Ketone bodies are the water-soluble molecules containing the ketone group that are produced by the liver from fatty acids during periods of low food intake, carbohydrate restrictive diets, prolonged intense exercise, alcoholism, or in untreated type 1 diabetes mellitus. Ketone bodies are transported into tissues outside the liver and converted into acetyl-CoA, which enters the citric acid cycle and is oxidized in the mitochondria for energy. In the brain, ketone bodies are used to make acetyl-CoA into long-chain fatty acids. Ketone bodies are produced by the liver under the circumstances listed above, resultant of intense gluconeogenesis, the production of glucose from non-carbohydrate sources, they are therefore always released into the blood by the liver together with newly produced glucose after the liver glycogen stores have been depleted. When two acetyl-CoA molecules lose their -CoAs, they can form a dimer called acetoacetate. Β-hydroxybutyrate is a reduced form of acetoacetate, in which the ketone group is converted into an alcohol group.

Both are 4-carbon molecules that can be converted back into acetyl-CoA by most tissues of the body, with the notable exception of the liver. Acetone is the decarboxylated form of acetoacetate which cannot be converted back into acetyl-CoA except via detoxification in the liver where it is converted into lactic acid, which can, in turn, be oxidized into pyruvic acid, only into acetyl-CoA. Ketone bodies have a characteristic smell, which can be detected in the breath of persons in ketosis and ketoacidosis, it is described as fruity or like nail polish remover. Apart from the three endogenous ketone bodies, other ketone bodies like β-ketopentanoate and β-hydroxypentanoate may be created as a result of the metabolism of synthetic triglycerides, such as triheptanoin. Fats stored in adipose tissue are released from the fat cells into the blood as free fatty acids and glycerol when insulin levels are low and glucagon and epinephrine levels in the blood are high; this occurs between meals, during fasting and strenuous exercise, when blood glucose levels are to fall.

Fatty acids are high energy fuels and are taken up by all metabolizing cells that have mitochondria. This is. Red blood cells do not contain mitochondria and are therefore dependent on anaerobic glycolysis for their energy requirements. In all other tissues, the fatty acids that enter the metabolizing cells are combined with coenzyme A to form acyl-CoA chains; these are transferred into the mitochondria of the cells, where they are broken down into acetyl-CoA units by a sequence of reactions known as β-oxidation. The acetyl-CoA produced by β-oxidation enters the citric acid cycle in the mitochondrion by combining with oxaloacetate to form citrate; this results in the complete combustion of the acetyl group of acetyl-CoA to water. The energy released in this process is captured in the form of 1 GTP and 11 ATP molecules per acetyl group oxidized; this is the fate of acetyl-CoA wherever β-oxidation of fatty acids occurs, except under certain circumstances in the liver. In the liver oxaloacetate is wholly or diverted into the gluconeogenic pathway during fasting, starvation, a low carbohydrate diet, prolonged strenuous exercise, in uncontrolled type 1 diabetes mellitus.

Under these circumstances oxaloacetate is hydrogenated to malate, removed from the mitochondrion to be converted into glucose in the cytoplasm of the liver cells, from where the glucose is released into the blood. In the liver, oxaloacetate is unavailable for condensation with acetyl-CoA when significant gluconeogenesis has been stimulated by low insulin and high glucagon concentrations in the blood. Under these circumstances, acetyl-CoA is diverted to the formation of acetoacetate and beta-hydroxybutyrate. Acetoacetate, beta-hydroxybutyrate, their spontaneous breakdown product, are known as ketone bodies; the ketone bodies are released by the liver into the blood. All cells with mitochondria can take ketone bodies up from the blood and reconvert them into acetyl-CoA, which can be used as fuel in their citric acid cycles, as no other tissue can divert its oxaloacetate into the gluconeogenic pathway in the way that the liver does this. Unlike free fatty acids, ketone bodies can cross the blood-brain barrier and are therefore available as fuel for the cells of the central nervous system, acting as a substitute for glucose, on which these cells survive.

