, Coyote made eyes from the buttercup.	Ranunculus. In the interior of the Pacific Northwest of the United States, the buttercup is called "Coyote's eyes"— in Nez Perce and in Sahaptin. In the legend, Coyote was tossing his eyes up in the air and catching them again when Eagle snatched them. Unable to see, Coyote made eyes from the buttercup.	524383
wiki20220301en020_104642	Ranunculus	Splitting of the genus Molecular investigation of the genus has revealed that Ranunculus is not monophyletic with respect to a number of other recognized genera in the family—e.g. Ceratocephala, Halerpestes, Hamadryas, Laccopetalum, Myosurus, Oxygraphis, Paroxygraphis and Trautvetteria. A proposal to split Ranunculus into several genera has thus been published in a new classification for the tribe Ranunculeae. The split (and often re-recognized) genera include Arcteranthis Greene, Beckwithia Jeps., Callianthemoides Tamura, Coptidium (Prantl) Beurl. ex Rydb., Cyrtorhyncha Nutt. ex Torr. & A.Gray, Ficaria Guett., Krapfia DC., Kumlienia E. Greene and Peltocalathos Tamura. Not all taxonomists and users accept this splitting of the genus, and it can alternatively be treated in the broad sense.	Ranunculus. Splitting of the genus Molecular investigation of the genus has revealed that Ranunculus is not monophyletic with respect to a number of other recognized genera in the family—e.g. Ceratocephala, Halerpestes, Hamadryas, Laccopetalum, Myosurus, Oxygraphis, Paroxygraphis and Trautvetteria. A proposal to split Ranunculus into several genera has thus been published in a new classification for the tribe Ranunculeae. The split (and often re-recognized) genera include Arcteranthis Greene, Beckwithia Jeps., Callianthemoides Tamura, Coptidium (Prantl) Beurl. ex Rydb., Cyrtorhyncha Nutt. ex Torr. & A.Gray, Ficaria Guett., Krapfia DC., Kumlienia E. Greene and Peltocalathos Tamura. Not all taxonomists and users accept this splitting of the genus, and it can alternatively be treated in the broad sense.	524383
wiki20220301en020_104643	Ranunculus	Pharmacological activity The most common uses of Ranunculus species in traditional medicines are as a antirheumatic, as a rubefacient, and to treat intermittent fever. The findings in some Ranunculus species of, for example, protoanemonin, anemonin, may justify the uses of these species against fever, rheumatism and rubefacient in Asian traditional medicines.	Ranunculus. Pharmacological activity The most common uses of Ranunculus species in traditional medicines are as a antirheumatic, as a rubefacient, and to treat intermittent fever. The findings in some Ranunculus species of, for example, protoanemonin, anemonin, may justify the uses of these species against fever, rheumatism and rubefacient in Asian traditional medicines.	524383
wiki20220301en020_104644	Ranunculus	Toxicity All Ranunculus (buttercup) species are poisonous when eaten fresh, but their acrid taste and the blistering of the mouth caused by their poison means they are usually left uneaten. Poisoning in livestock can occur where buttercups are abundant in overgrazed fields where little other edible plant growth is left, and the animals eat them out of desperation. Symptoms of poisoning include bloody diarrhea, excessive salivation, colic, and severe blistering of the mouth, mucous membranes and gastrointestinal tract. When Ranunculus plants are handled, naturally occurring ranunculin is broken down to form protoanemonin, which is known to cause contact dermatitis in humans and care should therefore be exercised in extensive handling of the plants. The toxins are degraded by drying, so hay containing dried buttercups is safe.	Ranunculus. Toxicity All Ranunculus (buttercup) species are poisonous when eaten fresh, but their acrid taste and the blistering of the mouth caused by their poison means they are usually left uneaten. Poisoning in livestock can occur where buttercups are abundant in overgrazed fields where little other edible plant growth is left, and the animals eat them out of desperation. Symptoms of poisoning include bloody diarrhea, excessive salivation, colic, and severe blistering of the mouth, mucous membranes and gastrointestinal tract. When Ranunculus plants are handled, naturally occurring ranunculin is broken down to form protoanemonin, which is known to cause contact dermatitis in humans and care should therefore be exercised in extensive handling of the plants. The toxins are degraded by drying, so hay containing dried buttercups is safe.	524383
