title: Flight engineer

text: FEs are also responsible for preflight and postflight aircraft inspections, and ensuring that the weight and balance of the aircraft is correctly calculated to ensure the centre of gravity is within limits. On airplanes where the FE's station is located on the same flight deck just aft of the two pilots (all western three- and four-man deck airplanes), they also monitor an aircraft's flight path, speed, and altitude. A significant portion of their time is spent cross checking pilot selections. The FE is the systems expert of the airplane with an extensive mechanical and technical knowledge of aircraft systems and aircraft performance. On some military airplanes (Lockheed C-5 Galaxy, Boeing E-3 Sentry, McDonnell Douglas KC-10) the FE sits behind the co-pilot in the cockpit, facing outboard to operate a panel of switches, gauges and indicators or forward to operate throttles, lighting controls, flight controls. On the Tupolev Tu-134 the FE sits in the nose of the aircraft. On other western military airplanes, such as on the Lockheed P-3 Orion and Lockheed C-130H Hercules, FEs sit between, slightly aft of (and, in the case of the C-130A-H models, slightly higher than) the pilots. On the P-3 Orion, E-6B Mercury and E-3 Sentry the FE is responsible for starting and shutting down engines at the start and end of each flight, and also during in-flight shutdowns which are carried out to save fuel on long range operations. In some militaries, the aircraft's FE is also authorised to make and certify repairs to the aircraft when it is away from its base. This can eliminate the need for technical repair crews to accompany the aircraft on short deployments.


title: Flight engineer

text: On civilian airplanes the FE is positioned so that they can monitor the forward instruments, pilot selections and adjust the thrust levers located on the centre pedestal; the FE's chair can travel forward and aft and it can swivel laterally 90 degrees, which enables them to face forward and set the engine power, then move aft and rotate sideways to monitor and set the systems panel. The FE is the aircraft systems expert onboard and responsible for troubleshooting and suggesting solutions to in-flight emergencies and abnormal technical conditions, as well as computing takeoff and landing data. The FE's seat on modern aircraft has a complete range of motion (side to side, forward to aft, swivel, up and down) to accommodate the many positions required to monitor and operate the aircraft systems.


title: Flight engineer

text: The basic philosophy of a three-person flight deck in many flight operations, should an abnormality or emergency arise, is for the captain to hand over the actual flying of the aircraft to the first officer (co-pilot). The captain and FE together review and carry out the necessary actions required to contain and rectify the problem. This spreads the workload and ensures a system of cross-checking which maximizes safety. The captain is the manager and decision maker (pilot not flying, PNF), the first officer, or co-pilot, is the actual flier of the aircraft (pilot flying, PF), and the FE reads the check-lists and executes actions required under the auspices of the captain. There can be occasions when the roles of the pilots during an emergency are reversed, i.e. the copilot becomes the PNF and the captain becomes the PF; one such example was on the A300 B-Series aircraft when there was a complete loss of generator-supplied electrical power, whereupon the standby instruments that were powered were on the captain's side only, requiring the captain to be PF and the PNF and FE to resolve the issue.


title: Flight engineer

text: During World War II many U.S. bomber aircraft incorporated a flight engineer's position. However, this position also doubled as a gunner, usually operating the upper turret, as was the case of the Boeing B-17 Flying Fortress. On some commercial airliners with a flight engineer, the FE is the third in command, after the captain and first officer.


title: Flight engineer

text: Unlike commercial pilots, the Federal Aviation Administration never set a mandatory retirement age for flight engineers. As a result, some pilots would voluntarily downgrade themselves when turning 60. This policy was the subject of two U.S. Supreme Court cases in 1985, when it ruled against Western Airlines that forced retirement of flight engineers based on the regulations for pilots was a violation of the Age Discrimination in Employment Act. Earlier in the year it had rejected a policy that prevented pilots from "bumping" flight engineers from their positions upon the former reaching retirement age.


title: Flight engineer

text: Starting in the 1980s, the development of powerful and small integrated circuits and other advances in computers and digital technology eliminated the need for flight engineers on airliners and many modern military aircraft.


title: Flight engineer

text: On two-pilot flight deck airplanes, sensors and computers monitor and adjust systems automatically. There is no onboard technical expert and third pair of eyes. If a malfunction, abnormality or emergency occurs, it is displayed on an electronic display panel. One pilot does the flying while the other pilot starts reading and executing the quick reference handbook (QRH) to resolve the problem. Modern technological advancements in today's aircraft have reduced the dependence upon human control over systems.


title: Flight engineer

text: The most recent aircraft built with FE stations include military variants of the Boeing 707, such as the E-3 Sentry and E-6 Mercury, both built through 1991, the Tupolev Tu-154, the final example of which was delivered in 2013, and the Scaled Composites Stratolaunch whose sole example first flew in 2019. The last major US passenger airline to fly aircraft equipped with a flight engineer's station was Northwest Airlines, who retired their final 747-200s from charter service in 2009. The final major cargo operator to employ flight engineers was FedEx Express when they retired the last of their 727s in 2013. Though FedEx continues to operate the DC-10 as of 2022, all of which were originally delivered with a flight engineer's station, all examples remaining in the fleet have been converted to MD-10 standard, which provides for a two-crew cockpit.


title: Protea

text: Protea () is a genus of South African flowering plants, also called sugarbushes (Afrikaans: "suikerbos").


title: Protea

text: The genus "Protea" was named in 1735 by Carl Linnaeus, possibly after the Greek god Proteus, who could change his form at will, possibly because they have such a wide variety of forms. Linnaeus's genus was formed by merging a number of genera previously published by Herman Boerhaave, although precisely which of Boerhaave's genera were included in Linnaeus's "Protea" varied with each of Linnaeus's publications.


title: Protea

text: The family Proteaceae to which "Protea" species belong is an ancient one among angiosperms. Evidence from pollen fossils suggests Proteaceae ancestors grew in Gondwana, in the Upper Cretaceous, 75–80 million years ago. The Proteaceae are divided into two subfamilies: the Proteoideae, best represented in southern Africa, and the Grevilleoideae, concentrated in Australia and South America and the other smaller segments of Gondwana that are now part of eastern Asia. Africa shares only one genus with Madagascar, whereas South America and Australia share many common genera – this indicates they separated from Africa before they separated from each other.


title: Protea

text: Most proteas occur south of the Limpopo River. However, "Protea caffra kilimandscharica "is found in the chaparral zone of Mount Kenya National Park. About 92% of the species occurs only in the Cape Floristic Region, a narrow belt of mountainous coastal land from Clanwilliam to Grahamstown, South Africa. The extraordinary richness and diversity of species characteristic of the Cape flora are thought to be caused in part by the diverse landscape, where populations can become isolated from each other and in time develop into separate species.


title: Protea

text: Proteas attracted the attention of botanists visiting the Cape of Good Hope in the 17th century. Many species were introduced to Europe in the 18th century, enjoying a unique popularity at the time amongst botanists.


title: Protea

text: Proteas are currently cultivated in over 20 countries. Cultivation is restricted to Mediterranean and subtropical climates. Three categories of traits have to be considered before developing a new cultivar. The yield or production capacity of the cultivar must be considered. The ease of handling and packaging of the cut stems and the last category is to consider the perceived market value of the cultivar The cultivation of a "Protea "plant is time-consuming, so good planning when developing the cross combinations and goals are of great importance of the breeding programme. Some protea flower species, like the king protea flower, are self-pollinating flowers. Other protea species, however, such as "P. cordata", "P. decurrens", and "P. scabra" are self-incompatible, thus rely on cross-pollination for successive seed set. The main vectors responsible for the transfer of pollen in protea cultivation are birds, insects, and wind. Some "Protea" species exhibit both self-pollination and cross-pollination as a method of reproduction. Cross-pollination is preferred, though, as a method of reproduction because it provides genetic diversity in the population. When cultivating proteas, breeders use hand pollination as a controlled method to transfer pollen from one flower to another.


title: Protea

text: Proteas usually flower during spring. The general structure of their flower heads consists of a mass of flowers on a woody receptacle. The ovary is protected by the receptacle, thus is not seen when looking at the flower, but the anthers are present at the top of the flower, which can then easily transfer the pollen to the vectors. The common Proteaceae plants, e.g. "Protea", "Leucospermum", and "Leucadendron" are diploid organisms, thus they can freely hybridise with closely related species to form new cultivars. Unusually, not all the genera within the family Proteaceae are able to hybridise freely; for example, "Leucadendron" species cannot be crossed with "Leucospermum" species because of the difference in their haploid chromosome number (13 and 12, respectively). This genetic incompatibility results in pollinated flowers that yield either no fruit, or seedless fruit, as the resulting plant embryos, from the incompatible pollen and ovum, fail to develop.


title: Protea

text: Within the huge family Proteaceae, they are a member of the subfamily Proteoideae, which has Southern African and Australian members.


title: Protea

text: (listed by section: a 'section' has a name in two parts, consisting of the genus name and an epithet).


title: Texas School Book Depository

text: The Texas School Book Depository, now known as the Dallas County Administration Building, is a seven-floor building facing Dealey Plaza in Dallas, Texas. The building was Lee Harvey Oswald's vantage point during the assassination of United States President John F. Kennedy on November 22, 1963. The Warren Commission concluded that Oswald, an employee at the depository, shot and mortally wounded President Kennedy from a sixth floor window on the building's southeastern corner; Kennedy died at Parkland Memorial Hospital.


title: Texas School Book Depository

text: The building, located at 411 Elm Street on the northwest corner of Elm and North Houston Streets in downtown Dallas, is a Texas Historic Landmark.


title: Texas School Book Depository

text: The site of the building was originally owned by John Neely Bryan. During the 1880s, Maxime Guillot operated a wagon shop on the property. In 1894, the Rock Island Plow Company bought the land, and four years later constructed a five-story building for its Texas division, the Southern Rock Island Plow Company. In 1901, the building was hit by lightning and nearly burned to the ground. It was rebuilt in 1902 in the Commercial Romanesque Revival style and expanded to seven stories. In 1937, the Carraway Byrd Corporation purchased the property, but they defaulted on the loan. It was sold at public auction July 4, 1939 and purchased by D. Harold Byrd.


