Botulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromuscular junction and thus causes flaccid paralysis. Infection with the bacterium causes the disease botulism; the toxin is used commercially for medical and cosmetic purposes. There are seven main types of botulinum toxin, named type A–G. New types are found. Types A and B are capable of causing disease in humans, are used commercially and medically. Types C–G are less common. Botulinum toxin types B are used in medicine to treat various muscle spasms. Botulinum toxin is the most acutely lethal toxin known. Intoxication can occur as a result of either wound or intestinal infection or by ingesting preformed toxin in food; the estimated human median lethal dose of type A toxin is 1.3–2.1 ng/kg intravenously or intramuscularly, 10–13 ng/kg when inhaled, or 1000 ng/kg when taken by mouth. Commercial forms are marketed under the brand names Botox, Dysport/Azzalure, Xeomin/Bocouture, Jeuveau.
Botulinum toxin is used to treat a number of therapeutic indications, many of which are not part of the approved drug label. Botulinum toxin is used to treat a number of disorders characterized by overactive muscle movement, including post-stroke spasticity, post-spinal cord injury spasticity, spasms of the head and neck, vagina, limbs and vocal cords. Botulinum toxin is used to relax clenching of muscles, including those of the oesophagus, lower urinary tract and bladder, or clenching of the anus which can exacerbate anal fissure, it may be used for improper eye alignment. Botulinum toxin appears to be effective for refractory overactive bladder. Strabismus is caused by imbalances in the actions of muscles that rotate the eyes, can sometimes be relieved by weakening a muscle that pulls too or pulls against one, weakened by disease or trauma. Muscles weakened by toxin injection recover from paralysis after several months, so it might seem that injection would need to be repeated. However, muscles adapt to the lengths at which they are chronically held, so that if a paralyzed muscle is stretched by its antagonist, it grows longer, while the antagonist shortens, yielding a permanent effect.
If there is good binocular vision, the brain mechanism of motor fusion, which aligns the eyes on a target visible to both, can stabilize the corrected alignment. In January 2014, botulinum toxin was approved by UK's Medicines and Healthcare Products Regulatory Agency for treatment of restricted ankle motion due to lower limb spasticity associated with stroke in adults. On 29 July 2016, the U. S. Food and Drug Administration approved abobotulinumtoxinA for injection for the treatment of lower limb spasticity in pediatric patients two years of age and older. AbobotulinumtoxinA is the first and only FDA-approved botulinum toxin for the treatment of pediatric lower limb spasticity. In the United States of America, the FDA approves the text of the labels of prescription medicines; the FDA approves. However, those approved by the FDA to prescribe these drugs may prescribe them for any condition they wish, called off-label use. Botulinum toxins have been used off-label for several pediatric conditions, including infantile esotropia.
BTX-A has been approved for the treatment of excessive underarm sweating of unknown cause, which cannot be managed by topical agents. In 2010, the U. S. Food and Drug Administration approved intramuscular botulinum toxin injections for prophylactic treatment of chronic migraine headache. In cosmetic applications, botulinum toxin is considered safe and effective for reduction of facial wrinkles in the uppermost third of the face. Commercial forms are marketed under the brand names Botox Cosmetic/Vistabel from Allergan, Dysport/Azzalure from Galderma and Ipsen, Xeomin/Bocouture from Merz, in the US only, Jeuveau from Evolus, manufactured by Daewoong; the effects of current botulinum toxin injections for glabellar lines last two to four months and in some cases, product-dependent, with some patients experiencing a longer duration of effect. Injection of botulinum toxin into the muscles under facial wrinkles causes relaxation of those muscles, resulting in the smoothing of the overlying skin. Smoothing of wrinkles is visible three-five days after injection, with maximum effect a week following injection.
Muscles can be treated to maintain the smoothed appearance. Botulinum toxin is used to treat disorders of hyperactive nerves including excessive sweating, neuropathic pain, some allergy symptoms. In addition to these uses, botulinum toxin is being evaluated for use in treating chronic pain. Studies show that botulinum toxin may be injected into arthritic shoulder joints to reduce chronic pain and improve range of motion. While botulinum toxin is considered safe in a clinical setting, there can be serious side effects from its use. Most botulinum toxin can be injected into the wrong muscle group or with time spread from the injection site, causing paralysis of unintended muscles. Side effects from cosmetic use result from unintended paralysis of facial muscles; these include partial facial paralysis, muscle weakness, trouble swallowing. Side effects are not limited to direct paralysis however, can include headaches, flu-like symptoms, allergic reactions. Just as cosmetic
Adapter molecule crk known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene. The CRK protein participates in the Reelin signaling cascade downstream of DAB1. Adapter molecule crk is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins; this protein has several SH2 and SH3 domains and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described. Crk together with CrkL participates in the Reelin signaling cascade downstream of DAB1.v-Crk, a transforming oncoprotein from avian sarcoma viruses, is a fusion of viral "gag" protein with the SH2 and SH3 domains of cellular Crk.