wiki20220301en020_104645	Ranunculus	Fossil record †Ranunculus gailensis and †Ranunculus tanaiticus seed fossils have been described from the Pliocene Borsoni Formation in the Rhön Mountains, central Germany. Species See also List of plants poisonous to equines References Notes General sources External links All about the Ranunculus The Ranunculus home page The Flower (Ranunculus) Fields of Carlsbad, CA Ranunculaceae genera Taxa named by Carl Linnaeus	Ranunculus. Fossil record †Ranunculus gailensis and †Ranunculus tanaiticus seed fossils have been described from the Pliocene Borsoni Formation in the Rhön Mountains, central Germany. Species See also List of plants poisonous to equines References Notes General sources External links All about the Ranunculus The Ranunculus home page The Flower (Ranunculus) Fields of Carlsbad, CA Ranunculaceae genera Taxa named by Carl Linnaeus	524383
wiki20220301en020_104646	Lorraine Bracco	Lorraine Bracco (born October 2, 1954) is an American film and television actress. Known for her distinct husky voice and Brooklyn accent, she has been nominated for an Academy Award, four Emmy Awards, four Golden Globe Awards, and three Screen Actors Guild Awards. Born in New York City, she began her career modeling in France and began appearing in Italian-language films in the 1980s, including Lina Wertmüller's Camorra (1986), which featured Bracco's then-partner Harvey Keitel. Bracco's English-language debut came in The Pick-Up Artist (1987), which was followed by roles in Someone to Watch Over Me (1987), Sing (1989), and The Dream Team (1989). Her breakthrough role was that of Karen Hill, wife of mob associate Henry Hill, in Martin Scorsese's Goodfellas (1990), for which she was nominated for the Academy Award for Best Supporting Actress and the Golden Globe Award for Best Supporting Actress – Motion Picture.	Lorraine Bracco. Lorraine Bracco (born October 2, 1954) is an American film and television actress. Known for her distinct husky voice and Brooklyn accent, she has been nominated for an Academy Award, four Emmy Awards, four Golden Globe Awards, and three Screen Actors Guild Awards. Born in New York City, she began her career modeling in France and began appearing in Italian-language films in the 1980s, including Lina Wertmüller's Camorra (1986), which featured Bracco's then-partner Harvey Keitel. Bracco's English-language debut came in The Pick-Up Artist (1987), which was followed by roles in Someone to Watch Over Me (1987), Sing (1989), and The Dream Team (1989). Her breakthrough role was that of Karen Hill, wife of mob associate Henry Hill, in Martin Scorsese's Goodfellas (1990), for which she was nominated for the Academy Award for Best Supporting Actress and the Golden Globe Award for Best Supporting Actress – Motion Picture.	524384
wiki20220301en020_104647	Lorraine Bracco	On television, Bracco is best known for portraying Jennifer Melfi, the psychiatrist of Tony Soprano, in the HBO series The Sopranos (1999-2007). She was nominated for the Primetime Emmy Award for Outstanding Lead Actress in a Drama Series and the Golden Globe Award for Best Actress – Television Series Drama for her performance across the show's first three seasons. Beginning with the fourth season her role began to decline slightly, though by the end of the series, at the 59th Primetime Emmy Awards, she was nominated for the Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series. Early life	Lorraine Bracco. On television, Bracco is best known for portraying Jennifer Melfi, the psychiatrist of Tony Soprano, in the HBO series The Sopranos (1999-2007). She was nominated for the Primetime Emmy Award for Outstanding Lead Actress in a Drama Series and the Golden Globe Award for Best Actress – Television Series Drama for her performance across the show's first three seasons. Beginning with the fourth season her role began to decline slightly, though by the end of the series, at the 59th Primetime Emmy Awards, she was nominated for the Primetime Emmy Award for Outstanding Supporting Actress in a Drama Series. Early life	524384
