title: History of religion

text: From the 15th century to the 19th century, European colonisation resulted in the spread of Christianity to Sub-Saharan Africa, and the Americas, Australia and the Philippines. The invention of the printing press in the 15th century played a major role in the rapid spread of the Protestant Reformation under leaders such as Martin Luther (1483–1546) and John Calvin (1509–1564). Wars of religion broke out, culminating in the Thirty Years' War which ravaged Central Europe between 1618 and 1648. The 18th century saw the beginning of secularisation in Europe, a trend which gained momentum after the French Revolution broke out in 1789. By the late 20th century, religion had declined in most of Europe.


title: History of religion

text: By 2001, people began to use the internet in order to discover or adhere to their religious beliefs. In January 2000, the website beliefnet was established, and by the following year, it had over 1.7 million visitors every month.


title: M-84

text: The M-84 is a Yugoslav third generation main battle tank, a variant of the Soviet T-72. The M-84 is still in service in Croatia, Serbia, Bosnia and Herzegovina and Kuwait.


title: M-84

text: The M-84 is based on the Soviet T-72M (export variant of T-72A) but with many improvements, including introducing domestic fire-control system that T-72M lacked, improved composite armor, and a 1000-hp engine. The M-84 entered service with the Yugoslav People's Army in 1984. The improved M-84A version entered service a few years later. Other variants were introduced later, most being modernization packages.


title: M-84

text: There were about 240 Yugoslav factories which directly participated in the production of the M-84 and about 1,000 others which participated indirectly. Finalist was chosen to be in Đuro Đaković (company) Croatia by Josip Broz Tito, among other proposed manufacturers in Serbia: Goša FOM Smederevska Palanka and Mašinska Industrija Niš that where at that time the biggest producers of locomotives and wagons in Yugoslavia. Biggest manufacturers directly involved in production of M84 main battle tank in SFR Yugoslavia and Federal republic of Yugoslavia among former republics were:


title: M-84

text: Serbian version of the M-84 is the M-84AS was unveiled in 2004. It features a new fire control system, Kontakt-5 ERA armor, AT-11 Sniper anti-tank missiles, Agava-2 thermal sight, and the Shtora defensive suite. It is very similar to the Russian T-90S, both in appearance and in capability. Latest prototype version from Serbia M-84AS1 unveiled in 2017. has new fire control system with domestic laser and radar warning system, RCWS 12.7mm and soft active protection suite with new version of domestic reactive armor - ERA, later modified prototype of same tank unveiled in 2020 has better shaped ERA M19 reactive armour and some new situational awareness equipment including new ammunition.


title: M-84

text: About 150 M-84 tanks were exported to Kuwait. The disintegration of Yugoslavia in the 1990s prevented further exports of the M-84. Sales of M84 including negotiations of contracts with foreign partners were done through Yugoimport SDPR, at that time acting as Yugoslav state agency. Production and delivering was awarded to- and performed by Đuro Đaković.


title: M-84

text: The M-84A is armed with a 125 mm smoothbore cannon derived from the Soviet 2A46. The fume extractor positioned in the middle of the barrel is shielded with a thermal coating that minimizes deformation of the barrel from high temperatures and ensures it is cooled at the same rate during rapid firing. The M-84 uses an automatic loader, which enables it to sustain a firing rate of 8 rounds per minute.


title: M-84

text: The cannon's ammunition is stowed underneath the turret (40 rounds) within the hull of the tank. This concept was inherited from the original Soviet design for T-72 and is both a strength and weakness of the tank. While the lower hull beneath the turret is one of the least likely place to be hit and penetrated by antitank rounds or mines it also means that in the event of penetration and secondary detonation of the ammunition the crew and tank are unlikely to survive the resulting catastrophic explosion.


title: M-84

text: Along with its primary armament, the M-84 is also armed with one 7.62mm coaxial machine gun, and one 12.7mm anti-aircraft gun mounted on the commander's turret.


title: M-84

text: All versions of the M-84 have a crew of three. The commander sits on the right side of the turret, the gunner on the left, and the driver sits centrally at the front end of the vehicle. Like most Soviet derived vehicles, the M-84 series of tanks do not have a manual loader, due to the tank's autoloader system.


title: M-84

text: The basic tank has a cast steel turret with maximal thickness of 410mm; later, in the M-84A version, a segment made out of a non-metal, most likely rubber and boron carbide (see Chobham armour), was sandwiched between layers of steel. The glacis uses laminate armor, glass in plastic resin between two steel plates, in the A version a 16mm steel plate was welded on the glacis. Total armor protection ranges between 550mm-650mm for the glacis and 560mm-700mm for the turret. During the wars in Yugoslavia the M-84's frontal armor proved very effective against any type of AT threat. Side or rear hits often result in a catastrophic ammo explosion.


title: M-84

text: Twelve smoke grenades are positioned in front of the turret in banks of five and seven grenades. Night vision and gunner's sight are positioned on the top-right side of the turret. The M-84 has a search light used in short-range combat situations.


title: M-84

text: The base M-84 engine is a 12-cylinder water-cooled V46-6 diesel engine, rated at 574 kW (780 hp). The improved M-84A has a more powerful, V46-TK 735 kW (1,000 hp) engine. With maximum fuel capacity (1,200 litres) the tank's range is 450 km, and with external fuel tanks, this range can be extended to 650 km.