The occurrence of high levels of ketone bodies in the blood during starvation, a low carbohydrate diet and prolonged heavy exercise can lead to ketosis, in its extreme form in out-of-control type 1 diabetes mellitus, as ketoacidosis. Acetoacetate has a characteristic smell, for the people who can detect this smell, which occurs in the breath and urine during ketosis. On the other hand, most people can smell acetone, whose "sweet & fruity" odor characterizes the breath of persons in ketosis or ketoacidosis. Ketone bodies can be utilized as fuel in the heart and muscle, but not the liver, they yield 2 guanosine triphosphate and 22 adenosine triphosphate molecules per acetoacetate molecule when oxidized in the mitochondria. Ketone bodies are transported from the liver to other ti

Knockholt is a village and civil parish in the Sevenoaks District of Kent, lying 5 miles south of Orpington and 3 miles northwest of Sevenoaks. It has a long border with Greater London; some 1,222 people are recorded as lived in the parish at the 2011 Census showing a decennial rise from 1,166. The village is a ribbon development, surrounded by fields that are a part of the Green Belt. There is mixed arable farming, it is in a hilly, rural location, on the top of the dip slope of the North Downs, has views over London. The village name has the unusually late, mid-19th century more common spelling Nockholt, is one of many villages in England with a derivation from oak trees, most a strong departure from today's spelling of oak such as Aike; the village's name is derived from the Anglo-Saxon āc-holt meaning "oak copse". Knockholt was included in Orpington Urban District in 1934; when Greater London was created in 1965, as part of Orpington UD, Knockholt was included in the London Borough of Bromley.

On 1 April 1969, following a concerted campaign by villagers it was removed from the Borough and returned to Kent, being included in Sevenoaks Rural District. The area of the parish is unchanged since first drawn in the late medieval period; when it temporarily merged into Orpington and fell under Bromley Rural District, it was 1701 acres, 18 more than in 1848. The Ivy Farm Communications Centre at Knockholt Pound was the Radio Intercept Station for the non-Morse radio traffic, known as Fish, decoded by Bletchley Park during World War II; the importance of the station is noted in Paul Gannon's book. There are two parts to the village, near the church and school and The Pound, near the Three Horseshoes pub, village shop and garage. There are the Harrow and Tally Ho, as well as a village club. St Katharine's Church, is the Anglican parish church. Near Knockholt Pound is the London Road Evangelical Church, built in the late 19th century as a Methodist chapel, its registration on behalf of the denomination was cancelled in July 1967, in August 1968 it was re-registered for Evangelical use.

Opposite the parish church is St Katharine's Church of England Primary School. Knockholt railway station sits 2 miles north of the village on the old A21 near Halstead and Badgers Mount and is just within Greater London. Three buses serve the village: the Transport for London services R5 and R10 in a loop from Knockholt to Orpington, the Go-Coach Bus 431 to Sevenoaks and Orpington; until 23 July 2017, Arriva ran the 402 bus route through Knockholt, but cut the service due to low passenger numbers. Knockholt residents host a village carnival every two years, the most recent being in July 2018, a fireworks night every year, late October to early November. Funds raised through these and other events go to local charities. A new regular event in the village is the Knockstock music festival, starting in July 2013 and with plans to run in alternating years when the carnival is not operating. Knockholt Amateur Theatrical Society produce one pantomime every year; this charitable society was formed in 1945.

Kytens is the local youth. There are many other groups including Bowls, Tennis, Horse Riding, Christian Fellowship; this is a popular area for horse riders, walkers and cyclists, due to its beauty. Knockholt Cricket Club completed the 2009 season unbeaten in the Kent County Village League Division 3, believed to be a KCVL first. List of places of worship in Sevenoaks St Katharine's Church Knockholt Parish 360° Panorama of Knockholt Pound Knockholt Carnival website

The Battle of Reynogüelén was a battle between Spanish conquistadors and Mapuche soldiers, thought to have occurred near the confluence of the Ñuble and Itata Rivers, in Chile. This battle is an antecedent of the Arauco War. Diego de Almagro after reaching the Mapocho Valley in 1536, sent Gómez de Alvarado with an expedition of 200 Spaniards, 100 Cavalry and 100 foot, with a large group of Indian auxiliaries to the south of Chile with the mission of exploring the country to the Strait of Magellan; the group advanced without encountering much resistance from the Promaucaes. After crossing the Itata River they were intercepted by a numerous contingent of Mapuches as many as 24,000, armed with many bows and pikes; the Mapuches launched a number of assaults which were repulsed by the Spanish. Frustrated by these reverses and by disorientation caused by the horses, iron weapons, armour of the conquistadors, the natives retreated, leaving many dead and more than one hundred prisoners; the Spanish lost only two men but others were hurt.