wiki20220301en020_104648	Lorraine Bracco	Early life Bracco was born on October 2, 1954, in the Bay Ridge neighborhood of Brooklyn, New York City. She is the daughter of Eileen (née Molyneux) and Salvatore Bracco, Sr. She has a sister, actress Elizabeth Bracco, and a brother, Salvatore, Jr. Her father was of Italian descent, while her mother was born in England, and had some French ancestry. Her parents met during World War II; Eileen came with Salvatore to the United States as a war bride. Bracco grew up in Hicksville, New York, on Long Island, from fourth grade. Bracco graduated from Hicksville High School in 1972. Career Bracco moved to France in 1974, where she became a fashion model for Jean-Paul Gaultier. She lived there for about a decade.	Lorraine Bracco. Early life Bracco was born on October 2, 1954, in the Bay Ridge neighborhood of Brooklyn, New York City. She is the daughter of Eileen (née Molyneux) and Salvatore Bracco, Sr. She has a sister, actress Elizabeth Bracco, and a brother, Salvatore, Jr. Her father was of Italian descent, while her mother was born in England, and had some French ancestry. Her parents met during World War II; Eileen came with Salvatore to the United States as a war bride. Bracco grew up in Hicksville, New York, on Long Island, from fourth grade. Bracco graduated from Hicksville High School in 1972. Career Bracco moved to France in 1974, where she became a fashion model for Jean-Paul Gaultier. She lived there for about a decade.	524384
wiki20220301en020_104649	Lorraine Bracco	Career Bracco moved to France in 1974, where she became a fashion model for Jean-Paul Gaultier. She lived there for about a decade. While still modeling, Bracco was approached by Marc Camoletti, who offered her a major role in the film adaptation of one of his plays, Duos sur canapé (1979). Bracco did not imagine that she could be an actress, and initially refused. She eventually made the film, but found the experience "boring" and her performance "terrible." Nevertheless, she played supporting roles in two other French films "for the money." After one of her friends suggested that she might enjoy acting if she took some training, she took seminars with John Strasberg. Although she loved the lessons, she was still unsure of her talents. During the 1980s, she also worked as a disc jockey for Radio Luxembourg. Also, she appeared as Paul Guilfoyle's hostage in the first season Crime Story episode, "Hide and Go Thief". Her sister Elizabeth played a hostage in the series pilot.	Lorraine Bracco. Career Bracco moved to France in 1974, where she became a fashion model for Jean-Paul Gaultier. She lived there for about a decade. While still modeling, Bracco was approached by Marc Camoletti, who offered her a major role in the film adaptation of one of his plays, Duos sur canapé (1979). Bracco did not imagine that she could be an actress, and initially refused. She eventually made the film, but found the experience "boring" and her performance "terrible." Nevertheless, she played supporting roles in two other French films "for the money." After one of her friends suggested that she might enjoy acting if she took some training, she took seminars with John Strasberg. Although she loved the lessons, she was still unsure of her talents. During the 1980s, she also worked as a disc jockey for Radio Luxembourg. Also, she appeared as Paul Guilfoyle's hostage in the first season Crime Story episode, "Hide and Go Thief". Her sister Elizabeth played a hostage in the series pilot.	524384
wiki20220301en020_104650	Lorraine Bracco	Eventually, Italian director and novelist Lina Wertmüller gave Bracco a small part in the film Camorra. "She dressed me up like an Italian woman of no means. A street woman clad in disheveled clothes, hair unkempt and all that, and threw me on the set. She was so creative. I mean, Lina accentuated my eyes with dark make-up, the way Sophia Loren used to appear in those epic roles in the '60s. And talk about talent. She's so bright and perceptive. I mean, she's just fantastic. And yes, I learned a lot from her. She's a master of her profession, and I've been blessed not only with her, but also with so many masters," recounted Bracco to Daniel Simone during a 2007 interview. The experience inspired Bracco to pursue acting.	Lorraine Bracco. Eventually, Italian director and novelist Lina Wertmüller gave Bracco a small part in the film Camorra. "She dressed me up like an Italian woman of no means. A street woman clad in disheveled clothes, hair unkempt and all that, and threw me on the set. She was so creative. I mean, Lina accentuated my eyes with dark make-up, the way Sophia Loren used to appear in those epic roles in the '60s. And talk about talent. She's so bright and perceptive. I mean, she's just fantastic. And yes, I learned a lot from her. She's a master of her profession, and I've been blessed not only with her, but also with so many masters," recounted Bracco to Daniel Simone during a 2007 interview. The experience inspired Bracco to pursue acting.	524384