title: M-84

text: The Croatian-made variants have enhanced power plants. The M-84A4 "Sniper" model has a German-built 820 kW (1,100 hp) engine, while the M-84D has an 895 kW (1,200 hp) engine, the most powerful of all M-84 variants. The M-84D also has greater fuel capacity (1,450 litres).


title: M-84

text: M-84 (Yugoslavia) – The initial version based on the Soviet T-72M and produced between 1984 and 1987. Less than 150 units manufactured.


title: M-84

text: Prior to the Persian Gulf War, Kuwait ordered 170 M-84ABs, 15 M-84ABI ARVs and 15 M-84ABK command tanks, from Yugoslavia. Four M-84A tanks were delivered; however, the Iraqi Army soon captured them after the occupation. Further deliveries were stopped for the duration of the war. The Kuwaiti 35th Al-Shaheed Armored Brigade was equipped with 70 M-84s. During the retaking of the country, the 35th Brigade did not directly take part in battles with Iraqi tanks because of the M-84s similarity to Iraqi T-72 or Asad Babils. The M-84 was however very effective against T-62s and T-55s but some unconfirmed reports claim that a few of them were damaged, but recovered and repaired.


title: M-84

text: During the Ten-Day War, the Yugoslav People's Army (JNA) attempted to regain control over border crossings, airports and other strategic positions in Slovenia. The Slovenian Territorial Defence had no armored units of its own and JNA M-84s were commonly used to break through barricades. Slovenia inherited all the M-84s within its territory, once the ceasefire and Slovenia's independence was accepted.


title: M-84

text: The M-84 saw action in the Battle of Vukovar, where the JNA and Serbian forces deployed large columns of main battle tanks in urban areas without the adequate support of the infantry. Tanks and APCs found themselves extremely exposed and suffered significant losses mainly to RPGs.


title: M-84

text: It was noted by anti tank crews that the M-84s were extremely durable in comparison to other vehicles fielded by the JNA. One account from a team in the Battle of Vukovar noted that a single M-84 took 5 rounds from various launchers and direction with a 6th only knocking out its engine forcing its crew to bail out (its main gun being destroyed by a "lucky" AT shot from an RPG-7).


title: M-84

text: During the War in Bosnia and Herzegovina, M-84s saw little action, the mainstay of all three warring parties being the T-55.


title: M-84

text: At the beginning of the war, JNA units stationed in Bosnia and Herzegovina had passed their equipment to the Army of Republika Srpska (VRS). The VRS had several dozen M-84s, with the Army of Bosnia and Herzegovina managing to capture only three M-84s. A number of M-84 tanks were used during the Siege of Sarajevo, as well as during smaller localized conflicts. The number of M-84 tanks destroyed during the Bosnian war is unknown.


title: M-84

text: The M-84 was used by Yugoslav Ground Forces in Oraovica village during Insurgency in the Preševo Valley.


title: Patron saint

text: A patron saint, patroness saint, patron hallow or heavenly protector is a saint who in Catholicism, Anglicanism, or Eastern Orthodoxy is regarded as the heavenly advocate of a nation, place, craft, activity, class, clan, family, or person.


title: Patron saint

text: Saints often become the patrons of places where they were born or had been active. However, there were cases in Medieval Europe where a city which grew to prominence and obtained for its cathedral the remains or some relics of a famous saint who had lived and was buried elsewhere, thus making them the city's patron saint – such a practice conferred considerable prestige on the city concerned. In Latin America and the Philippines, Spanish and Portuguese explorers often named a location for the saint on whose feast or commemoration day they first visited the place, with that saint naturally becoming the area's patron.


title: Patron saint

text: Occupations sometimes have a patron saint who had been connected somewhat with it, although some of the connections were tenuous. Lacking such a saint, an occupation would have a patron whose acts or miracles in some way recall the profession. For example, when the previously unknown occupation of photography appeared in the 19th century, Saint Veronica was made its patron, owing to how her veil miraculously received the imprint of Christ's face after she wiped off the blood and sweat.


title: Patron saint

text: The veneration or "commemoration" and recognition of patron saints or saints in general is found in Catholicism, Eastern Catholicism, Eastern Orthodoxy, Oriental Orthodoxy, and among some Lutherans and Anglicans. According to the Catholic catechism a person's patron saint, having already attained the beatific vision, is able to intercede with God for their needs.


title: Patron saint

text: It is, however, generally discouraged in most Protestant branches such as Calvinism, where the practice is considered a form of idolatry.


title: Patron saint

text: A canonized saint can be assigned as patron by a venerable tradition, or chosen by election. The saint is considered a special intercessor with God and the proper advocate of a particular locality, occupation, etc., and merits a special form of religious observance. A term in some ways comparable is "titular", which is applicable only to a church or institution.


title: Patron saint

text: Although Islam has no codified doctrine of patronage on the part of saints, it has nevertheless been an important part of both Sunni and Shia Islamic traditions that particularly important classical saints have served as the heavenly advocates for specific Muslim empires, nations, cities, towns, and villages. Martin Lings wrote: "There is scarcely a region in the empire of Islam which has not a Sufi for its Patron Saint." As the veneration accorded saints often develops purely organically in Islamic climates, in a manner different from Catholic and Eastern Orthodox Christianity, "patron saints" are often recognized through popular acclaim rather than through official declaration. Traditionally, it has been understood that the patron saint of a particular place prays for that place's wellbeing and for the health and happiness of all who live therein.