The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from, isolated a protein, lacking kinase domains, but capable of stimulating phosphorylation of tyrosines in cells. Crk should not be confused with Src, which has cellular and viral forms and is involved in some of the same signaling pathways but is a protein tyrosine-kinase. CRK has been shown to interact with: CrkL, "Crk-like" protein Crk Info with links in the Cell Migration Gateway Proto-Oncogene+Proteins+c-crk at the US National Library of Medicine Medical Subject Headings Oncogene+Protein+v-crk at the US National Library of Medicine Medical Subject Headings Human CRK genome location and CRK gene details page in the UCSC Genome Browser
Gleaston Castle is a medieval building in a valley about 1 kilometre north-east of the village of Gleaston. The village lies between the towns of Ulverston and Barrow-in-Furness in the Furness peninsula, England. Gleaston Castle has a quadrilateral plan, with a tower at each corner; the largest of these, the north-west tower housed a hall. The castle was most built for John Harington, 1st Baron Harington in the 14th century, replacing nearby Aldingham Motte. Gleaston Castle descended through the Harrington family until 1458 when it passed to William Bonville through marriage and was subsequently abandoned; the castle passed to the Grey family until Henry Grey, 1st Duke of Suffolk was executed for treason in 1554. As a result, Gleaston Castle became royal property before it was bought by the Preston family in the 17th century, passed to the Cavendish family; as the castle was disused from the mid-15th century it fell into dilapidation, antiquarian depictions from the 18th century show Gleaston in a state of ruin.
Though it is not open to the public, it has been the subject of historical and archaeological investigation in the 20th and 21st centuries. From the 12th century the manor of Muchland was administered from Aldingham Castle. Muchland became known as Aldingham manor and in 1291 it came into the ownership of the Harrington family. In the 14th century, the Scots attacked the Furness peninsula during the Scottish Wars of Independence; these factors may have led to the Harrington family abandoning Aldingham and establishing the administrative centre of the manor at the newly built Gleaston Castle, though the construction work could have been the result of their growing social status, they may have needed more room for a greater number of servants. The castle was built for John Harington, 1st Baron Harington. Gleaston Castle is first mentioned in 1389, although John Harington, 2nd Baron Harington is said to have died there in 1363. In 1415 John Harington was granted a papal indult for a private chapel and a portable altar for mass.
It is however, that the castle would have had its own chapel before this date. The Harington family owned Gleaston Castle until William Harington, 5th Baron Harington died in 1458; the castle and barony passed to William Bonville, 6th Baron Harington through marriage. He died in 1460 and the castle passed to Thomas Grey, 1st Marquess of Dorset, again through marriage, it is that around this time Gleaston Castle was abandoned. In 1540, the antiquarian John Leland noted "there is a ruine and waulles of a castell in Lancaster-shire cawlyd Gleston Castell sometyme longinge to Lord Harrington now to the Marquis of Dorset", other antiquarians provided descriptions of the site; when Henry Grey, 1st Duke of Suffolk was executed for treason in 1554 his property was taken over by the monarch. In 1671 Thomas Preston, 3rd Baronet Preston bought Aldingham manor; the property descended through the Prestons to the Cavendish family. The castle is now part of an active farm; the farm buildings incorporate some of the fabric of the castle.
The Prestons owned the castle until 1922. According to a 1905 document from the Cumbria Archive Centre up to four human skeletons were discovered at the castle in the 19th century when the farm buildings were built. An engraving by Samuel and Nathaniel Buck from 1727 is one of the earliest depictions of the castle, with depictions from antiquarian William Close, artist William Green, Edwin Waugh; the Buck brother’s engraving showed the castle in a state of ruin, Waugh's depiction in particular shows that from the mid-19th century the castle has remained in a similar state of ruin until the present. Gleaston Castle is now a Grade I listed ruin, a scheduled monument; the ruins can be viewed from the roadside, but it is unsafe to enter the castle due to its state of repair. As of 2016, the castle is on Historic England's Heritage At Risk register and its condition is described as "very bad" and "deteriorating". Since the late 20th century there have been efforts to preserve the site: in 1998 the Lancaster University Archaeological Unit conducted an assessment of the standing building for further research and whether it would be possible to open the building to the public, but Historic England notes that "no agreement was reached regarding a scheme of consolidation"The castle's precarious condition meant that the structure was not recorded until 2015, when the Morecambe Bay Partnership with funding from the Castle Studies Trust commissioned Greenlane Archaeology to carry out an aerial survey of the site.