wiki20220301en020_104651	Lorraine Bracco	Her other films include Someone to Watch Over Me, Switch, Riding in Cars with Boys, The Basketball Diaries, Medicine Man, Radio Flyer, and Hackers. Bracco was one of many actresses who were considered for the role of Catwoman/Selina Kyle in Tim Burton's film Batman Returns but declined the role. Bracco received her big career break when she was offered the role of mobster wife Karen Hill in Goodfellas, which earned her an Academy Award nomination for Best Supporting Actress and a Golden Globe nomination for Best Supporting Actress – Motion Picture. She won the Los Angeles Film Critics Association Award for Best Supporting Actress and the Chicago Film Critics Association Award for Best Supporting Actress.	Lorraine Bracco. Her other films include Someone to Watch Over Me, Switch, Riding in Cars with Boys, The Basketball Diaries, Medicine Man, Radio Flyer, and Hackers. Bracco was one of many actresses who were considered for the role of Catwoman/Selina Kyle in Tim Burton's film Batman Returns but declined the role. Bracco received her big career break when she was offered the role of mobster wife Karen Hill in Goodfellas, which earned her an Academy Award nomination for Best Supporting Actress and a Golden Globe nomination for Best Supporting Actress – Motion Picture. She won the Los Angeles Film Critics Association Award for Best Supporting Actress and the Chicago Film Critics Association Award for Best Supporting Actress.	524384
wiki20220301en020_104652	Lorraine Bracco	During the audition process for The Sopranos, David Chase wanted Bracco to read for the lead female role of Carmela Soprano. However, Bracco had read the script and was drawn to the part of psychiatrist Jennifer Melfi. Bracco felt so strongly about her ability and desire to play the part that she arranged a meeting with Chase and talked him into letting her have a chance as Melfi. It netted her three consecutive nominations for Outstanding Lead Actress in a Drama Series at the Emmy Awards in 1999, 2000, and 2001, and at the Golden Globe awards for Best TV Actress in a Drama in 2000, 2001, and 2002. She lost out at the Emmys in 1999 and 2001, and at the Golden Globes in 2000 to her co-star Edie Falco. She was nominated again at the 2007 Emmy Awards for Outstanding Supporting Actress in a Drama Series, and thus was pitted against her The Sopranos co-star Aida Turturro for the award.	Lorraine Bracco. During the audition process for The Sopranos, David Chase wanted Bracco to read for the lead female role of Carmela Soprano. However, Bracco had read the script and was drawn to the part of psychiatrist Jennifer Melfi. Bracco felt so strongly about her ability and desire to play the part that she arranged a meeting with Chase and talked him into letting her have a chance as Melfi. It netted her three consecutive nominations for Outstanding Lead Actress in a Drama Series at the Emmy Awards in 1999, 2000, and 2001, and at the Golden Globe awards for Best TV Actress in a Drama in 2000, 2001, and 2002. She lost out at the Emmys in 1999 and 2001, and at the Golden Globes in 2000 to her co-star Edie Falco. She was nominated again at the 2007 Emmy Awards for Outstanding Supporting Actress in a Drama Series, and thus was pitted against her The Sopranos co-star Aida Turturro for the award.	524384
wiki20220301en020_104653	Lorraine Bracco	Bracco is the owner of Bracco Wines, in association with Straight-Up Brands LLC. Her line of wines was featured on the Season 1 finale of Bravo's show Top Chef in 2006. She appeared as a guest judge for the show's two-episode finale and as a special judge on Top Chef: All Stars, in the episode titled "An Offer They Can't Refuse", which featured Italian cuisine. Bracco also appeared on a season 6 episode of Throwdown! with Bobby Flay, as a guest judge for the ravioli throwdown. Beginning in 2016, Bracco had a recurring role as Toni on the Showtime comedy series Dice. From 2017 to 2018, she had a five-episode recurring role as Mayor Margaret Dutton in the CBS police drama series Blue Bloods. In 2020, Bracco starred in the HGTV documentary television series shot in Sambuca di Sicilia, My Big Italian Adventure, and chronicling her 200-year-old, €1 house renovation at Via Guglielmo Marconi. Personal life Bracco has been married and divorced twice.	