title: Patron saint

text: However, the Wahhabi and Salafi movements within Sunnism have latterly attacked the veneration of saints (as patron or otherwise), which they claim are a form of idolatry or "shirk". More mainstream Sunni clerics have critiqued this argument since Wahhabism first emerged in the 18th century. The critiques notwithstanding, widespread veneration of saints in the Sunni world declined in the 20th century under Wahhabi and Salafi influence.


title: Patron saint

text: In Hinduism, certain sects may devote themselves to the veneration of a saint, such as the Balmiki sect that reveres Valmiki.


title: Patron saint

text: In Buddhism, a bodhisattva ( ; ) or bodhisatva is a person who is on the path towards bodhi ('awakening') or Buddhahood.


title: Patron saint

text: In Mahayana Buddhism, a bodhisattva refers to anyone who has generated "bodhicitta", a spontaneous wish and compassionate mind to attain Buddhahood for the benefit of all sentient beings. Mahayana bodhisattvas are spiritually heroic persons that work to attain awakening and are driven by a great compassion ("mahakaruṇā"). These beings are exemplified by important spiritual qualities such as the "four divine abodes" ("brahmaviharas") of loving-kindness ("metta"), compassion ("karuṇā"), empathetic joy ("mudita") and equanimity ("upekkha") as well as the various bodhisattva "perfections" ("pāramitās") which include "prajñāpāramitā" ("transcendent knowledge" or "perfection of wisdom") and skillful means ("upaya").


title: Patron saint

text: In Theravada Buddhism, the bodhisattva is mainly seen as an exceptional and rare individual. Only a few select individuals are ultimately able to become bodhisattvas (such as Maitreya). Mahayana Buddhism generally understands the bodhisattva path as being open to everyone and Mahayanists encourage all individuals to become bodhisattvas. Spiritually advanced bodhisattvas such as Avalokiteshvara, Maitreya and Manjushri are also widely venerated across the Mahayana Buddhist world and are believed to possess great magical power which they employ to help all living beings.


title: Monosaccharide

text: Monosaccharides (from Greek "monos": single, "sacchar": sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built.


title: Monosaccharide

text: They are usually colorless, water-soluble, and crystalline solids. Contrary to their name (sugars), only some monosaccharides have a sweet taste. Most monosaccharides have the formula (though not all molecules with this formula are monosaccharides).


title: Monosaccharide

text: Examples of monosaccharides include glucose (dextrose), fructose (levulose), and galactose. Monosaccharides are the building blocks of disaccharides (such as sucrose and lactose) and polysaccharides (such as cellulose and starch). The table sugar used in everyday vernacular is itself a disaccharide sucrose comprising one molecule of each of the two monosaccharides D-glucose and D-fructose.


title: Monosaccharide

text: Each carbon atom that supports a hydroxyl group is chiral, except those at the end of the chain. This gives rise to a number of isomeric forms, all with the same chemical formula. For instance, galactose and glucose are both aldohexoses, but have different physical structures and chemical properties.


title: Monosaccharide

text: The monosaccharide glucose plays a pivotal role in metabolism, where the chemical energy is extracted through glycolysis and the citric acid cycle to provide energy to living organisms.


title: Monosaccharide

text: With few exceptions (e.g., deoxyribose), monosaccharides have this chemical formula: (CHO), where conventionally "x" ≥ 3. Monosaccharides can be classified by the number "x" of carbon atoms they contain: triose (3), tetrose (4), pentose (5), hexose (6), heptose (7), and so on.


title: Monosaccharide

text: Glucose, used as an energy source and for the synthesis of starch, glycogen and cellulose, is a hexose. Ribose and deoxyribose (in RNA and DNA, respectively) are pentose sugars. Examples of heptoses include the ketoses, mannoheptulose and sedoheptulose. Monosaccharides with eight or more carbons are rarely observed as they are quite unstable. In aqueous solutions monosaccharides exist as rings if they have more than four carbons.


title: Monosaccharide

text: Simple monosaccharides have a linear and unbranched carbon skeleton with one carbonyl (C=O) functional group, and one hydroxyl (OH) group on each of the remaining carbon atoms. Therefore, the molecular structure of a simple monosaccharide can be written as H(CHOH)(C=O)(CHOH)H, where "n" + 1 + "m" = "x"; so that its elemental formula is CHO.


title: Monosaccharide

text: By convention, the carbon atoms are numbered from 1 to "x" along the backbone, starting from the end that is closest to the C=O group. Monosaccharides are the simplest units of carbohydrates and the simplest form of sugar.


title: Monosaccharide

text: If the carbonyl is at position 1 (that is, "n" or "m" is zero), the molecule begins with a formyl group H(C=O)− and is technically an aldehyde. In that case, the compound is termed an aldose. Otherwise, the molecule has a ketone group, a carbonyl −(C=O)− between two carbons; then it is formally a ketone, and is termed a ketose. Ketoses of biological interest usually have the carbonyl at position 2.


title: Monosaccharide

text: The various classifications above can be combined, resulting in names such as "aldohexose" and "ketotriose".


title: Monosaccharide

text: A more general nomenclature for open-chain monosaccharides combines a Greek prefix to indicate the number of carbons (tri-, tetr-, pent-, hex-, etc.) with the suffixes "-ose" for aldoses and "-ulose" for ketoses. In the latter case, if the carbonyl is not at position 2, its position is then indicated by a numeric infix. So, for example, H(C=O)(CHOH)H is pentose, H(CHOH)(C=O)(CHOH)H is pentulose, and H(CHOH)(C=O)(CHOH)H is pent-3-ulose.