title: Texas School Book Depository

text: Under Byrd's ownership, the building remained empty until 1940, when it was leased by grocery wholesaler John Sexton & Co. Sexton Foods used this location as the branch office for sales, manufacturing, and distribution for the south and southwest United States. In November 1961, Sexton Foods moved to a modern distribution facility located at 650 Regal Row Dallas; by then, the building was known locally as the Sexton Building. The building was refurbished, and partitions, carpeting, air conditioning, and a new passenger elevator were added on the first four floors.


title: Texas School Book Depository

text: In 1963, the building was in use as a multi-floor warehouse storing school textbooks and other related materials and an order-fulfillment center by the privately owned Texas School Book Depository Company, which had moved from the first floor of the adjacent Dal-Tex Building. The company found that the upper floors had sustained oil damage from items stored there by the previous tenant, so they began to cover the floors with plywood to protect their books (stored in cardboard boxes) from the oil. Work had begun on the west side of the sixth floor just before President Kennedy's motorcade, "leaving the whole scene in disarray, with stock shifted as far as the east wall, and stacks in between piled unusually high." Lee Harvey Oswald was working as a temporary employee at the building, and fired three shots from a sixth floor window at the presidential motorcade on November 22, 1963.


title: Texas School Book Depository

text: The Texas School Book Depository Company maintained a second warehouse at 1917 Houston, several blocks north of the main building. The short four-story structure was well removed from the parade route, half-hidden on an unpaved section of Houston. Oswald's supervisor Roy Truly told the Warren Commission that he had the option to assign Oswald to either building on his first day at work. "Oswald and another fellow reported for work on the same day [October 15] and I needed one of them for the depository building. I picked Oswald." This second building was eventually destroyed to make way for the Woodall Rodgers Freeway.


title: Texas School Book Depository

text: During his two terms as mayor of Dallas, Wes Wise guided Dallas out from under the cloud of the assassination and at the same time saved the Texas School Book Depository from imminent destruction, preserving it for further research into the president's murder.


title: Texas School Book Depository

text: The Texas School Book Depository Company moved out in 1970 and the building was sold at auction to Aubrey Mayhew, a Nashville, Tennessee music producer and collector of Kennedy memorabilia, by the owner D. H. Byrd. In 1972, ownership reverted to Bard, and the building was purchased in 1977 by the government of Dallas County. After renovating the lower five floors of the building for use as county government offices, the Dallas County Administration Building was dedicated on March 29, 1981.


title: Texas School Book Depository

text: On President's Day 1989, the sixth floor opened to the public (for an admission charge) as the Sixth Floor Museum of assassination-related exhibits. On President's Day 2002, the seventh-floor gallery opened. The gallery opened on February 18, 2002 with the exhibit: "The Pulitzer Prize Photographs: Capture the Moment". A $2.5 million renovation turned the storage area on the seventh floor into a new gallery space for the museum. Other exhibits that have hung in the space include works of Andy Warhol.


title: Texas School Book Depository

text: On May 4, 2010, burglars attempted to steal a safe from the Sixth Floor Museum, but fled when "they were confronted by a security guard," leaving the unopened safe suspended from a winch on the back of a truck.


title: Mario Pašalić

text: Mario Pašalić (; born 9 February 1995) is a Croatian professional footballer who plays as a midfielder for side Atalanta and the Croatia national team.


title: Mario Pašalić

text: He began his career at Hajduk Split before moving to Chelsea for a reported £3 million in 2014. Chelsea loaned him to Elche, Monaco, Milan, Spartak Moscow and then Atalanta. Following two seasons at the Bergamasque club between 2018 and 2020, he was signed permanently ahead of the 2020–21 season.


title: Mario Pašalić

text: Pašalić made his senior international debut for Croatia in 2014, representing the side at UEFA Euro 2020 and the 2022 FIFA World Cup.


title: Mario Pašalić

text: Pašalić started playing football at county club NK GOŠK Kaštel Gomilica before joining the Hajduk Split's youth academy in 2006. A youth international, he first gained wider recognition in the 2011–12 season, scoring 17 goals for the under-17s, despite being a midfielder, and scoring the winner for the under-19s in a 3–2 success against Hrvatski Dragovoljac, which secured the club's championship trophy.


title: Mario Pašalić

text: During the pre-season, however, Pašalić was diagnosed with a staphylococcus infection, being sidelined for the first half of the 2012–13 campaign. He played his first match as a professional on 14 April 2013 replacing Ivan Vuković in the 90th minute of a 2–1 home success against Cibalia.


title: Mario Pašalić

text: In summer 2013, Pašalić signed a four-year professional contract with Hajduk and went on to make 36 appearances in all competitions during the 2013–14 season, scoring 11 goals and assisting a further five. On 14 September 2013, he scored two goals in a derby 2–0 victory against Dinamo Zagreb, and repeated the same fate on 8 February the following year, in a 2–1 win at city rivals RNK Split.


title: Mario Pašalić

text: On 9 July 2014, Chelsea announced the signing of Pašalić for an undisclosed fee. Upon signing, Pašalić said, "I am very happy because I am now a Chelsea player."


title: Mario Pašalić

text: On 22 July 2014, Pašalić joined Elche on a season-long loan deal. He made his La Liga debut on 25 August, starting and being booked in a 0–3 away loss against Barcelona. On 12 April 2015, Pašalić scored his first goal in the top flight of Spanish football, netting the last in a 2–0 win over Córdoba. On 29 April 2015, Pašalić scored in a 4–0 victory over Deportivo de La Coruña. On 3 May 2015, he scored a late goal which turned out to be the winner in the match against Málaga in a 2–1 victory.


title: Mario Pašalić

text: On 3 July 2015, it was announced that Pašalić will spend the 2015–16 season on loan at Monaco. Striker Radamel Falcao went on loan to Chelsea as part of the loan agreement for Pašalić to join the Monégasque side. During an interview about his loan move to Monaco, Pašalić stated that staying at Chelsea this season was never an option and that he "needs to improve, grow and then hope to get a chance with Chelsea".


title: Mario Pašalić

text: On 28 July, Pašalić made his Monaco debut in a 3–1 victory against Swiss side Young Boys in the UEFA Champions League third qualifying round, in which he scored the final goal to make it 3–1. On 8 August, Pašalić made his Ligue 1 debut after playing 25 minutes in a 2–1 win over Nice. On 19 August, Pašalić scored against Valencia, but it was not enough to stop Monaco from losing 3–1 in the first leg of the Champions League play-off. On 17 September, he made his Europa League debut in a 1–1 away draw with Anderlecht. In the 2015–16 Coupe de France, Pašalić scored twice in two appearances.


title: Mario Pašalić

text: On 27 August 2016, Pašalić joined Serie A side Milan on a season-long loan. A month after the loan was completed, there were reports that stated Milan was looking to cut the loan short and return Pašalić in January. He made his debut off the substitutes' bench on 30 October 2016 in a 1–0 win against Pescara. In the following game, Pašalić made his first start in a 2–1 win over Palermo. Pašalić scored his first goal for Milan in a 2–1 home victory against Crotone.


title: Mario Pašalić

text: Pašalić scored the winning penalty in the 2016 Supercoppa Italiana against Juventus, bringing Milan its first major trophy since 2011 after the regular match finished in a 1–1 draw (4–5 penalties). On 8 February 2017, Pašalić scored an 89th-minute winner against Bologna in Milan's 1–0 away win. On 2 April, Pašalić scored the equalizer in Milan's 1–1 away draw with Pescara.


title: Mario Pašalić

text: On 2 August 2017, Pašalić signed a new four-year deal with Chelsea and joined Russian champions Spartak Moscow on loan for the 2017–18 season.


title: Mario Pašalić

text: On 12 August, he scored his first goal for Spartak in a 2–1 away defeat to CSKA Moscow. He made his Champions League debut on 13 September in a 1–1 away draw with Maribor. On 27 November, he scored in a 3–1 home victory over Zenit Saint Petersburg. On 10 December, he once again scored in the Main Moscow derby, as Spartak won 3–0 at home.


title: Mario Pašalić

text: On 25 July 2018, Pašalić agreed to join Italian side Atalanta on a season-long loan with an option to purchase at the end of the spell. The Italian side finished the season as third in Serie A, qualifying for the next year's Champions League.


title: Mario Pašalić

text: On 4 July 2019, Pašalić signed a new contract at Chelsea until 2022 and returned to Atalanta on loan for a second season. On 18 September, Atalanta made their Champions League debut, as Dinamo Zagreb beat them 4–0 at Stadion Maksimir. On 6 November, Pašalić scored the equalizer against Manchester City in a 1–1 draw at San Siro. On 11 December, he scored the second goal in a 3–0 victory over Shakhtar Donetsk at Metalist Stadium. This made Atalanta the first debutant to reach the final 16 of the Champions League since Leicester City in 2016–17, and the first team ever to do it with only seven points. On 2 December 2019, Atalanta negotiated a €15 million option to buy to be activated at the end of the season. On 15 February 2020, he scored the winning goal in a 2–1 victory over Roma, only nineteen seconds after being substituted for Duván Zapata. On 19 February, he provided two assists for Josip Iličić and Hans Hateboer, as Atalanta defeated Valencia 4–1 and went on to reach the Champions League quarter-finals. On 22 June, Mario Pašalić joined Atalanta permanently for €15 million (£13.4 million). On 14 July, he scored his first career hat-trick in a 6–2 victory over Brescia, becoming the fifth Croatian to achieve that in Serie A. On 12 August, in a Champions League quarter-final against Paris Saint-Germain at Estádio da Luz, he scored the only goal for Atalanta before getting substituted off for Luis Muriel; however, PSG managed to overturn the result scoring two goals in injury time and knocking Atalanta out.


title: Mario Pašalić

text: In December 2020, Pašalić underwent a sports hernia surgery, which kept him off the pitch for more than two months. He returned to the pitch in a 3–1 defeat to Lazio, in which he scored Atalanta's only goal.


title: Mario Pašalić

text: On 14 May 2014, Pašalić was on Croatia manager Niko Kovač's 30-man list that was named to participate in the 2014 World Cup. He was not, however, selected for the final squad. He made his debut for Croatia on 4 September 2014 when he replaced Mario Mandžukić in a friendly home victory over Cyprus.


title: Mario Pašalić

text: In May 2018, he was named in Zlatko Dalić's preliminary 32-man squad for the 2018 FIFA World Cup in Russia but did not make the final 23.