Lorraine Bracco. Bracco is the owner of Bracco Wines, in association with Straight-Up Brands LLC. Her line of wines was featured on the Season 1 finale of Bravo's show Top Chef in 2006. She appeared as a guest judge for the show's two-episode finale and as a special judge on Top Chef: All Stars, in the episode titled "An Offer They Can't Refuse", which featured Italian cuisine. Bracco also appeared on a season 6 episode of Throwdown! with Bobby Flay, as a guest judge for the ravioli throwdown. Beginning in 2016, Bracco had a recurring role as Toni on the Showtime comedy series Dice. From 2017 to 2018, she had a five-episode recurring role as Mayor Margaret Dutton in the CBS police drama series Blue Bloods. In 2020, Bracco starred in the HGTV documentary television series shot in Sambuca di Sicilia, My Big Italian Adventure, and chronicling her 200-year-old, €1 house renovation at Via Guglielmo Marconi. Personal life Bracco has been married and divorced twice.	524384
wiki20220301en020_104654	Lorraine Bracco	Personal life Bracco has been married and divorced twice. She married Frenchman Daniel Guerard in 1979; they divorced in 1982. They have one daughter, actress Margaux Guerard. She was in a 12-year relationship with actor Harvey Keitel, whom she met while living in Paris. They have one daughter, Stella Keitel (b. 1985). Bracco and Keitel fought a lengthy custody battle over Stella, resulting in Bracco's depression and $2 million in legal fees. Bracco's second marriage was to actor Edward James Olmos in 1994; they divorced in 2002. Bracco is a practitioner of Shotokan Karate. In 2015, she wrote a self-help book, To the Fullest: The Clean Up Your Act Plan to Lose Weight, Rejuvenate, and Be the Best You Can Be. Filmography Film Television Awards and nominations See also List of celebrities who own wineries and vineyards References Bibliography External links Lorraine Bracco at the archive.org copy of the-sopranos.com New York Times interview	Lorraine Bracco. Personal life Bracco has been married and divorced twice. She married Frenchman Daniel Guerard in 1979; they divorced in 1982. They have one daughter, actress Margaux Guerard. She was in a 12-year relationship with actor Harvey Keitel, whom she met while living in Paris. They have one daughter, Stella Keitel (b. 1985). Bracco and Keitel fought a lengthy custody battle over Stella, resulting in Bracco's depression and $2 million in legal fees. Bracco's second marriage was to actor Edward James Olmos in 1994; they divorced in 2002. Bracco is a practitioner of Shotokan Karate. In 2015, she wrote a self-help book, To the Fullest: The Clean Up Your Act Plan to Lose Weight, Rejuvenate, and Be the Best You Can Be. Filmography Film Television Awards and nominations See also List of celebrities who own wineries and vineyards References Bibliography External links Lorraine Bracco at the archive.org copy of the-sopranos.com New York Times interview	524384
wiki20220301en020_104655	Lorraine Bracco	See also List of celebrities who own wineries and vineyards References Bibliography External links Lorraine Bracco at the archive.org copy of the-sopranos.com New York Times interview 1954 births Living people Actresses from New York (state) American expatriates in France New York (state) Democrats Shotokan practitioners American female karateka Female models from New York (state) American film actresses American people of English descent American people of French descent American people of Italian descent American television actresses American voice actresses 20th-century American actresses 21st-century American actresses People from Westbury, New York People from Bay Ridge, Brooklyn	Lorraine Bracco. See also List of celebrities who own wineries and vineyards References Bibliography External links Lorraine Bracco at the archive.org copy of the-sopranos.com New York Times interview 1954 births Living people Actresses from New York (state) American expatriates in France New York (state) Democrats Shotokan practitioners American female karateka Female models from New York (state) American film actresses American people of English descent American people of French descent American people of Italian descent American television actresses American voice actresses 20th-century American actresses 21st-century American actresses People from Westbury, New York People from Bay Ridge, Brooklyn	524384