title: Monosaccharide

text: Two monosaccharides with equivalent molecular graphs (same chain length and same carbonyl position) may still be distinct stereoisomers, whose molecules differ in spatial orientation. This happens only if the molecule contains a stereogenic center, specifically a carbon atom that is chiral (connected to four distinct molecular sub-structures). Those four bonds can have any of two configurations in space distinguished by their handedness. In a simple open-chain monosaccharide, every carbon is chiral except the first and the last atoms of the chain, and (in ketoses) the carbon with the keto group.


title: Monosaccharide

text: For example, the triketose H(CHOH)(C=O)(CHOH)H (glycerone, dihydroxyacetone) has no stereogenic center, and therefore exists as a single stereoisomer. The other triose, the aldose H(C=O)(CHOH)H (glyceraldehyde), has one chiral carbon—the central one, number 2—which is bonded to groups −H, −OH, −C(OH)H, and −(C=O)H. Therefore, it exists as two stereoisomers whose molecules are mirror images of each other (like a left and a right glove). Monosaccharides with four or more carbons may contain multiple chiral carbons, so they typically have more than two stereoisomers. The number of distinct stereoisomers with the same diagram is bounded by 2, where "c" is the total number of chiral carbons.


title: Monosaccharide

text: The Fischer projection is a systematic way of drawing the skeletal formula of an acyclic monosaccharide so that the handedness of each chiral carbon is well specified. Each stereoisomer of a simple open-chain monosaccharide can be identified by the positions (right or left) in the Fischer diagram of the chiral hydroxyls (the hydroxyls attached to the chiral carbons).


title: Monosaccharide

text: Most stereoisomers are themselves chiral (distinct from their mirror images). In the Fischer projection, two mirror-image isomers differ by having the positions of all chiral hydroxyls reversed right-to-left. Mirror-image isomers are chemically identical in non-chiral environments, but usually have very different biochemical properties and occurrences in nature.


title: Monosaccharide

text: While most stereoisomers can be arranged in pairs of mirror-image forms, there are some non-chiral stereoisomers that are identical to their mirror images, in spite of having chiral centers. This happens whenever the molecular graph is symmetrical, as in the 3-ketopentoses H(CHOH)(CO)(CHOH)H, and the two halves are mirror images of each other. In that case, mirroring is equivalent to a half-turn rotation. For this reason, there are only three distinct 3-ketopentose stereoisomers, even though the molecule has two chiral carbons.


title: Monosaccharide

text: Distinct stereoisomers that are not mirror-images of each other usually have different chemical properties, even in non-chiral environments. Therefore, each mirror pair and each non-chiral stereoisomer may be given a specific monosaccharide name. For example, there are 16 distinct aldohexose stereoisomers, but the name "glucose" means a specific pair of mirror-image aldohexoses. In the Fischer projection, one of the two glucose isomers has the hydroxyl at left on C3, and at right on C4 and C5; while the other isomer has the reversed pattern. These specific monosaccharide names have conventional three-letter abbreviations, like "Glu" for glucose and "Thr" for threose.


title: Monosaccharide

text: Generally, a monosaccharide with "n" asymmetrical carbons has 2 stereoisomers. The number of open chain stereoisomers for an aldose monosaccharide is larger by one than that of a ketose monosaccharide of the same length. Every ketose will have 2 stereoisomers where "n" > 2 is the number of carbons. Every aldose will have 2 stereoisomers where "n" > 2 is the number of carbons.


title: Monosaccharide

text: These are also referred to as epimers which have the different arrangement of −OH and −H groups at the asymmetric or chiral carbon atoms (this does not apply to those carbons having the carbonyl functional group).


title: Monosaccharide

text: Like many chiral molecules, the two stereoisomers of glyceraldehyde will gradually rotate the polarization direction of linearly polarized light as it passes through it, even in solution. The two stereoisomers are identified with the prefixes - and -, according to the sense of rotation: -glyceraldehyde is dextrorotatory (rotates the polarization axis clockwise), while -glyceraldehyde is levorotatory (rotates it counterclockwise).


title: Monosaccharide

text: The - and - prefixes are also used with other monosaccharides, to distinguish two particular stereoisomers that are mirror-images of each other. For this purpose, one considers the chiral carbon that is furthest removed from the C=O group. Its four bonds must connect to −H, −OH, −C(OH)H, and the rest of the molecule. If the molecule can be rotated in space so that the directions of those four groups match those of the analog groups in -glyceraldehyde's C2, then the isomer receives the - prefix. Otherwise, it receives the - prefix.


title: Monosaccharide

text: In the Fischer projection, the - and - prefixes specifies the configuration at the carbon atom that is second from bottom: - if the hydroxyl is on the right side, and - if it is on the left side.


title: Monosaccharide

text: Note that the - and - prefixes do not indicate the direction of rotation of polarized light, which is a combined effect of the arrangement at all chiral centers. However, the two enantiomers will always rotate the light in opposite directions, by the same amount. See also .


title: Monosaccharide

text: A monosaccharide often switches from the acyclic (open-chain) form to a cyclic form, through a nucleophilic addition reaction between the carbonyl group and one of the hydroxyls of the same molecule. The reaction creates a ring of carbon atoms closed by one bridging oxygen atom. The resulting molecule has a hemiacetal or hemiketal group, depending on whether the linear form was an aldose or a ketose. The reaction is easily reversed, yielding the original open-chain form.