title: Mario Pašalić

text: He scored his debut goal for the national team on 7 October 2020 in a friendly 2–1 victory over Switzerland.


title: Mario Pašalić

text: Pašalić was born in Mainz, Germany, but grew up in Kaštel Gomilica, Croatia. His father Ivan is a Bosnian Croat from Sarajlije near Tomislavgrad. His mother Slavica hails from Vrlika. He is a cousin of fellow footballer Ivan Krstanović.


title: Mario Pašalić

text: In June 2019, Pašalić married his longtime girlfriend Marija Grbeša on the island of Čiovo. In February 2022, Pašalić and Grbeša became parents of a baby boy, whom they named Luka.


title: John Spencer, 1st Earl Spencer

text: Spencer was born on 19 December 1734 at Althorp, his family's home in Northamptonshire. He was the only son of the Hon. John Spencer and his wife, the former Georgiana Caroline Carteret. His only sibling was his sister, Diana Spencer, who died at eight years old. After his father's alcohol-related death in 1746, his mother married secondly William Clavering-Cowper, 2nd Earl Cowper.


title: John Spencer, 1st Earl Spencer

text: His father was the youngest son of Charles Spencer, 3rd Earl of Sunderland, the First Lord of the Treasury and Lord President of the Council under George I, and his second wife, Lady Anne Churchill (third daughter of the 1st Duke of Marlborough), who served as Lady of the Bedchamber to Queen Anne. Among his paternal family were uncle Robert Spencer, 4th Earl of Sunderland, aunt Lady Anne Spencer (wife of 1st Viscount Bateman), Charles Spencer, 5th Earl of Sunderland (who succeeded his great-aunt, Henrietta, becoming the 3rd Duke of Marlborough), and aunt Lady Diana Spencer (wife of the 4th Duke of Bedford).


title: John Spencer, 1st Earl Spencer

text: His mother was the third daughter and heiress of Lord President of the Council John Carteret, 2nd Earl Granville, and his first wife, Frances Worsley (a daughter of Sir Robert Worsley, 4th Baronet). Among his maternal family were aunts Louisa Carteret (wife of the 2nd Viscount Weymouth), Grace Carteret (wife of the 4th Earl of Dysart), Frances Carteret (wife of the 4th Marquess of Tweeddale), and Sophia Carteret (wife of the 1st Marquess of Lansdowne).


title: John Spencer, 1st Earl Spencer

text: Spencer was the principal beneficiary under the will of his great-grandmother Sarah, Duchess of Marlborough who stipulated, however, that should he at any time accept "from any King or Queen of these realms any pension, or any office or employment, civil or military" (except the Rangership of Windsor Great or Little Park), the estate would pass to the next heir "as if the same John Spencer were actually dead."


title: John Spencer, 1st Earl Spencer

text: After going on a Grand Tour, Spencer returned to England where, in 1754, he was too young to stand for Parliament, but in return for James Grimston's election at St Albans, the Grimston family promised to support for him, or his nominee, on the next occasion. In March 1756 Spencer, standing on the Whig interest, but lost in the exceedingly expensive by-election at Bristol where Jarrit Smyth was elected. Nevertheless, Spencer was returned on 9 December for Warwick, mainly on the interest of Lord Brooke (later the 1st Earl of Warwick). Spencer represented Warwick alongside Henry Archer. On 27 November 1760, Spencer wrote to the Duke of Newcastle, the Prime Minister of Great Britain, stating:


title: John Spencer, 1st Earl Spencer

text: "As I am the representative of the Sunderland family, and as my particular circumstances are such (from the Duchess of Marlborough's will) that I cannot receive any favour from the King except a title, I should hope that if his Majesty thinks me worthy of a peerage he will not confer upon me a less dignity than that of a viscount... I hope your Grace has observed that ever since I sat in Parliament I have never failed in supporting the King and his ministers to the best of my ability."


title: John Spencer, 1st Earl Spencer

text: Newcastle replied that the King had received the application, but that there would be no immediate creations. Therefore, he continued canvassing St Albans but toward the end of February 1761, he nominated Viscount Nuneham in his place, likely after being informed of his impending creation. On 3 April 1761, he was created "Baron Spencer of Althorp" and "Viscount Spencer" by King George III.


title: John Spencer, 1st Earl Spencer

text: Spencer went into Opposition with Newcastle in 1762, and when the Rockingham Government was being formed, Newcastle noted in his lists: "Viscount Spencer to be created an earl" which happened when he was created "Viscount Althorp" and "Earl Spencer" on 1 November 1765. Next, he adhered to the Chatham Administration. Lord Spencer later served as High Steward of St Albans in 1772 and Mayor of St Albans in 1779.


title: John Spencer, 1st Earl Spencer

text: In 1754, the twenty year-old Spencer met seventeen year-old Margaret Georgiana Poyntz, who was the daughter of the English diplomat and courtier Stephen Poyntz. The two were instantly attracted to one another, but Spencer was uncertain if he would have his family's approval for the match and opted to spend several months travelling until his twenty-first birthday, when their approval would no longer be necessary. On his return they recognised their love had persisted, and shortly after his birthday they married in a secret ceremony on 20 December 1755 at Althorp, the Spencer family seat in Northamptonshire. The ceremony, held in an upper bedroom, occurred during a ball held in Spencer's honour with five hundred guests in attendance. They had five children, three of whom survived infancy:


title: John Spencer, 1st Earl Spencer

text: Spencer died aged 48, in 1783, near Bath. He had suffered from a long illness. He was buried in the family vault at St Mary's Church, Great Brington in Northamptonshire. His widow lived another thirty years before her death on 18 March 1814.


title: Salman Ali

text: Salman Ali is an Indian singer who won the 10th season of "Indian Idol". He was the first runner-up in the 2011 Sa Re Ga Ma Pa L'il Champs. In 2019, he made his debut as a playback singer with the song Jai Ho from the film Satellite Shankar. In 2019, he also sang the song Awara for the film "Dabangg 3". Salman sang the theme song for the Indian television series Chandragupta Maurya, which airs on Sony TV.


title: Salman Ali

text: Salman Ali was born in Punhana, a town in Haryana's Nuh district. Salman's family has made a living off of singing for the past four generations.


title: Oocyte cryopreservation

text: Human oocyte cryopreservation (egg freezing) is a procedure to preserve a woman's eggs (oocytes). This technique has been used to enable women to postpone pregnancy to a later date – whether for medical reasons (such as cancer treatment), or for social reasons (such as employment or studying). Several studies have shown that most infertility problems are due to germ cell deterioration related to aging. The intention of the procedure is that the woman may choose to have the eggs thawed, fertilized, and transferred to the uterus as embryos to facilitate a pregnancy in the future. The procedure's success rate (the chances of a live birth using frozen eggs) varies depending on the age of the woman, with odds being higher in younger, adult women.


title: Oocyte cryopreservation

text: Over 50,000 reproductive-age women are diagnosed with cancer each year in the United States. Chemotherapy and radiotherapy are toxic for oocytes, leaving few, if any, viable eggs. Egg-freezing offers women with cancer the chance to preserve their eggs, so that they can attempt to have children in the future.


title: Oocyte cryopreservation

text: Oocyte cryopreservation is an option for individuals undergoing IVF who object, either for religious or ethical reasons, to the practice of freezing embryos. In this way, there are no excess embryos created, and there need not be any disposal of unused frozen embryos.


title: Oocyte cryopreservation

text: Additionally, women with a family history of early menopause may have an interest in fertility preservation as to preserve viable eggs that could deteriorate at an earlier onset.


title: Oocyte cryopreservation

text: The egg retrieval process for oocyte cryopreservation is the same as that for in vitro fertilization. This includes one to several weeks of hormone injections that stimulate ovaries to ripen multiple eggs. When the eggs are mature, final maturation induction is performed, preferably by using a GnRH agonist rather than human chorionic gonadotrophin (hCG), since it decreases the risk of ovarian hyperstimulation syndrome with no evidence of a difference in live birth rate (in contrast to fresh cycles where usage of GnRH agonist has a lower live birth rate). The eggs are subsequently removed from the body by transvaginal oocyte retrieval. The procedure is usually conducted under sedation. The eggs are immediately frozen.


title: Oocyte cryopreservation

text: The egg is the largest cell in the human body and contains a large amount of water. When the egg is frozen, the ice crystals that form can destroy the integrity of the cell. To prevent this, the egg must be dehydrated prior to freezing. This is done using cryoprotectants which replace most of the water within the cell and inhibit the formation of ice crystals.


title: Oocyte cryopreservation

text: Eggs (oocytes) are frozen using either a controlled-rate, slow-cooling method or a newer flash-freezing process known as vitrification. Vitrification is much faster but requires higher concentrations of cryoprotectants to be added. The result of vitrification is a solid glass-like cell, free of ice crystals. Vitrification has been developed and successfully applied in IVF treatment with the first live birth following vitrification of oocytes achieved in 1999. Vitrification eliminates ice formation inside and outside of oocytes on cooling, during cryostorage and as the oocytes warm. Vitrification is associated with higher survival rates and enhanced development compared to slow-cooling when applied to oocytes in metaphase II (MII). Vitrification has also become the method of choice for pronuclear oocytes, although prospective randomized controlled trials are still lacking.


title: Oocyte cryopreservation

text: During the freezing process, the zona pellucida, or shell of the egg can be modified preventing fertilization. Thus, when eggs are thawed and pregnancy is desired, a fertilization procedure known as ICSI (Intracytoplasmic Sperm Injection) is performed by an embryologist whereby sperm is injected directly into the egg with a needle rather than allowing sperm to penetrate naturally by placing it around the egg in a dish.


title: Oocyte cryopreservation

text: Immature oocytes have been grown until maturation "in vitro", but it is not yet clinically available.


title: Oocyte cryopreservation

text: Early work investigating the percentage of transferred cycles showed lower frozen cycles compared with fresh cycles (approx. 30% and 50%), however more recent studies show "fertilization and pregnancy rates are similar to IVF/ICSI (or ("in vitro" fertilization/intracytoplasmic sperm injection) with fresh oocytes when [both when] vitrified and warmed oocytes are used as part of IVF/ICSI". These studies were completed mostly in young patients.


title: Oocyte cryopreservation

text: In a 2013 meta-analysis of more than 2,200 cycles using frozen eggs, scientists found the probability of having a live birth after three cycles was 31.5 percent for women who froze their eggs at age 25, 25.9 percent at age 30, 19.3 percent at age 35, and 14.8 percent at age 40.