wiki20220301en020_104656	Megakaryocyte	A megakaryocyte (mega- + karyo- + -cyte, "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases. Owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte.	Megakaryocyte. A megakaryocyte (mega- + karyo- + -cyte, "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but can increase in number nearly 10-fold during the course of certain diseases. Owing to variations in combining forms and spelling, synonyms include megalokaryocyte and megacaryocyte.	524385
wiki20220301en020_104657	Megakaryocyte	Structure In general, megakaryocytes are 10 to 15 times larger than a typical red blood cell, averaging 50–100 μm in diameter. During its maturation, the megakaryocyte grows in size and replicates its DNA without cytokinesis in a process called endomitosis. As a result, the nucleus of the megakaryocyte can become very large and lobulated, which, under a light microscope, can give the false impression that there are several nuclei. In some cases, the nucleus may contain up to 64N DNA, or 32 copies of the normal complement of DNA in a human cell. The cytoplasm, just as the platelets that bud off from it, contains α-granula and dense bodies. Development	Megakaryocyte. Structure In general, megakaryocytes are 10 to 15 times larger than a typical red blood cell, averaging 50–100 μm in diameter. During its maturation, the megakaryocyte grows in size and replicates its DNA without cytokinesis in a process called endomitosis. As a result, the nucleus of the megakaryocyte can become very large and lobulated, which, under a light microscope, can give the false impression that there are several nuclei. In some cases, the nucleus may contain up to 64N DNA, or 32 copies of the normal complement of DNA in a human cell. The cytoplasm, just as the platelets that bud off from it, contains α-granula and dense bodies. Development	524385
wiki20220301en020_104658	Megakaryocyte	The cytoplasm, just as the platelets that bud off from it, contains α-granula and dense bodies. Development Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. They are produced primarily by the liver, kidney, spleen, and bone marrow. These multipotent stem cells live in the marrow sinusoids and are capable of producing all types of blood cells depending on the signals they receive. The primary signal for megakaryocyte production is thrombopoietin or TPO. TPO is sufficient but not absolutely necessary for inducing differentiation of progenitor cells in the bone marrow towards a final megakaryocyte phenotype. Other molecular signals for megakaryocyte differentiation include GM-CSF, IL-3, IL-6, IL-11, chemokines (SDF-1, FGF-4). and erythropoietin. The megakaryocyte develops through the following lineage: CFU-Me (pluripotential hemopoietic stem cell or hemocytoblast) → megakaryoblast → promegakaryocyte → megakaryocyte.	Megakaryocyte. The cytoplasm, just as the platelets that bud off from it, contains α-granula and dense bodies. Development Megakaryocytes are derived from hematopoietic stem cell precursor cells in the bone marrow. They are produced primarily by the liver, kidney, spleen, and bone marrow. These multipotent stem cells live in the marrow sinusoids and are capable of producing all types of blood cells depending on the signals they receive. The primary signal for megakaryocyte production is thrombopoietin or TPO. TPO is sufficient but not absolutely necessary for inducing differentiation of progenitor cells in the bone marrow towards a final megakaryocyte phenotype. Other molecular signals for megakaryocyte differentiation include GM-CSF, IL-3, IL-6, IL-11, chemokines (SDF-1, FGF-4). and erythropoietin. The megakaryocyte develops through the following lineage: CFU-Me (pluripotential hemopoietic stem cell or hemocytoblast) → megakaryoblast → promegakaryocyte → megakaryocyte.	524385