title: Monosaccharide

text: In these cyclic forms, the ring usually has five or six atoms. These forms are called furanoses and pyranoses, respectively—by analogy with furan and pyran, the simplest compounds with the same carbon-oxygen ring (although they lack the double bonds of these two molecules). For example, the aldohexose glucose may form a hemiacetal linkage between the aldehyde group on carbon 1 and the hydroxyl on carbon 4, yielding a molecule with a 5-membered ring, called glucofuranose. The same reaction can take place between carbons 1 and 5 to form a molecule with a ring, called glucopyranose. Cyclic forms with a seven-atom ring (the same of oxepane), rarely encountered, are called heptoses.


title: Monosaccharide

text: For many monosaccharides (including glucose), the cyclic forms predominate, in the solid state and in solutions, and therefore the same name commonly is used for the open- and closed-chain isomers. Thus, for example, the term "glucose" may signify glucofuranose, glucopyranose, the open-chain form, or a mixture of the three.


title: Monosaccharide

text: Cyclization creates a new stereogenic center at the carbonyl-bearing carbon. The −OH group that replaces the carbonyl's oxygen may end up in two distinct positions relative to the ring's midplane. Thus each open-chain monosaccharide yields two cyclic isomers (anomers), denoted by the prefixes α- and β-. The molecule can change between these two forms by a process called mutarotation, that consists in a reversal of the ring-forming reaction followed by another ring formation.


title: Monosaccharide

text: The stereochemical structure of a cyclic monosaccharide can be represented in a Haworth projection. In this diagram, the α-isomer for the pyranose form of a -aldohexose has the −OH of the anomeric carbon below the plane of the carbon atoms, while the β-isomer has the −OH of the anomeric carbon above the plane. Pyranoses typically adopt a chair conformation, similar to that of cyclohexane. In this conformation, the α-isomer has the −OH of the anomeric carbon in an axial position, whereas the β-isomer has the −OH of the anomeric carbon in equatorial position (considering -aldohexose sugars).


title: Richard Roundtree

text: Richard Roundtree (born July 9, 1942) is an American actor. Roundtree is noted as being "the first black action hero" for his portrayal of private detective John Shaft in the 1971 film "Shaft", and its four sequels, released between 1972 and 2019. For his performance in the original film, Roundtree was nominated for the Golden Globe Award for New Star of the Year – Actor in 1972.


title: Richard Roundtree

text: Born July 9, 1942, in New Rochelle, New York, to John and Kathryn Roundtree, Roundtree attended New Rochelle High School; graduating in 1961. During high school, Roundtree played for the school's undefeated and nationally ranked football team. After high school, Roundtree attended Southern Illinois University in Carbondale, Illinois. Roundtree dropped out of college in 1963 to begin his career.


title: Richard Roundtree

text: Roundtree began his professional career around 1963. Roundtree began modeling in the Ebony Fashion Fair after being scouted by Eunice W. Johnson. After his modeling success with the Fashion Fair, Roundtree began modeling for such products as Johnson Products' Duke hair grease and Salem cigarettes. In 1967, Roundtree joined the Negro Ensemble Company. His first role while a part of the company was portraying boxing legend Jack Johnson in the company's production of "The Great White Hope." According to J. E. Franklin, he acted in the Off-Off-Broadway production of her play "Mau Mau Room," by the Negro Ensemble Company Workshop Festival,<ref name="NYPL/Schomburg Center/Negro Ensemble Company"></ref> at St. Mark's Playhouse in 1969, directed by Shauneille Perry.


title: Richard Roundtree

text: Roundtree was a leading man in early 1970s blaxploitation films, his best-known role being detective John Shaft in the action movie, "Shaft" (1971) and its sequels, "Shaft's Big Score!" (1972) and "Shaft in Africa" (1973). Roundtree also appeared opposite Laurence Olivier and Ben Gazzara in "Inchon" (1981). On television, he played the slave Sam Bennett in the 1977 television series "Roots" and Dr. Daniel Reubens on "Generations" from 1989 to 1991. He played another private detective in 1984's "City Heat" opposite Clint Eastwood and Burt Reynolds. Although Roundtree worked throughout the 1990s, many of his films were not well-received, but he found success elsewhere in stage plays.


title: Richard Roundtree

text: During that period, however, he reemerged on the small screen as a cultural icon. On September 19, 1991, Roundtree appeared in an episode of "Beverly Hills, 90210" with Vivica A. Fox. The episode was "Ashes to Ashes", Roundtree playing Robinson Ashe Jr. Roundtree appeared in David Fincher's critically acclaimed 1995 movie "Seven", and in the 2000 "Shaft", again as John Shaft, with Samuel L. Jackson playing the title character, who is described as the original Shaft's nephew. Roundtree guest-starred in several episodes of the first season of "Desperate Housewives" as an amoral private detective. He also appeared in 1997's "George of the Jungle" and played a high-school vice-principal in the 2005 movie, "Brick". His voice was utilized as the title character in the hit PlayStation game "Akuji the Heartless", where Akuji must battle his way out of the depths of hell at the bidding of the Baron.


title: Richard Roundtree

text: Since 2005, Roundtree has appeared in the television series "The Closer" as Colonel D. B. Walter, U.S.M.C. (retired), the father of a sniper, and in "Heroes" as Simone's terminally ill father, Charles Deveaux. Next, Roundtree appeared as Eddie's father-in-law in episodes of "Lincoln Heights". Most recently, Roundtree had a supporting role in the 2008 "Speed Racer" film as a racer-turned-commentator who is an icon and hero to Speed. He also appeared in the two-parter in "Knight Rider" (2008) as the father of FBI Agent Carrie Ravai, and currently co-stars as the father of the lead character on "Being Mary Jane", which has aired on BET since 2013.