title: Oocyte cryopreservation

text: Two 2000s studies showed that the rate of birth defects and chromosomal defects when using cryopreserved oocytes is consistent with that of natural conception.


title: Oocyte cryopreservation

text: Recent modifications in protocol regarding cryoprotectant composition, temperature and storage methods have had a large impact on the technology, and while it is still considered an experimental procedure, it is quickly becoming an option for women. Slow freezing traditionally has been the most commonly used method to cryopreserve oocytes, and is the method that has resulted in the most babies born from frozen oocytes worldwide. Ultra-rapid freezing or vitrification represents a potential alternative freezing method.


title: Oocyte cryopreservation

text: In the fall of 2009, The American Society for Reproductive Medicine (ASRM) issued an opinion on oocyte cryopreservation concluding that the science holds "great promise for applications in oocyte donation and fertility preservation" because recent laboratory modifications have resulted in improved oocyte survival, fertilization, and pregnancy rates from frozen-thawed oocytes in IVF. The ASRM noted that from the limited research performed to date, there does not appear to be an increase in chromosomal abnormalities, birth defects, or developmental deficits in the children born from cryopreserved oocytes. The ASRM recommended that, pending further research, oocyte cryopreservation should be introduced into clinical practice on an investigational basis and under the guidance of an Institutional Review Board (IRB). As with any new technology, safety and efficacy must be evaluated and demonstrated through continued research.


title: Oocyte cryopreservation

text: In October 2012, the ASRM lifted the experimental label from the technology for women with a medical need, citing success rates in live births, among other findings. However, they also warned against using it only to delay child-bearing.


title: Oocyte cryopreservation

text: In 2014, a Cochrane systematic review was published. It compared vitrification (the newest technology) versus slow freezing (the oldest one). Key results of that review showed that the clinical pregnancy rate was almost 4 times higher in the oocyte vitrification group than in the slow freezing group, with moderate quality of evidence.


title: Oocyte cryopreservation

text: Immature oocytes have been grown until maturation "in vitro" at a 10% survival rate, but no experiment has been performed to fertilize such oocytes.


title: Oocyte cryopreservation

text: The cost of the egg freezing procedure (without embryo transfer) in the United States, the United Kingdom and other European countries varies in between $5,000 and $12,000. This does not include the fertility medications involved in the procedure which can cost between $4,000 and $5,000. The cost of egg storage can vary from $100 to more than $1,000. Provisional health programs do not cover social egg freezing. Furthermore, no provinces provide funding for IVF after social egg freezing.


title: Oocyte cryopreservation

text: Medical tourism may have lower costs than performing egg freezing in high-cost countries like the US. Some well established medical tourism and IVF countries such as the Czech Republic, Ukraine and Cyprus offer egg freezing at competitive prices. It is a lower cost alternative to typical US options for egg freezing. Spain and the Czech Republic are popular destinations for this treatment.


title: Oocyte cryopreservation

text: Cryopreservation itself has always played a central role in assisted reproductive technology. With the first cryopreservation of sperm in 1953 and of embryos twenty five years later, these techniques have become routine. Dr. Christopher Chen of Singapore reported the world's first pregnancy in 1986 using previously frozen oocytes. This report stood alone for several years followed by studies reporting success rates using frozen eggs to be much lower than those of traditional in vitro fertilization (IVF) techniques using fresh oocytes. Providing the lead to a new direction in cryobiology, Dr. Lilia Kuleshova was the first scientist to achieve vitrification of human oocytes that resulted in a live birth in 1999. Articles published in the journal "Fertility and Sterility" reported that pregnancy rates using frozen oocytes that were comparable to those of cryopreserved embryos and even fresh embryos.


title: Oocyte cryopreservation

text: Elective oocyte cryopreservation, also known as social egg freezing, is non-essential egg freezing for the purpose of preserving fertility for delayed child-bearing when natural conception becomes more problematic. The frequency of this procedure has steadily increased since October 2012 when the American Society for Reproductive Medicine (ASRM) lifted the 'experimental' label from the process. There was a spike in interest in 2014 when global corporations Apple and Facebook revealed they were introducing egg freezing as a benefit for their female employees. This announcement was controversial as some women found it empowering and practical, while others viewed the message these companies were sending to women trying to have a successful long-term career and a family as harmful and alienating. A string of "egg freezing parties" hosted by third-party companies have also helped popularize the concept among young women.


title: Oocyte cryopreservation

text: Social science research suggests that women use elective egg freezing to disentangle their search for a romantic partner from their plans to have children.


title: Oocyte cryopreservation

text: In 2016, then US Secretary of Defense Ash Carter announced that the Department of Defense will cover the cost of freezing sperm or eggs through a pilot program for active duty service members, with the intention of preserving their ability to start a family even if they sustain certain combat injuries.


title: Oocyte cryopreservation

text: There are still warnings for women using this technology to fall pregnant at an older age as the risk of pregnancy complications increases with a mother's age. However, studies have shown that the risk of congenital abnormalities in babies born from frozen oocytes is not increased further when compared to naturally conceived babies.


title: Oocyte cryopreservation

text: The risks associated with egg freezing relate to the administration of medications to stimulate the ovaries and the procedure of egg collection.


title: Oocyte cryopreservation

text: The main risk associated with the administration of medications to stimulate the ovaries is ovarian hyper stimulation syndrome (OHSS). This is a transient syndrome in which there is increased permeability of the blood vessels, resulting in fluid loss from the vessels into the surrounding tissues. In most cases the syndrome is mild, with symptoms such as abdominal bloating, mild discomfort and nausea. In moderate OHSS there is increased abdominal bloating resulting in pain and vomiting. Reduced urine output may occur. Severe OHSS is serious with even further bloating so that the abdomen appears very distended, thirst and dehydration occur with minimal urine output. There may be shortness of breath and there is an increased risk of DVT and/or pulmonary embolism. Kidney and liver function can be compromised. Hospitalisation under specialist care is indicated. There is no treatment for OHSS, supportive care until the symptoms naturally resolve is required. If an hCG trigger has been used with no embryo transfer, OHSS usually resolves in 7–10 days. If an embryo transfer has occurred and pregnancy results, the symptoms may persist for several weeks. Doctors reduce the likelihood of OHSS occurring by decreasing the doses of gonadotropins (FSH) administered, using a GnRH agonist trigger (instead of an hCG trigger) and freezing all embryos for transfer rather than conducted a fresh embryo transfer.


title: Oocyte cryopreservation

text: Risks associated with the egg collection procedure relate to bleeding and infection. The collection procedure involves passing a needle through the wall of the vagina into vascular stimulated ovaries. A small amount of bleeding is inevitable. In rare cases, there is excessive bleeding into the abdomen requiring surgery. It is important that women undergoing the procedure advise their specialist of all medications, including herbal supplements, they are using so the specialist can assess whether any of these medications will affect the ability of the blood to clot. In relation to infection, provided the woman does not have additional risk factors for infection (suppressed immune system, use of immuno-suppressive medications or large ovarian endometriomas) the risk of infection is very low.


title: Oocyte cryopreservation

text: One additional risk of the ovaries being temporarily increased in size is ovarian torsion. Ovarian torsion occurs when an enlarged ovary twists around on itself, cutting off its blood supply. The condition is excruciatingly painful and requires urgent surgery to prevent the ischemic loss of the ovary.


title: Germ cell

text: A germ cell is any biological cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they undergo meiosis, followed by cellular differentiation into mature gametes, either eggs or sperm. Unlike animals, plants do not have germ cells designated in early development. Instead, germ cells can arise from somatic cells in the adult, such as the floral meristem of flowering plants.


title: Germ cell

text: Multicellular eukaryotes are made of two fundamental cell types: germ and somatic. Germ cells produce gametes and are the only cells that can undergo meiosis as well as mitosis. These cells are sometimes said to be immortal because they are the link between generations. Somatic cells are all the other cells that form the building blocks of the body and they only divide by mitosis. The lineage of germ cells is called the germline. Germ cell specification begins during cleavage in many animals or in the epiblast during gastrulation in birds and mammals. After transport, involving passive movements and active migration, germ cells arrive at the developing gonads. In humans, sexual differentiation starts approximately 6 weeks after conception. The end-products of the germ cell cycle are the egg or sperm.


title: Germ cell

text: Under special conditions "in vitro" germ cells can acquire properties similar to those of embryonic stem cells (ESCs). The underlying mechanism of that change is still unknown. These changed cells are then called embryonic germ cells. Both cell types are pluripotent in vitro, but only ESCs have proven pluripotency in vivo. Recent studies have demonstrated that it is possible to give rise to primordial germ cells from ESCs.


title: Germ cell

text: There are two mechanisms to establish the germ cell lineage in the embryo. The first way is called preformistic and involves that the cells destined to become germ cells inherit the specific germ cell determinants present in the germ plasm (specific area of the cytoplasm) of the egg (ovum). The unfertilized egg of most animals is asymmetrical: different regions of the cytoplasm contain different amounts of mRNA and proteins.


title: Germ cell

text: The second way is found in mammals, where germ cells are not specified by such determinants but by signals controlled by zygotic genes. In mammals, a few cells of the early embryo are induced by signals of neighboring cells to become primordial germ cells. Mammalian eggs are somewhat symmetrical and after the first divisions of the fertilized egg, the produced cells are all totipotent. This means that they can differentiate in any cell type in the body and thus germ cells. Specification of primordial germ cells in the laboratory mouse is initiated by high levels of bone morphogenetic protein (BMP) signaling, which activates expression of the transcription factors Blimp-1/Prdm1 and Prdm14.


title: Germ cell

text: It is speculated that induction was the ancestral mechanism, and that the preformistic, or inheritance, mechanism of germ cell establishment arose from convergent evolution. There are several key differences between these two mechanisms that may provide reasoning for the evolution of germ plasm inheritance. One difference is that typically inheritance occurs almost immediately during development (around the blastoderm stage) while induction typically does not occur until gastrulation. As germ cells are quiescent and therefore not dividing, they are not susceptible to mutation.