wiki20220301en020_104659	Megakaryocyte	CFU-Me (pluripotential hemopoietic stem cell or hemocytoblast) → megakaryoblast → promegakaryocyte → megakaryocyte. The cell eventually reaches megakaryocyte stage and loses its ability to divide. However, it is still able to replicate its DNA and continue development, becoming polyploid. The cytoplasm continues to expand and the DNA amount can increase up to 64n in humans and 256n in mice. Many of the morphological features of megakaryocyte differentiation can be recapitulated in non-hematopoietic cells by the expression of Class VI β-tubulin (β6) and they provide a mechanistic basis for understanding these changes. Function	Megakaryocyte. CFU-Me (pluripotential hemopoietic stem cell or hemocytoblast) → megakaryoblast → promegakaryocyte → megakaryocyte. The cell eventually reaches megakaryocyte stage and loses its ability to divide. However, it is still able to replicate its DNA and continue development, becoming polyploid. The cytoplasm continues to expand and the DNA amount can increase up to 64n in humans and 256n in mice. Many of the morphological features of megakaryocyte differentiation can be recapitulated in non-hematopoietic cells by the expression of Class VI β-tubulin (β6) and they provide a mechanistic basis for understanding these changes. Function	524385
wiki20220301en020_104660	Megakaryocyte	Platelet release	Megakaryocyte. Platelet release	524385
wiki20220301en020_104661	Megakaryocyte	Once the cell has completed differentiation and become a mature megakaryocyte, it begins the process of producing platelets. The maturation process occurs via endomitotic synchronous replication whereby the cytoplasmic volume enlarges as the number of chromosomes multiplies without cellular division. The cell ceases its growth at 4N, 8N or 16N, becomes granular, and begins to produce platelets. Thrombopoietin plays a role in inducing the megakaryocyte to form small proto-platelet processes. Platelets are held within these internal membranes within the cytoplasm of megakaryocytes. There are two proposed mechanisms for platelet release. In one scenario, these proto-platelet processes break up explosively to become platelets. It is possible to visualize the spontaneous release of platelets using holotomographic live cell imaging. Alternatively, the cell may form platelet ribbons into blood vessels. The ribbons are formed via pseudopodia and they are able to continuously emit	Megakaryocyte. Once the cell has completed differentiation and become a mature megakaryocyte, it begins the process of producing platelets. The maturation process occurs via endomitotic synchronous replication whereby the cytoplasmic volume enlarges as the number of chromosomes multiplies without cellular division. The cell ceases its growth at 4N, 8N or 16N, becomes granular, and begins to produce platelets. Thrombopoietin plays a role in inducing the megakaryocyte to form small proto-platelet processes. Platelets are held within these internal membranes within the cytoplasm of megakaryocytes. There are two proposed mechanisms for platelet release. In one scenario, these proto-platelet processes break up explosively to become platelets. It is possible to visualize the spontaneous release of platelets using holotomographic live cell imaging. Alternatively, the cell may form platelet ribbons into blood vessels. The ribbons are formed via pseudopodia and they are able to continuously emit	524385
wiki20220301en020_104662	Megakaryocyte	platelets using holotomographic live cell imaging. Alternatively, the cell may form platelet ribbons into blood vessels. The ribbons are formed via pseudopodia and they are able to continuously emit platelets into circulation. In either scenario, each of these proto-platelet processes can give rise to 2000–5000 new platelets upon breakup. Overall, 2/3 of these newly produced platelets will remain in circulation while 1/3 will be sequestered by the spleen.	Megakaryocyte. platelets using holotomographic live cell imaging. Alternatively, the cell may form platelet ribbons into blood vessels. The ribbons are formed via pseudopodia and they are able to continuously emit platelets into circulation. In either scenario, each of these proto-platelet processes can give rise to 2000–5000 new platelets upon breakup. Overall, 2/3 of these newly produced platelets will remain in circulation while 1/3 will be sequestered by the spleen.	524385