title: Richard Roundtree

text: In 2019, Roundtree co-starred in the comedy film "What Men Want", and returned to the role of John Shaft in "Shaft", a sequel to the 2000 film, opposite Samuel L. Jackson and Jessie Usher, who portray John Shaft II and John Shaft III, respectively. This time, Roundtree's character was described as Jackson's character's father, while acknowledging that Roundtree had pretended to be Jackson's Shaft's uncle in the 2000 movie.


title: Richard Roundtree

text: Roundtree has been married twice and has five children. His first marriage was to Mary Jane Grant, whom he married on November 27, 1963. Roundtree and Grant had two children before divorcing in December 1973. He dated actress and TV personality Cathy Lee Crosby shortly thereafter. Roundtree later married Karen M. Ciernia in September 1980; together they had three children. Roundtree and Ciernia divorced in 1998. Roundtree was diagnosed with breast cancer in 1993 and underwent a double mastectomy and chemotherapy.


title: Supply chain

text: In commerce, a supply chain is a network of facilities that procure raw materials, transform them into intermediate goods and then final products to customers through a distribution system. It refers to the network of organizations, people, activities, information, and resources involved in delivering a product or service to a consumer. Supply chain activities involve the transformation of natural resources, raw materials, and components into a finished product and delivering the same to the end customer. In sophisticated supply chain systems, used products may re-enter the supply chain at any point where residual value is recyclable. Supply chains link value chains. Suppliers in a supply chain are often ranked by "tier", with first-tier suppliers supplying directly to the client, second-tier suppliers supplying to the first tier, and so on.


title: Supply chain

text: A typical supply chain begins with the ecological, biological, and political regulation of natural resources, followed by the human extraction of raw material, and includes several production links (e.g., component construction, assembly, and merging) before moving on to several layers of storage facilities of ever-decreasing size and increasingly remote geographical locations, and finally reaching the consumer. At the end of the supply chain, materials and finished products only flow there because of the customer behaviour at the end of the chain; academics Alan Harrison and Janet Godsell argue that "supply chain processes


title: Supply chain

text: should be co-ordinated in order to focus on end customer buying behaviour", and look for "customer responsiveness" as an indicator confirming that materials are able to flow "through a sequence of supply chain processes in order to meet end customer buying behaviour".


title: Supply chain

text: Many of the exchanges encountered in the supply chain take place between varied companies that seek to maximize their revenue within their sphere of interest but may have little or no knowledge or interest in the remaining players in the supply chain. More recently, the loosely coupled, self-organizing network of businesses who cooperate in providing product and service offerings has been called the "extended enterprise", and the use of the term "chain" and the linear structure it appears to represent have been criticised as "harder to relate ... to the way supply networks really operate. A chain is actually a complex and dynamic supply and demand network.


title: Supply chain

text: As part of their efforts to demonstrate ethical practices, many large companies and global brands are integrating codes of conduct and guidelines into their corporate cultures and management systems. Through these, corporations are making demands on their suppliers (facilities, farms, subcontracted services such as cleaning, canteen, security etc.) and verifying, through social audits, that they are complying with the required standard. A lack of transparency in the supply chain can bar consumers from knowledge of where their purchases originated and facilitate socially irresponsible practices. In 2018, the Loyola University Chicago's Supply and Value Chain Center found in a survey that 53% of supply chain professionals considered ethics to be "extremely" important to their organization. Supply-chain managers are under constant scrutiny to secure the best pricing for their resources, which becomes a difficult task when faced with the inherent lack of transparency. Cost benchmarking is one effective method for identifying competitive pricing within the industry. This gives negotiators a solid basis to form their strategy on and drive overall spending down.


title: Supply chain

text: Marshall L. Fisher (1977) asks the question in a key article, "Which is the right supply chain for your product?" Fisher, and also Naylor, Naim and Berry (1999), identify two matching characteristics of supply chain strategy: a combination of "functional" and "efficient", or a combination of "responsive" and "innovative" (Harrison and Godsell).


title: Supply chain

text: Brown "et al." refer to supply chains as either "loosely coupled" or "tightly coupled": These ideas refer to two polar models of collaboration: tightly coupled, or "hard-wired", also known as "linked", collaboration represents a close relationship between a buyer and supplier within the chain, whereas a loosely-coupled link relates to low interdependency between buyer and seller and therefore greater flexibility. The Chartered Institute of Procurement & Supply's professional guidance suggests that the aim of a tightly coupled relationship is to reduce inventory and avoid stock-outs.


title: Supply chain

text: There are a variety of supply-chain models, which address both the upstream and downstream elements of supply-chain management (SCM). The SCOR (Supply-Chain Operations Reference) model, developed by a consortium of industry and the non-profit Supply Chain Council (now part of APICS) became the cross-industry de facto standard defining the scope of supply-chain management. SCOR measures total supply-chain performance. It is a process reference model for supply-chain management, spanning from the supplier's supplier to the customer's customer. It includes delivery and order fulfillment performance, production flexibility, warranty and returns processing costs, inventory and asset turns, and other factors in evaluating the overall effective performance of a supply chain.