title: Germ cell

text: Since the germ cell lineage is not established right away by induction, there is a higher chance for mutation to occur before the cells are specified. Mutation rate data is available that indicates a higher rate of germ line mutations in mice and humans, species which undergo induction, than in C. elegans and Drosophila melanogaster, species which undergo inheritance. A lower mutation rate would be selected for, which is one possible reason for the convergent evolution of the germ plasm. However, more mutation rate data will need to be collected across several taxa, particularly data collected both before and after the specification of primordial germ cells before this hypothesis on the evolution of germ plasm can be backed by strong evidence.


title: Germ cell

text: Primordial germ cells, germ cells that still have to reach the gonads (also known as PGCs, precursor germ cells or gonocytes) divide repeatedly on their migratory route through the gut and into the developing gonads.


title: Germ cell

text: In the model organism "Drosophila", pole cells passively move from the posterior end of the embryo to the posterior midgut because of the infolding of the blastoderm. Then they actively move through the gut into the mesoderm. Endodermal cells differentiate and together with Wunen proteins they induce the migration through the gut. Wunen proteins are chemorepellents that lead the germ cells away from the endoderm and into the mesoderm. After splitting into two populations, the germ cells continue migrating laterally and in parallel until they reach the gonads. Columbus proteins, chemoattractants, stimulate the migration in the gonadal mesoderm.


title: Germ cell

text: In the acquatic frog "Xenopus" egg, the germ cell determinants are found in the most vegetal blastomeres. These presumptive PGCs are brought to the endoderm of the blastocoel by gastrulation. They are determined as germ cells when gastrulation is completed. Migration from the hindgut along the gut and across the dorsal mesentery then takes place. The germ cells split into two populations and move to the paired gonadal ridges. Migration starts with 3-4 cells that undergo three rounds of cell division so that about 30 PGCs arrive at the gonads. On the migratory path of the PGCs, the orientation of underlying cells and their secreted molecules such as fibronectin play an important role.


title: Germ cell

text: Mammals have a migratory path comparable to that in "Xenopus". Migration begins with 50 gonocytes and about 5,000 PGCs arrive at the gonads. Proliferation occurs also during migration and lasts for 3–4 weeks in humans.


title: Germ cell

text: PGCs come from the epiblast and migrate subsequently into the mesoderm, the endoderm and the posterior of the yolk sac. Migration then takes place from the hindgut along the gut and across the dorsal mesentery to reach the gonads (4.5 weeks in human beings). Fibronectin maps here also a polarized network together with other molecules. The somatic cells on the path of germ cells provide them attractive, repulsive, and survival signals. But germ cells also send signals to each other.


title: Germ cell

text: In reptiles and birds, germ cells use another path. PGCs come from the epiblast and move to the hypoblast to form the germinal crescent (anterior extraembryonic structure). The gonocytes then squeeze into blood vessels and use the circulatory system for transport. They squeeze out of the vessels when they are at height of the gonadal ridges. Cell adhesion on the endothelium of the blood vessels and molecules such as chemoattractants are probably involved in helping PGCs migrate.


title: Germ cell

text: The "SRY" (Sex-determining Region of the Y chromosome) directs male development in mammals by inducing the somatic cells of the gonadal ridge to develop into a testis, rather than an ovary. "Sry" is expressed in a small group of somatic cells of the gonads and influences these cells to become Sertoli cells (supporting cells in testis). Sertoli cells are responsible for sexual development along a male pathway in many ways. One of these ways involves stimulation of the arriving primordial cells to differentiate into sperm. In the absence of the "Sry" gene, primordial germ cells differentiate into eggs. Removing genital ridges before they start to develop into testes or ovaries results in the development of a female, independent of the carried sex chromosome.


title: Germ cell

text: Retinoic acid (RA) is an important factor that causes differentiation of primordial germ cells. In males, the mesonephros releases retinoic acid. RA then goes to the gonad causing an enzyme called CYP26B1 to be released by sertoli cells. CYP26B1 metabolizes RA, and because sertoli cells surround primordial germ cells (PGCs), PGCs never come into contact with RA, which results in a lack of proliferation of PGCs and no meiotic entry. This keeps spermatogenesis from starting too soon. In females, the mesonephros releases RA, which enters the gonad. RA stimulates Stra8, a critical gatekeeper of meiosis (1), and Rec8, causing primordial germ cells to enter meiosis. This causes the development of oocytes that arrest in meiosis I.


title: Germ cell

text: Gametogenesis, the development of diploid germ cells into either haploid eggs or sperm (respectively oogenesis and spermatogenesis) is different for each species but the general stages are similar. Oogenesis and spermatogenesis have many features in common, they both involve:


title: Germ cell

text: After migration primordial germ cells will become oogonia in the forming gonad (ovary). The oogonia proliferate extensively by mitotic divisions, up to 5-7 million cells in humans. But then many of these oogonia die and about 50,000 remain. These cells differentiate into primary oocytes. In week 11-12 "post coitus" the first meiotic division begins (before birth for most mammals) and remains arrested in prophase I from a few days to many years depending on the species. It is in this period or in some cases at the beginning of sexual maturity that the primary oocytes secrete proteins to form a coat called zona pellucida and they also produce cortical granules containing enzymes and proteins needed for fertilization. Meiosis stands by because of the follicular granulosa cells that send inhibitory signals through gap junctions and the zona pellucida. Sexual maturation is the beginning of periodic ovulation. Ovulation is the regular release of one oocyte from the ovary into the reproductive tract and is preceded by follicular growth. A few follicle cells are stimulated to grow but only one oocyte is ovulated. A primordial follicle consists of an epithelial layer of follicular granulosa cells enclosing an oocyte. The pituitary gland secrete follicle-stimulating hormones (FSHs) that stimulate follicular growth and oocyte maturation. The thecal cells around each follicle secrete estrogen. This hormone stimulates the production of FSH receptors on the follicular granulosa cells and has at the same time a negative feedback on FSH secretion. This results in a competition between the follicles and only the follicle with the most FSH receptors survives and is ovulated. Meiotic division I goes on in the ovulated oocyte stimulated by luteinizing hormones (LHs) produced by the pituitary gland. FSH and LH block the gap junctions between follicle cells and the oocyte therefore inhibiting communication between them. Most follicular granulosa cells stay around the oocyte and so form the cumulus layer. Large non-mammalian oocytes accumulate egg yolk, glycogen, lipids, ribosomes, and the mRNA needed for protein synthesis during early embryonic growth. These intensive RNA biosynthese are mirrored in the structure of the chromosomes, which decondense and form lateral loops giving them a lampbrush appearance (see Lampbrush chromosome). Oocyte maturation is the following phase of oocyte development. It occurs at sexual maturity when hormones stimulate the oocyte to complete meiotic division I. The meiotic division I produces 2 cells differing in size: a small polar body and a large secondary oocyte. The secondary oocyte undergoes meiotic division II and that results in the formation of a second small polar body and a large mature egg, both being haploid cells. The polar bodies degenerate. Oocyte maturation stands by at metaphase II in most vertebrates. During ovulation, the arrested secondary oocyte leaves the ovary and matures rapidly into an egg ready for fertilization. Fertilization will cause the egg to complete meiosis II. In human females there is proliferation of the oogonia in the fetus, meiosis starts then before birth and stands by at meiotic division I up to 50 years, ovulation begins at puberty.


title: Germ cell

text: A 10 - 20 μm large somatic cell generally needs 24 hours to double its mass for mitosis. By this way it would take a very long time for that cell to reach the size of a mammalian egg with a diameter of 100 μm (some insects have eggs of about 1,000 μm or greater). Eggs have therefore special mechanisms to grow to their large size. One of these mechanisms is to have extra copies of genes: meiotic division I is paused so that the oocyte grows while it contains two diploid chromosome sets. Some species produce many extra copies of genes, such as amphibians, which may have up to 1 or 2 million copies. A complementary mechanism is partly dependent on syntheses of other cells. In amphibians, birds, and insects, yolk is made by the liver (or its equivalent) and secreted into the blood. Neighboring accessory cells in the ovary can also provide nutritive help of two types. In some invertebrates some oogonia become nurse cells. These cells are connected by cytoplasmic bridges with oocytes. The nurse cells of insects provide oocytes macromolecules such as proteins and mRNA. Follicular granulosa cells are the second type of accessory cells in the ovary in both invertebrates and vertebrates. They form a layer around the oocyte and nourish them with small molecules, no macromolecules, but eventually their smaller precursor molecules, by gap junctions.


title: Germ cell

text: The mutation frequency of female germline cells in mice is about 5-fold lower than that of somatic cells, according to one study.


title: Germ cell

text: The mouse oocyte in the dictyate (prolonged diplotene) stage of meiosis actively repairs DNA damage, whereas DNA repair was not detected in the pre-dictyate (leptotene, zygotene and pachytene) stages of meiosis. The long period of meiotic arrest at the four chromatid dictyate stage of meiosis may facilitate recombinational repair of DNA damages.


title: Germ cell

text: Mammalian spermatogenesis is representative for most animals. In human males, spermatogenesis begins at puberty in seminiferous tubules in the testicles and go on continuously. Spermatogonia are immature germ cells. They proliferate continuously by mitotic divisions around the outer edge of the seminiferous tubules, next to the basal lamina. Some of these cells stop proliferation and differentiate into primary spermatocytes. After they proceed through the first meiotic division, two secondary spermatocytes are produced. The two secondary spermatocytes undergo the second meiotic division to form four haploid spermatids. These spermatids differentiate morphologically into sperm by nuclear condensation, ejection of the cytoplasm and formation of the acrosome and flagellum.


title: Germ cell

text: The developing male germ cells do not complete cytokinesis during spermatogenesis. Consequently, cytoplasmic bridges exist during interphase to ensure connection between the clones of differentiating daughter cells. These bridges are called a syncytium, and feature a TEX14 and KIF23 ring in their centre. In this way the haploid cells are supplied with all the products of a complete diploid genome. Sperm that carry a Y chromosome, for example, are supplied with essential molecules that are encoded by genes on the X chromosome.


title: Germ cell

text: Success of germ cell proliferation and differentiation is also ensured by a balance between germ cell development and programmed cell death. Identification of «death triggering signals» and corresponding receptor proteins is important for the fertilization potential of males. Apoptosis in germ cells can be induced by variety of naturally occurring toxicant. Receptors belonging to the taste 2 family are specialized to detect bitter compounds including extremely toxic alkaloids. So taste receptors play a functional role for controlling apoptosis in male reproductive tissue.