Discouraged by the ferocity of the Mapuches, the apparent lack of gold and silver in these lands, Gómez de Alvarado decided to return and inform Almagro what had happened. This battle had a strong influence on Almagro's entire expedition, motivated, in part, its full retreat the following year to Peru. de Góngora Marmolejo, Alonso,Historia de Todas las Cosas que han Acaecido en el Reino de Chile y de los que lo han gobernado, University of Chile: Document Collections in complete texts: Cronicles Cap. II. De cómo el adelantado don Diego de Almagro vino al descubrimiento de Chile y por dónde se descubrió Mariño de Lobera, Pedro,Crónica del Reino de Chile, escrita por el capitán Pedro Mariño de Lobera....reducido a nuevo método y estilo por el Padre Bartolomé de Escobar. Edición digital a partir de Crónicas del Reino de Chile Madrid, Atlas, 1960, pp. 227-562. Biblioteca Virtual Miguel de Cervantes Capítulo VI De la entrada...... Gómez de Alvarado......descubrir lo que había en la Tierra adentro y de una sangrienta batalla que tuvo con los bárbaros Carvallo y Goyeneche, Descripcion Histórico Geografía del Reino de Chile, University of Chile: Document Collections in complete texts: Cronicles Tomo I, Capítulo I.

Descubrimiento de Chile i entrada de los españoles en él

Cornelia Cnoop or Cnopp was a Netherlandish miniature painter. A painting attributed to her hand was exhibited in 1902 in Bruges during the Exposition des primitifs flamands à Bruges, in the Provinciaal Hof as catalog number 130, she was married to Gerard David. She was born in Bruges as the daughter of the goldsmith Jacob Cnoop de Jongere and Kathelijne uter Vorst, her father was a dean of the goldsmiths' guild. She married Gerard David in 1497, they had a daughter Barbara. In 1509 her husband donated a Virgo inter Virgines to the church of the Carmelites, that included a self-portrait on the left and a portrait of his wife on the right. Cornelia Cnoop in Bénézit

Miranda Cosgrove is an American actress and singer-songwriter. Her career began at the age of three, her film debut came in 2003. She appeared in a number of minor television roles over several years before coming to prominence as Megan Parker on the Nickelodeon TV series Drake & Josh. A few years she landed the role of Carly Shay, the lead character in the Nickelodeon TV series iCarly; as of May 2010, Cosgrove earned $180,000 per episode of iCarly, making her the second-highest-paid child star on television. She was listed in the 2012 edition of Guinness World Records as the highest paid child actress for iCarly. Following the success of iCarly, a soundtrack album was released in June 2008, in which she performed four songs, her debut album, Sparks Fly, was released on April 27, 2010. Miranda Cosgrove discography Miranda Cosgrove filmography

Suicide in Romania is a social and health issue. Annually, between 2500-3500 Romanians commit suicide. 72.5% of fatal suicides are the result of hanging. Other methods are each chosen by under 10%. Since 2000, suicides rates have declined in the country. According to the World Bank, the suicide mortality rate has dropped from 13.2 per 100,000 in 2000, to 10.4 per 100,000 in 2016. Research conducted by the World Health Organisation found that Romania had the 103rd highest rate of suicide in the world, on par with China; the rate of suicide among men is higher than among women in Romania. Suicide mortality for men stood at 13.9 per 100,000 in 2016. In contrast, the suicide mortality rate for Romanian women was 2.4 per 100,000. Sorin Rădulescu, “Evoluții și tendințe ale fenomenului suicidar în România, în perioada 1996-2012”, in Revista română de sociologie, new series, year XXV, nr. 3–4, p. 175–202, Bucharest, 2014