title: Supply chain

text: The supply chain can be split into different segments, after which stage in the supply chain process it considers. The earlier stages of a supply chain, such as raw material processing and manufacturing determine their break-even point by considering production costs, relative to market price. The later stages of a supply chain, such as wholesale and retail determine their break-even point by considering transaction costs, relative to market price. Additionally, there are financial costs associated with all the stages of a supply chain model.


title: Supply chain

text: The Global Supply Chain Forum has introduced another supply chain model. This framework is built on eight key business processes that are both cross-functional and cross-firm in nature. Each process is managed by a cross-functional team including representatives from logistics, production, purchasing, finance, marketing, and research and development. While each process interfaces with key customers and suppliers, the processes of customer relationship management and supplier relationship management form the critical linkages in the supply chain.


title: Supply chain

text: The American Productivity and Quality Center (APQC) Process Classification Framework (PCF) SM is a high-level, industry-neutral enterprise process model that allows organizations to see their business processes from a cross-industry viewpoint. The PCF was developed by APQC and its member organizations as an open standard to facilitate improvement through process management and benchmarking, regardless of industry, size, or geography. The PCF organizes operating and management processes into 12 enterprise-level categories, including process groups, and over 1,000 processes and associated activities.


title: Supply chain

text: In the developing country public health setting, John Snow, Inc. has developed the JSI Framework for Integrated Supply Chain Management in Public Health, which draws from commercial sector best practices to solve problems in public health supply chains.


title: Supply chain

text: Similarly, supply chain mapping involves documenting information regarding all participants in an organisation's supply chain and assembling the information as a global map of the organisation's supply network.


title: Supply chain

text: In the 1980s, the term supply-chain management (SCM) was developed to express the need to integrate the key business processes, from end user through original suppliers. Original suppliers are those that provide products, services, and information that add value for customers and other stakeholders. The basic idea behind SCM is that companies and corporations involve themselves in a supply chain by exchanging information about market demand, distribution capacity and production capabilities. Keith Oliver, a consultant at Booz Allen Hamilton, is credited with the term's invention after using it in an interview for the "Financial Times" in 1982. The term was used earlier by Alizamir et al. in 1981.


title: Supply chain

text: If all relevant information is accessible to any relevant company, every company in the supply chain has the ability to help optimize the entire supply chain rather than to sub-optimize based on local optimization. This will lead to better-planned overall production and distribution, which can cut costs and give a more attractive final product, leading to better sales and better overall results for the companies involved. This is one form of vertical integration. Yet, it has been shown that the motives for and performance efficacy of vertical integration differ by global region.


title: Supply chain

text: Incorporating SCM successfully leads to a new kind of competition on the global market, where competition is no longer of the company-versus-company form but rather takes on a supply-chain-versus-supply-chain form.


title: Supply chain

text: The primary objective of SCM is to fulfill customer demands through the most efficient use of resources, including distribution capacity, inventory, and labor. In theory, a supply chain seeks to match demand with supply and do so with minimal inventory. Various aspects of optimizing the supply chain include liaising with suppliers to eliminate bottlenecks; sourcing strategically to strike a balance between lowest material cost and transportation, implementing just-in-time techniques to optimize manufacturing flow; maintaining the right mix and location of factories and warehouses to serve customer markets; and using location allocation, vehicle routing analysis, dynamic programming, and traditional logistics optimization to maximize the efficiency of distribution.


title: Supply chain

text: The term "logistics" applies to activities within one company or organization involving product distribution, whereas "supply chain" additionally encompasses manufacturing and procurement, and therefore has a much broader focus as it involves multiple enterprises (including suppliers, manufacturers, and retailers) working together to meet a customer need for a product or service.


title: Supply chain

text: Starting in the 1990s, several companies chose to outsource the logistics aspect of supply-chain management by partnering with a third-party logistics provider (3PL). Companies also outsource production to contract manufacturers. Technology companies have risen to meet the demand to help manage these complex systems. Cloud-based SCM technologies are at the forefront of next-generation supply chains due to their impact on optimization of time, resources, and inventory visibility. Cloud technologies facilitate work being processed offline from a mobile app which solves the common issue of inventory residing in areas with no online coverage or connectivity.


title: Supply chain

text: Supply chain resilience is "the capacity of a supply chain to persist, adapt, or transform in the face of change". For a long time, the interpretation of resilience in the sense of engineering resilience (= robustness) prevailed in supply chain management, leading to the notion of "persistence". A popular implementation of this idea is given by measuring the "time-to-survive" and the "time-to-recover" of the supply chain, allowing identification of weak points in the system. More recently, the interpretations of resilience in the sense of ecological resilience and social–ecological resilience have led to the notions of "adaptation" and "transformation", respectively. A supply chain is thus interpreted as a social-ecological system that – similar to an ecosystem (e.g. forest) – is able to constantly adapt to external environmental conditions and – through the presence of social actors and their ability to foresight – also to transform itself into a fundamentally new system. This leads to a panarchical interpretation of a supply chain, embedding it into a system of systems, allowing to analyze the interactions of the supply chain with systems that operate at other levels (e.g. society, political economy, planet Earth). For example, these three components of resilience can be discussed for the 2021 Suez Canal obstruction, when a ship blocked the canal for several days. Persistence means to "bounce back"; in our example it is about removing the ship as quickly as possible to allow "normal" operations. Adaptation means to accept that the system has reached to a "new normal" state and to act accordingly; here, this can be implemented by redirecting ships around the African cape or use alternative modes of transport. Finally, transformation means to question the assumptions of globalization, outsourcing, and linear supply chains and to envision alternatives; in this example this could lead to local and circular supply chains.