title: Germ cell

text: The mutation frequencies for cells throughout the different stages of spermatogenesis in mice is similar to that in female germline cells, that is 5 to 10-fold lower than the mutation frequency in somatic cells Thus low mutation frequency is a feature of germline cells in both sexes.


title: Germ cell

text: Homologous recombinational repair of double-strand breaks occurs in mouse during sequential stages of spermatogenesis, but is most prominent in spermatocytes. The lower frequencies of mutation in germ cells compared to somatic cells appears to be due to more efficient removal of DNA damages by repair processes including homologous recombination repair during meiosis. Mutation frequency during spermatogenesis increases with age. The mutations in spermatogenic cells of old mice include an increased prevalence of transversion mutations compared to young and middle-aged mice.


title: Germ cell

text: Germ cell tumor is a rare cancer that can affect people at all ages. As of 2018, germ cell tumors account for 3% of all cancers in children and adolescents 0–19 years old.


title: Germ cell

text: Germ cell tumors are generally located in the gonads but can also appear in the abdomen, pelvis, mediastinum, or brain. Germ cells migrating to the gonads may not reach that intended destination and a tumor can grow wherever they end up, but the exact cause is still unknown. These tumors can be benign or malignant.


title: Germ cell

text: On arrival at the gonad, primordial germ cells that do not properly differentiate may produce germ cell tumors of the ovary or testis in a mouse model.


title: Germ cell

text: Inducing differentiation of certain cells to germ cells has many applications. One implication of induced differentiation is that it may allow for the eradication of male and female factor infertility. Furthermore, it would allow same-sex couples to have biological children if sperm could be produced from female cells or if eggs could be produced from male cells. Efforts to create sperm and eggs from skin and embryonic stem cells were pioneered by Hayashi and Saitou's research group at Kyoto University. These researchers produced primordial germ cell-like cells (PGLCs) from embryonic stem cells (ESCs) and skin cells in vitro.


title: Germ cell

text: Hayashi and Saitou's group was able to promote the differentiation of embryonic stem cells into PGCs with the use of precise timing and bone morphogenetic protein 4 (Bmp4). Upon succeeding with embryonic stem cells, the group was able to successfully promote the differentiation of induced pluripotent stem cells (iPSCs) into PGLCs. These primordial germ cell-like cells were then used to create spermatozoa and oocytes.


title: Germ cell

text: Efforts for human cells are less advanced due to the fact that the PGCs formed by these experiments are not always viable. In fact Hayashi and Saitou's method is only one third as effective as current in vitro fertilization methods, and the produced PGCs are not always functional. Furthermore, not only are the induced PGCs not as effective as naturally occurring PGCs, but they are also less effective at erasing their epigenetic markers when they differentiate from iPSCs or ESCs to PGCs.


title: Germ cell

text: There are also other applications of induced differentiation of germ cells. Another study showed that culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells, as evidenced by gene expression analysis.


title: Bruce Buck

text: Bruce Mackie Buck (born March 1946) is an American lawyer and founding managing partner of the London office of law firm Skadden, Arps, Slate, Meagher & Flom. He was also the Chairman of Chelsea Football Club. His practice areas are European mergers and acquisitions, project finance and capital markets.


title: Bruce Buck

text: Bruce Buck has been practising law in Europe since 1983. He left New York for England in 1983 for a “standard tour of duty” of two or three years with his previous law firm White & Case. Five years later he was headhunted by M&A specialists Skadden Arps to develop the firm's European practice from scratch and has stayed on ever since.


title: Bruce Buck

text: As the partner in charge of Skadden's European offices, his work includes a broad range of transactions in the capital markets area. Buck represents both European and non-European clients in a full range of crossborder financing transactions, generally in connection with equity offerings or high-yield and other debt financings.


title: Bruce Buck

text: Buck's involvement with Chelsea began through his position as European head of the American law firm Skadden, Arps, Slate, Meagher & Flom. Skadden Arps specialises in mergers, acquisitions and capital market transactions, and Buck had personally done legal work on a number of acquisitions for the Russian company Siberian Oil (Sibneft), through which he came to advise Russian-Israeli billionaire Roman Abramovich, formerly the majority shareholder in Sibneft.


title: Bruce Buck

text: The £140 million acquisition of all of the outstanding shares of the London Stock Exchange-listed company Chelsea Village plc was his first experience of taking over a football club.


title: Bruce Buck

text: Buck remained in his role, despite the ownership change at Chelsea in May 2022. However this changed on 20 June 2022, when the club announced that he would be stepping down from his role effective 30 June. Though he would continue to work for the club as a Senior Advisor. the chairman role has been replaced by club co-owner Todd Boehly.


title: Algebraic topology

text: Algebraic topology is a branch of mathematics that uses tools from abstract algebra to study topological spaces. The basic goal is to find algebraic invariants that classify topological spaces up to homeomorphism, though usually most classify up to homotopy equivalence.


title: Algebraic topology

text: Although algebraic topology primarily uses algebra to study topological problems, using topology to solve algebraic problems is sometimes also possible. Algebraic topology, for example, allows for a convenient proof that any subgroup of a free group is again a free group.


title: Algebraic topology

text: In mathematics, homotopy groups are used in algebraic topology to classify topological spaces. The first and simplest homotopy group is the fundamental group, which records information about loops in a space. Intuitively, homotopy groups record information about the basic shape, or holes, of a topological space.


title: Algebraic topology

text: In algebraic topology and abstract algebra, homology (in part from Greek ὁμός "homos" "identical") is a certain general procedure to associate a sequence of abelian groups or modules with a given mathematical object such as a topological space or a group.


title: Algebraic topology

text: In homology theory and algebraic topology, cohomology is a general term for a sequence of abelian groups defined from a cochain complex. That is, cohomology is defined as the abstract study of cochains, cocycles, and coboundaries. Cohomology can be viewed as a method of assigning algebraic invariants to a topological space that has a more refined algebraic structure than does homology. Cohomology arises from the algebraic dualization of the construction of homology. In less abstract language, cochains in the fundamental sense should assign 'quantities' to the "chains" of homology theory.


title: Algebraic topology

text: A manifold is a topological space that near each point resembles Euclidean space. Examples include the plane, the sphere, and the torus, which can all be realized in three dimensions, but also the Klein bottle and real projective plane which cannot be embedded in three dimensions, but can be embedded in four dimensions. Typically, results in algebraic topology focus on global, non-differentiable aspects of manifolds; for example Poincaré duality.


title: Algebraic topology

text: Knot theory is the study of mathematical knots. While inspired by knots that appear in daily life in shoelaces and rope, a mathematician's knot differs in that the ends are joined so that it cannot be undone. In precise mathematical language, a knot is an embedding of a circle in 3-dimensional Euclidean space, formula_1. Two mathematical knots are equivalent if one can be transformed into the other via a deformation of formula_1 upon itself (known as an ambient isotopy); these transformations correspond to manipulations of a knotted string that do not involve cutting the string or passing the string through itself.


title: Algebraic topology

text: A simplicial complex is a topological space of a certain kind, constructed by "gluing together" points, line segments, triangles, and their "n"-dimensional counterparts (see illustration). Simplicial complexes should not be confused with the more abstract notion of a simplicial set appearing in modern simplicial homotopy theory. The purely combinatorial counterpart to a simplicial complex is an abstract simplicial complex.


title: Algebraic topology

text: A CW complex is a type of topological space introduced by J. H. C. Whitehead to meet the needs of homotopy theory. This class of spaces is broader and has some better categorical properties than simplicial complexes, but still retains a combinatorial nature that allows for computation (often with a much smaller complex).


title: Algebraic topology

text: An older name for the subject was combinatorial topology, implying an emphasis on how a space X was constructed from simpler ones (the modern standard tool for such construction is the CW complex). In the 1920s and 1930s, there was growing emphasis on investigating topological spaces by finding correspondences from them to algebraic groups, which led to the change of name to algebraic topology. The combinatorial topology name is still sometimes used to emphasize an algorithmic approach based on decomposition of spaces.


title: Algebraic topology

text: In the algebraic approach, one finds a correspondence between spaces and groups that respects the relation of homeomorphism (or more general homotopy) of spaces. This allows one to recast statements about topological spaces into statements about groups, which have a great deal of manageable structure, often making these statement easier to prove.


title: Algebraic topology

text: Two major ways in which this can be done are through fundamental groups, or more generally homotopy theory, and through homology and cohomology groups. The fundamental groups give us basic information about the structure of a topological space, but they are often nonabelian and can be difficult to work with. The fundamental group of a (finite) simplicial complex does have a finite presentation.


title: Algebraic topology

text: Homology and cohomology groups, on the other hand, are abelian and in many important cases finitely generated. Finitely generated abelian groups are completely classified and are particularly easy to work with.


title: Algebraic topology

text: In general, all constructions of algebraic topology are functorial; the notions of category, functor and natural transformation originated here. Fundamental groups and homology and cohomology groups are not only "invariants" of the underlying topological space, in the sense that two topological spaces which are homeomorphic have the same associated groups, but their associated morphisms also correspond—a continuous mapping of spaces induces a group homomorphism on the associated groups, and these homomorphisms can be used to show non-existence (or, much more deeply, existence) of mappings.


title: Algebraic topology

text: One of the first mathematicians to work with different types of cohomology was Georges de Rham. One can use the differential structure of smooth manifolds via de Rham cohomology, or Čech or sheaf cohomology to investigate the solvability of differential equations defined on the manifold in question. De Rham showed that all of these approaches were interrelated and that, for a closed, oriented manifold, the Betti numbers derived through simplicial homology were the same Betti numbers as those derived through de Rham cohomology. This was extended in the 1950s, when Samuel Eilenberg and Norman Steenrod generalized this approach. They defined homology and cohomology as functors equipped with natural transformations subject to certain axioms (e.g., a weak equivalence of spaces passes to an isomorphism of homology groups), verified that all existing (co)homology theories satisfied these axioms, and then proved that such an axiomatization uniquely characterized the theory.


title: 61*

text: 61* is a 2001 American made-for-television sports drama film written by Hank Steinberg and directed by Billy Crystal. It stars Barry Pepper as Roger Maris and Thomas Jane as Mickey Mantle on their quest to break Babe Ruth's 1927 single-season home run record of 60 during the 1961 season of the New York Yankees. The film first aired on HBO on April 28, 2001.