As well as producing a visual record of the castle from which elevations and plans could be derived, it identified features within the castle which could be buildings which no longer survive. In 2016 the University of Central Lancashire undertook a geophysical survey, using it as training for archaeology students and volunteers; the survey indicated there was a garden to the north of the castle, timber structures within the castle. Gleaston Castle was abandoned around a century after its construction; as a result, the standing remains are an example of 14th-century architecture which has not been adapted by occupation. The remains consist of limestone, quarried locally, while sandstone was used for doors and windows; the sandstone may have been recovered from a beach 2 miles from the castle as there is no local source of sandstone. This method of using red sandstone for architectural details can be seen at Piel Castle near Barrow-in-Furness; the castle was a walled en
Rede Globo is a Brazilian television network, owned by the media conglomerate Grupo Globo, it was founded on April 26, 1965 by Roberto Marinho. Ilusões Perdidas was the first telenovela produced by the network. Indicates the winner of the Troféu Imprensa for Best Telenovela. À Sombra dos Laranjais Locomotivas Dona Xepa Espelho Mágico Nina Sem Lenço, Sem Documento Sinhazinha Flô O Astro O Pulo do Gato Maria, Maria Te Contei? Dancin' Days Gina Sinal de Alerta Pecado Rasgado A Sucessora Pai Herói Memórias de Amor Feijão Maravilha Cabocla Marron Glacê Os Gigantes Olhai os Lírios do Campo Marina Água Viva Chega Mais Coração Alado Plumas e Paetês As Três Marias Baila Comigo O Amor É Nosso Ciranda de Pedra Brilhante Jogo da Vida Terras do Sem-Fim Sétimo Sentido Elas por Elas O Homem Proibido Paraíso Sol de Verão Final Feliz Pão Pão, Beijo Beijo Louco Amor Guerra dos Sexos Eu Prometo Voltei pra Você Champagne Transas e Caretas Amor com Amor Se Paga Partido Alto Vereda Tropical Livre para Voar Corpo a Corpo Um Sonho a Mais A Gata Comeu Roque Santeiro Ti Ti Ti De Quina pra Lua Selva de Pedra Cambalacho Sinhá Moça Roda de Fogo Hipertensão Direito de Amar O Outro Brega & Chique Expresso Brasil Bambolê Mandala Sassaricando Fera Radical Vale Tudo Bebê a Bordo Vida Nova O Salvador da Pátria Que Rei Sou Eu?
Pacto de Sangue Tieta Top Model O Sexo dos Anjos Paraíso Tropical Eterna Magia Sete Pecados Duas Caras Desejo Proibido Beleza Pura Ciranda de Pedra A Favorita Três Irmãs Negócio da China Caminho das Índias Paraíso Caras & Bocas Viver a Vida Cama de Gato List of 8/9 PM telenovelas of Rede Globo List of 11 PM telenovelas of Rede Globo
CAMP, is one of the world's leading manufacturers of equipment for climbing and associated activities such as ski mountaineering and industrial safety. The company is based in Italy. CAMP manufactures a wide range of products, including ice axes, ice screws, carabiners, tricams, camming devices, helmets, tents, ski racing clothing, various snow tools; the company was founded by Nicola Codega, a blacksmith, in 1889 in the Italian alpine village of Premana, where it is still based. Producing wrought-iron goods, an order in 1920 for ice axes for the Italian army was their first foray into the world of climbing equipment. From there the company extended its climbing range to include crampons and nuts, with the encouragement of leading mountaineer Riccardo Cassin and collaboration with American climber Greg Lowe, into non-metallic equipment; the company is still run by Codega's descendants. CAMP website
The 2012 FIA GT3 European Championship was the seventh season of the FIA GT3 European Championship. The season ended on 23 September at the Nürburgring; the season featured six double-header rounds, with each race lasting for a duration of 60 minutes. Most of the events were support races to the 2012 FIA GT1 World Championship. On 2 April 2012, the SRO announced the final calendar for 2012; the entry list was published by the FIA on 3 April 2012. For the combined races with the FIA GT1 World Championship, GT3 cars ran with 100 in front of their usual car numbers. Championship points will be awarded to the first ten positions in each race. Entries must complete 75% of the winning car's race distance in order to be classified and earn points. Individual drivers are required to participate for a minimum of 25 minutes in order to earn championship points in any race. Teams must have two cars at a race weekend in order to be eligible for scoring points in the Teams' Championship. If a team with just one car finishes in a points position, the cars of the teams that finished below get the extra points.
As well as this, Esta Motorsports did not accrue points for their one-off appearance at the Moscow event, nor did Team Novadriver for their expanded two-car entry at the Nürburgring. Official Website of the FIA GT3 European Championship