wiki20220301en020_104663	Megakaryocyte	Thrombopoietin (TPO) is a 353-amino acid protein encoded on chromosome 3p27. TPO is primarily synthesized in the liver but can be made by kidneys, testes, brain, and even bone marrow stromal cells. It has high homology with erythropoietin. It is essential for the formation of an adequate quantity of platelets. After budding off platelets, what remains is mainly the cell nucleus. This crosses the bone marrow barrier to the blood and is consumed in the lung by alveolar macrophages. Effects of cytokines Cytokines are signals used in the immune system for intercellular communication. There are many cytokines that affect megakaryocytes. Certain cytokines such as IL-3, IL-6, IL-11, LIF, erythropoietin, and thrombopoietin all stimulate the maturation of megakaryocytic progenitor cells. Other signals such as PF4, CXCL5, CXCL7, and CCL5 inhibit platelet formation.	Megakaryocyte. Thrombopoietin (TPO) is a 353-amino acid protein encoded on chromosome 3p27. TPO is primarily synthesized in the liver but can be made by kidneys, testes, brain, and even bone marrow stromal cells. It has high homology with erythropoietin. It is essential for the formation of an adequate quantity of platelets. After budding off platelets, what remains is mainly the cell nucleus. This crosses the bone marrow barrier to the blood and is consumed in the lung by alveolar macrophages. Effects of cytokines Cytokines are signals used in the immune system for intercellular communication. There are many cytokines that affect megakaryocytes. Certain cytokines such as IL-3, IL-6, IL-11, LIF, erythropoietin, and thrombopoietin all stimulate the maturation of megakaryocytic progenitor cells. Other signals such as PF4, CXCL5, CXCL7, and CCL5 inhibit platelet formation.	524385
wiki20220301en020_104664	Megakaryocyte	Clinical significance Megakaryocytes are directly responsible for producing platelets, which are needed for the formation of a thrombus, or blood clot. There are several diseases that are directly attributable to abnormal megakaryocyte function or abnormal platelet function. Essential thrombocytosis	Megakaryocyte. Clinical significance Megakaryocytes are directly responsible for producing platelets, which are needed for the formation of a thrombus, or blood clot. There are several diseases that are directly attributable to abnormal megakaryocyte function or abnormal platelet function. Essential thrombocytosis	524385
wiki20220301en020_104665	Megakaryocyte	Essential thrombocytosis (ET), also known as essential thrombocythemia, is a disorder characterized by elevated numbers of circulating platelets. The disease occurs in 1–2 per 100,000 people. The 2016 WHO requirements for diagnosis include > 450,000 platelets/μL of blood (normal 150,000–400,000) and a bone marrow biopsy. Some of the consequences of having such high numbers of platelets include thrombosis or clots throughout the body. Thrombi form more frequently in arteries than veins. It seems ironic that having platelet counts above 1,000,000 platelets/μL can lead to hemorrhagic events. Recent evidence suggests that the majority of ET cases are due to a mutation in the JAK2 protein, a member of the JAK-STAT pathway. Evidence suggests that this mutation renders the megakaryocyte hypersensitive to thrombopoietin and causes clonal proliferation of megakaryocytes. There is a significant risk of transformation to leukemia with this disorder. The primary treatment consists of anagrelide	Megakaryocyte. Essential thrombocytosis (ET), also known as essential thrombocythemia, is a disorder characterized by elevated numbers of circulating platelets. The disease occurs in 1–2 per 100,000 people. The 2016 WHO requirements for diagnosis include > 450,000 platelets/μL of blood (normal 150,000–400,000) and a bone marrow biopsy. Some of the consequences of having such high numbers of platelets include thrombosis or clots throughout the body. Thrombi form more frequently in arteries than veins. It seems ironic that having platelet counts above 1,000,000 platelets/μL can lead to hemorrhagic events. Recent evidence suggests that the majority of ET cases are due to a mutation in the JAK2 protein, a member of the JAK-STAT pathway. Evidence suggests that this mutation renders the megakaryocyte hypersensitive to thrombopoietin and causes clonal proliferation of megakaryocytes. There is a significant risk of transformation to leukemia with this disorder. The primary treatment consists of anagrelide	524385
wiki20220301en020_104666	Megakaryocyte	to thrombopoietin and causes clonal proliferation of megakaryocytes. There is a significant risk of transformation to leukemia with this disorder. The primary treatment consists of anagrelide or hydroxyurea to lower platelet levels.	Megakaryocyte. to thrombopoietin and causes clonal proliferation of megakaryocytes. There is a significant risk of transformation to leukemia with this disorder. The primary treatment consists of anagrelide or hydroxyurea to lower platelet levels.	524385