title: 61*

text: In 1998, the family of the late Roger Maris goes to Busch Stadium to witness Mark McGwire of the St. Louis Cardinals break their father's record with a 62nd home run. Maris' widow, Pat, is hospitalized due to complications from arrhythmia and watches the game on television from a hospital bed.


title: 61*

text: Decades earlier in 1961, Maris is presented with the Most Valuable Player award for the 1960 baseball season, but Mickey Mantle remains the New York Yankees' superstar. Mantle starts off hot while Maris struggles. Maris suspects he may be traded, but new manager Ralph Houk has Mantle and Maris switch places in the Yankees' batting order to see if it helps. It does, and Maris begins to hit home runs at a record pace. Mantle keeps pace and it becomes clear that both "M&M Boys" will make a run at Babe Ruth's record of 60 homers in one season.


title: 61*

text: Mickey's life off the field is taking a toll on his playing. He drinks, enjoys the Manhattan nightlife and arrives at the ballpark hung over. More than once, pitcher Whitey Ford has to bail him out or sober him up. To keep Mantle out of trouble, Maris and teammate/roommate Bob Cerv invite him to move in with them in a modest home in Queens, with one condition: no women.


title: 61*

text: New York's fans and media pull for the popular and personable Mantle, a long-time Yankee. The quieter Maris is viewed as an outsider, aloof and unworthy. As the two men close in on the record, MLB Commissioner Ford Frick, who was Babe Ruth's ghostwriter, makes a decision: unless the record is broken in 154 games, as Ruth did in 1927, the new mark would be listed separately indicating it had been done in baseball's newly expanded 162-game season.


title: 61*

text: It appears Mantle is not going to make it; his health deteriorates and he plays in constant pain. Maris, meanwhile, is unaccustomed to such a high level of public scrutiny and is uncomfortable interacting with the media, who dissect and distort everything he says or does. The fans heckle Maris and even throw objects at him on the field. Soon he begins receiving hate mail and death threats. His wife lives far from New York, usually available only by phone. The stress becomes so intense that Maris' hair begins to fall out in clumps. The Yankees owner also tries to favor Mantle by asking Houk to switch Mantle and Maris in the batting order, but Houk refuses, because the redesigned lineup has been winning a higher percentage of games.


title: 61*

text: Chronic injury and alcohol abuse catch up with Mantle, and an ill-advised injection by a doctor infects his hip and lands him in a hospital bed. With Mantle gone from the lineup, the stage becomes set for Maris. He fails to break the record in the 154th game of the season, but he does finally hit his 61st home run during the final game of the season.


title: 61*

text: Most of the baseball action scenes, including those set at Yankee Stadium, were actually filmed at Tiger Stadium in Detroit, Michigan. A combination of strategic photographing and post-production effects were used to enhance the illusion of the "classic" layout of Yankee Stadium. Tiger Stadium was credited as "playing" Yankee Stadium in the closing credits. Tiger Stadium also "played itself" as the home of the Tigers when the Yankees played them in Detroit.


title: 61*

text: The shots depicting Fenway Park and Baltimore's Memorial Stadium were shot at the Los Angeles Memorial Coliseum.


title: 61*

text: Review aggregator Rotten Tomatoes reports that 86% out of 28 professional critics gave the film a positive review, with an average rating of 6.8/10.


title: 61*

text: Film critic Richard Roeper named "61*" one of his top five all-time favorite baseball movies. In 2002, actor Barry Pepper was a Golden Globe nominee for Best Performance by an Actor in a Miniseries or a Motion Picture Made for Television.


title: 61*

text: In the beginning of the film, Bob Cerv was seen with the Yankees on Opening Day. In reality, Cerv was a member of the Los Angeles Angels until May and then was traded to the Yankees.


title: 61*

text: Also on opening day, the broadcast announcer refers to the opposing Minnesota Twins pitcher as Camilo Pascual. In fact, the Twins' pitcher that day was Pedro Ramos, who would later distinguish himself as a reliever for the Yankees. As the Twins are warming up, two players, wearing numbers 2 (Zoilo Versalles) and 7 (Lenny Green) are seen. In the film, number 7 for the Twins throws right-handed and appears to be Caucasian. In fact, Green, who started in center field opening day for the Twins, is an African-American who batted and threw left-handed.


title: 61*

text: In his 2013 memoir, "Still Foolin' 'Em", Billy Crystal recounts how before it aired on HBO, the film was shown at the White House for a small audience that included President George W. Bush, who once owned baseball's Texas Rangers. A home run in the film, depicted as being hit off pitcher Frank Lary, was actually hit off left-hander Hank Aguirre, which the president pointed out to Crystal. Lary gave up Maris' 52nd and 57th homers of that 1961 season, but the one in question (his 53rd) did indeed come against Aguirre.


title: 61*

text: The film depicts the Yankees 154th game of the season, facing the Baltimore Orioles. Oriole's pitcher Hoyt Wilhelm is brought in to relieve in the 9th inning with 2 outs to face Maris. Maris had homered earlier in the game for number 59, and if he homered again he would tie Babe Ruth's record of 60 home runs in 154 games. This would give Maris outright share with Ruth of the home run record, voiding commissioner Ford Frick's ruling earlier in July that if Maris did not break Ruth's record by game 154, the records would be separated due to Maris's season being 8 games longer than Ruth's.


title: 61*

text: The film shows Yankee players in the dugout in disgust at the Orioles bringing their top reliever solely to face Maris, as Wilhelm's effective knuckleball would make it more difficult for Maris to homer off on a windy night. In reality, Wilhelm was brought in at the top of the inning, and had already gotten two Yankees out before facing and getting out Maris. When Wilhelm was brought in, the film shows the Orioles manager threatening to fine him $5,000 if he threw Maris a fastball, a story which has never been confirmed.


title: Rate equation

text: In chemistry, the rate law or rate equation for a reaction is an equation that links the initial or forward reaction rate with the concentrations or pressures of the reactants and constant parameters (normally rate coefficients and partial reaction orders). For many reactions, the initial rate is given by a power law such as


title: Rate equation

text: where and express the concentration of the species and usually in moles per liter (molarity, ). The exponents and are the partial "orders of reaction" for and and the "overall" reaction order is the sum of the exponents. These are often positive integers, but they may also be zero, fractional, or negative. The constant is the reaction rate constant or "rate coefficient" of the reaction. Its value may depend on conditions such as temperature, ionic strength, surface area of an adsorbent, or light irradiation. If the reaction goes to completion, the rate equation for the reaction rate formula_2 applies throughout the course of the reaction.


title: Rate equation

text: Elementary (single-step) reactions and reaction steps have reaction orders equal to the stoichiometric coefficients for each reactant. The overall reaction order, i.e. the sum of stoichiometric coefficients of reactants, is always equal to the molecularity of the elementary reaction. However, complex (multi-step) reactions may or may not have reaction orders equal to their stoichiometric coefficients. This implies that the order and the rate equation of a given reaction cannot be reliably deduced from the stoichiometry and must be determined experimentally, since an unknown reaction mechanism could be either elementary or complex. When the experimental rate equation has been determined, it is often of use for deduction of the reaction mechanism.


title: Rate equation

text: The rate equation of a reaction with an assumed multi-step mechanism can often be derived theoretically using quasi-steady state assumptions from the underlying elementary reactions, and compared with the experimental rate equation as a test of the assumed mechanism. The equation may involve a fractional order, and may depend on the concentration of an intermediate species.


title: Rate equation

text: A reaction can also have an "undefined" reaction order with respect to a reactant if the rate is not simply proportional to some power of the concentration of that reactant; for example, one cannot talk about reaction order in the rate equation for a bimolecular reaction between adsorbed molecules:


title: Rate equation

text: The prefactors −1, −2 and 3 (with negative signs for reactants because they are consumed) are known as stoichiometric coefficients. One molecule of A combines with two of B to form 3 of C, so if we use the symbol [X] for the number of moles of chemical X,


title: Rate equation

text: If the reaction takes place in a closed system at constant temperature and volume, without a build-up of reaction intermediates, the "reaction rate" formula_7 is defined as


title: Rate equation

text: The initial reaction rate formula_9 has some functional dependence on the concentrations of the reactants,


title: Rate equation

text: and this dependence is known as the "rate equation" or "rate law". This law generally cannot be deduced from the chemical equation and must be determined by experiment.


title: Rate equation

text: The constant is called the "rate constant". The exponents, which can be fractional, are called "partial orders of reaction" and their sum is the overall order of reaction.


title: Rate equation

text: In a dilute solution, an elementary reaction (one having a single step with a single transition state) is empirically found to obey the law of mass action. This predicts that the rate depends only on the concentrations of the reactants, raised to the powers of their stoichiometric coefficients.


title: Rate equation

text: This can be used to estimate the order of reaction of each reactant. For example, the initial rate can be measured in a series of experiments at different initial concentrations of reactant with all other concentrations kept constant, so that


title: Rate equation

text: The slope of a graph of as a function of formula_14 then corresponds to the order with respect to reactant .


title: Rate equation

text: The tentative rate equation determined by the method of initial rates is therefore normally verified by comparing the concentrations measured over a longer time (several half-lives) with the integrated form of the rate equation; this assumes that the reaction goes to completion.


title: Rate equation

text: where is the concentration at time and is the initial concentration at zero time. The first-order rate law is confirmed if formula_16 is in fact a linear function of time. In this case the rate constant is equal to the slope with sign reversed.


title: Rate equation

text: The partial order with respect to a given reactant can be evaluated by the method of flooding (or of isolation) of Ostwald. In this method, the concentration of one reactant is measured with all other reactants in large excess so that their concentration remains essentially constant. For a reaction with rate law formula_17 the partial order with respect to is determined using a large excess of . In this case


title: Rate equation

text: and may be determined by the integral method. The order with respect to under the same conditions (with in excess) is determined by a series of similar experiments with a range of initial concentration so that the variation of can be measured.


title: Rate equation

text: For zero-order reactions, the reaction rate is independent of the concentration of a reactant, so that changing its concentration has no effect on the rate of the reaction. Thus, the concentration changes linearly with time. This may occur when there is a bottleneck which limits the number of reactant molecules that can react at the same time, for example if the reaction requires contact with an enzyme or a catalytic surface.


title: Rate equation

text: Many enzyme-catalyzed reactions are zero order, provided that the reactant concentration is much greater than the enzyme concentration which controls the rate, so that the enzyme is "saturated". For example, the biological oxidation of ethanol to acetaldehyde by the enzyme liver alcohol dehydrogenase (LADH) is zero order in ethanol.


title: Rate equation

text: Similarly reactions with heterogeneous catalysis can be zero order if the catalytic surface is saturated. For example, the decomposition of phosphine () on a hot tungsten surface at high pressure is zero order in phosphine, which decomposes at a constant rate.


title: Rate equation

text: In homogeneous catalysis zero order behavior can come about from reversible inhibition. For example, ring-opening metathesis polymerization using third-generation Grubbs catalyst exhibits zero order behavior in catalyst due to the reversible inhibition that occurs between pyridine and the ruthenium center.


title: Rate equation

text: A "first order reaction" depends on the concentration of only one reactant (a "unimolecular reaction"). Other reactants can be present, but their concentration has no effect on the rate. The rate law for a first order reaction is


title: Rate equation

text: Although not affecting the above math, the majority of first order reactions proceed via intermolecular collisions. Such collisions, which contribute the energy to the reactant, are necessarily second order. The rate of these collisions is, however, masked by the fact that the rate determining step remains the unimolecular breakdown of the energized reactant.


title: Rate equation

text: In organic chemistry, the class of S1 (nucleophilic substitution unimolecular) reactions consists of first-order reactions. For example, in the reaction of aryldiazonium ions with nucleophiles in aqueous solution, , the rate equation is formula_22 where Ar indicates an aryl group.


title: Rate equation

text: A reaction is said to be second order when the overall order is two. The rate of a second-order reaction may be proportional to one concentration squared, formula_23 or (more commonly) to the product of two concentrations, formula_24 As an example of the first type, the reaction is second-order in the reactant and zero order in the reactant CO. The observed rate is given by formula_25 and is independent of the concentration of CO.


title: Rate equation

text: For the rate proportional to a single concentration squared, the time dependence of the concentration is given by


title: Rate equation

text: The second type includes nucleophilic addition-elimination reactions, such as the alkaline hydrolysis of ethyl acetate:


title: Rate equation

text: The rate is first-order in one reactant (ethyl acetate), and also first-order in imidazole, which as a catalyst does not appear in the overall chemical equation.


title: Rate equation

text: Another well-known class of second-order reactions are the S2 (bimolecular nucleophilic substitution) reactions, such as the reaction of n-butyl bromide with sodium iodide in acetone:


title: Rate equation

text: This same compound can be made to undergo a bimolecular (E2) elimination reaction, another common type of second-order reaction, if the sodium iodide and acetone are replaced with sodium tert-butoxide as the salt and tert-butanol as the solvent:


title: Rate equation

text: If the concentration of a reactant remains constant (because it is a catalyst, or because it is in great excess with respect to the other reactants), its concentration can be included in the rate constant, leading to a "pseudo–first-order" (or occasionally pseudo–second-order) rate equation. For a typical second-order reaction with rate equation formula_30 if the concentration of reactant B is constant then formula_31 where the pseudo–first-order rate constant formula_32 The second-order rate equation has been reduced to a pseudo–first-order rate equation, which makes the treatment to obtain an integrated rate equation much easier.


title: Rate equation

text: One way to obtain a pseudo-first order reaction is to use a large excess of one reactant (say, [B]≫[A]) so that, as the reaction progresses, only a small fraction of the reactant in excess (B) is consumed, and its concentration can be considered to stay constant. For example, the hydrolysis of esters by dilute mineral acids follows pseudo-first order kinetics, where the concentration of water is constant because it is present in large excess:


title: Rate equation

text: The hydrolysis of sucrose () in acid solution is often cited as a first-order reaction with rate formula_33 The true rate equation is third-order, formula_34 however, the concentrations of both the catalyst and the solvent are normally constant, so that the reaction is pseudo–first-order.


title: Rate equation

text: Elementary reaction steps with order 3 (called "ternary reactions") are rare and unlikely to occur. However, overall reactions composed of several elementary steps can, of course, be of any (including non-integer) order.


title: Rate equation

text: Here stands for concentration in molarity (mol · L), for time, and for the reaction rate constant. The half-life of a first order reaction is often expressed as "t" = 0.693/"k" (as ln(2)≈0.693).


title: Rate equation

text: In fractional order reactions, the order is a non-integer, which often indicates a chemical chain reaction or other complex reaction mechanism. For example, the pyrolysis of acetaldehyde () into methane and carbon monoxide proceeds with an order of 1.5 with respect to acetaldehyde: formula_35 The decomposition of phosgene () to carbon monoxide and chlorine has order 1 with respect to phosgene itself and order 0.5 with respect to chlorine: formula_36


title: Rate equation

text: The order of a chain reaction can be rationalized using the steady state approximation for the concentration of reactive intermediates such as free radicals. For the pyrolysis of acetaldehyde, the Rice-Herzfeld mechanism is


title: Rate equation

text: where • denotes a free radical. To simplify the theory, the reactions of the to form a second are ignored.


title: Rate equation

text: The reaction rate equals the rate of the propagation steps which form the main reaction products and CO:


title: Rate equation

text: More complex rate laws have been described as being "mixed order" if they approximate to the laws for more than one order at different concentrations of the chemical species involved. For example, a rate law of the form formula_39 represents concurrent first order and second order reactions (or more often concurrent pseudo-first order and second order) reactions, and can be described as mixed first and second order. For sufficiently large values of [A] such a reaction will approximate second order kinetics, but for smaller [A] the kinetics will approximate first order (or pseudo-first order). As the reaction progresses, the reaction can change from second order to first order as reactant is consumed.


title: Rate equation

text: Another type of mixed-order rate law has a denominator of two or more terms, often because the identity of the rate-determining step depends on the values of the concentrations. An example is the oxidation of an alcohol to a ketone by hexacyanoferrate (III) ion [Fe(CN)] with ruthenate (VI) ion (RuO) as catalyst. For this reaction, the rate of disappearance of hexacyanoferrate (III) is formula_40


title: Rate equation

text: This is zero-order with respect to hexacyanoferrate (III) at the onset of the reaction (when its concentration is high and the ruthenium catalyst is quickly regenerated), but changes to first-order when its concentration decreases and the regeneration of catalyst becomes rate-determining.


title: Rate equation

text: A reaction rate can have a negative partial order with respect to a substance. For example, the conversion of ozone (O) to oxygen follows the rate equation formula_41 in an excess of oxygen. This corresponds to second order in ozone and order (−1) with respect to oxygen.


title: Rate equation

text: When a partial order is negative, the overall order is usually considered as undefined. In the above example, for instance, the reaction is not described as first order even though the sum of the partial orders is formula_42, because the rate equation is more complex than that of a simple first-order reaction.


title: Rate equation

text: A pair of forward and reverse reactions may occur simultaneously with comparable speeds. For example, A and B react into products P and Q and vice versa ("a, b, p", and "q" are the stoichiometric coefficients):


title: Rate equation

text: The reaction rate expression for the above reactions (assuming each one is elementary) can be written as:


title: Rate equation

text: where: "k" is the rate coefficient for the reaction that consumes A and B; "k" is the rate coefficient for the backwards reaction, which consumes P and Q and produces A and B.


title: Rate equation

text: The constants "k" and "k" are related to the equilibrium coefficient for the reaction (K) by the following relationship (set "v"=0 in balance):


title: Rate equation

text: where the reaction starts with an initial concentration of reactant A, <chem>[A]0</chem>, and an initial concentration of 0 for product P at time "t"=0.


title: Rate equation

text: The concentration of A at time "t", formula_49, is related to the concentration of P at time "t", formula_50, by the equilibrium reaction equation:


title: Rate equation

text: The term <chem>[P]0</chem> is not present because, in this simple example, the initial concentration of P is 0.


title: Rate equation

text: These equations allow us to uncouple the system of differential equations, and allow us to solve for the concentration of A alone.


title: Rate equation

text: The derivative is negative because this is the rate of the reaction going from A to P, and therefore the concentration of A is decreasing. To simplify notation, let "x" be formula_49, the concentration of A at time "t". Let formula_56 be the concentration of A at equilibrium. Then:


title: Rate equation

text: A plot of the negative natural logarithm of the concentration of A in time minus the concentration at equilibrium versus time "t" gives a straight line with slope "k" + "k". By measurement of [A] and [P] the values of "K" and the two reaction rate constants will be known.


title: Rate equation

text: If the concentration at the time "t" = 0 is different from above, the simplifications above are invalid, and a system of differential equations must be solved. However, this system can also be solved exactly to yield the following generalized expressions:


title: Rate equation

text: When the equilibrium constant is close to unity and the reaction rates very fast for instance in conformational analysis of molecules, other methods are required for the determination of rate constants for instance by complete lineshape analysis in NMR spectroscopy.


title: Rate equation

text: If the rate constants for the following reaction are formula_63 and formula_64; <chem> A -> B -> C </chem>, then the rate equation is:


title: Rate equation

text: With the individual concentrations scaled by the total population of reactants to become probabilities, linear systems of differential equations such as these can be formulated as a master equation. The differential equations can be solved analytically and the integrated rate equations are


title: Rate equation

text: When a substance reacts simultaneously to give two different products, a parallel or competitive reaction is said to take place.


title: Rate equation

text: <chem> A -> B </chem> and <chem> A -> C </chem>, with constants formula_71 and formula_72 and rate equations formula_73; formula_74 and formula_75


title: Rate equation

text: This can be the case when studying a bimolecular reaction and a simultaneous hydrolysis (which can be treated as pseudo order one) takes place: the hydrolysis complicates the study of the reaction kinetics, because some reactant is being "spent" in a parallel reaction. For example, A reacts with R to give our product C, but meanwhile the hydrolysis reaction takes away an amount of A to give B, a byproduct: <chem>A + H2O -> B </chem> and <chem>A + R -> C </chem>. The rate equations are: formula_80 and formula_81, where formula_82 is the pseudo first order constant.


title: Rate equation

text: The integrated rate equation for the main product [C] is formula_83, which is equivalent to formula_84. Concentration of B is related to that of C through formula_85


title: Rate equation

text: The integrated equations were analytically obtained but during the process it was assumed that formula_86. Therefore, previous equation for [C] can only be used for low concentrations of [C] compared to [A]