title: Supply chain

text: Incidents like the 2013 Savar building collapse with more than 1,100 victims have led to widespread discussions about corporate social responsibility across global supply chains. Wieland and Handfield (2013) suggest that companies need to audit products and suppliers and that supplier auditing needs to go beyond direct relationships with first-tier suppliers (those who supply the main customer directly). They also demonstrate that visibility needs to be improved if the supply cannot be directly controlled and that smart and electronic technologies play a key role to improve visibility. Finally, they highlight that collaboration with local partners, across the industry and with universities is crucial to successfully manage social responsibility in supply chains. This incident also highlights the need to improve workers safety standards in organizations. Hoi and Lin (2012) note that corporate social responsibility can influence the enacting of policies that can improve occupational safety and health management in organizations. In fact, international organizations with presence in other nations have a responsibility to ensure that workers are well protected by policies in an organization to avoid safety related incidents.


title: Supply chain

text: Many agribusinesses and food processors source raw materials from smallholder farmers. This is particularly true in certain sectors, such as coffee, cocoa and sugar. Over the past 20 years, there has been a shift towards more traceable supply chains. Rather than purchasing crops that have passed through several layers of collectors, firms are now sourcing directly from farmers or trusted aggregators. The drivers for this change include concerns about food safety, child labor and environmental sustainability as well as a desire to increase productivity and improve crop quality.


title: Supply chain

text: In October 2009, the European Commission issued a "Communication" concerning "a better functioning food supply chain in Europe", addressing the three sectors of the European economy which comprise the food supply chain: agriculture, food processing industries, and the distribution sectors. An earlier interim report on food prices (published in December 2008) had already raised concerns about the food supply chain. Arising out of the two reports, the Commission established a "European Food Prices Monitoring Tool", an initiative developed by Eurostat and intended to "increase transparency in the food supply chain".


title: Supply chain

text: In March 2022 the Commission noted "the need for EU agriculture and food supply chains to become more resilient and sustainable".


title: Supply chain

text: Supply chain security has become particularly important in recent years. As a result, supply chains are often subject to global and local regulations. In the United States, several major regulations emerged in 2010 that have had a lasting impact on how global supply chains operate. These new regulations include the Importer Security Filing (ISF) and additional provisions of the Certified Cargo Screening Program. EU's draft supply chain law are due diligence requirements to protect human rights and the environment in the supply chain.


title: Supply chain

text: With the increasing globalization and easier access to different kinds of alternative products in today's markets, the importance of product design to generating demand is more significant than ever. In addition, as supply, and therefore competition, among companies for the limited market demand increases and as pricing and other marketing elements become less distinguishing factors, product design likewise plays a different role by providing attractive features to generate demand. In this context, demand generation is used to define how attractive a product design is in terms of creating demand. In other words, it is the ability of a product's design to generate demand by satisfying customer expectations. But product design affects not only demand generation but also manufacturing processes, cost, quality, and lead time. The product design affects the associated supply chain and its requirements directly, including manufacturing, transportation, quality, quantity, production schedule, material selection, production technologies, production policies, regulations, and laws. Broadly, the success of the supply chain depends on the product design and the capabilities of the supply chain, but the reverse is also true: the success of the product depends on the supply chain that produces it.


title: Supply chain

text: Since the product design dictates multiple requirements on the supply chain, as mentioned previously, then once a product design is completed, it drives the structure of the supply chain, limiting the flexibility of engineers to generate and evaluate different (and potentially more cost-effective) supply-chain alternatives.


title: BMW 2 Series

text: The BMW 2 Series is a range of subcompact executive cars (C-segment) manufactured by BMW since 2014. The 2 Series was created when BMW spun-off the 2-door models (coupé and convertible) of the BMW 1 Series into a separate series.


title: BMW 2 Series

text: The 2 Series was first launched as a 2-door coupé and convertible, both based on a rear-wheel drive platform. A year later, the Active Tourer 5-seat compact MPV body style was added, based on the unrelated front-wheel drive platform shared with the Mini Hatch (F55/56/57). This was followed by a 7-seat version called the Gran Tourer. In 2019, the Gran Coupé fastback sedan joined the 2 Series family as a front-wheel drive vehicle based on the 1 Series hatchback and has been marketed as a 4-door coupe. In 2021, BMW released the second-generation 2-door coupé, rear-wheel drive 2 Series in July 2021.


title: BMW 2 Series

text: The BMW M2 is the high-performance version of the 2 Series 2-door coupé. The first generation of the M2 is the F87 coupé and is powered by turbocharged straight-six engines.


title: BMW 2 Series

text: The first-generation 2 Series is a rear-wheel-drive 2-door coupé (F22 model code), and 2-door convertible (F23 model code). This generation has been in production since November 2013 as the successor to the E82 1 Series coupé and E88 1 Series convertible. It is currently produced in Leipzig, previously alongside the F20 1 Series hatchback range.


title: BMW 2 Series

text: The coupé version of the 2 Series is used as the basis of the high performance F87 M2 model. The model is powered by the BMW N55 and BMW S55 turbocharged inline-six engines.


title: BMW 2 Series

text: The second-generation 2 Series coupé was revealed in July 2021 as the successor to the F22 2 Series coupé and convertible. Remaining a rear-wheel-drive-based model, the G42 is built on the CLAR platform with a roughly 50:50 weight distribution and shares many mechanical components and engine options with the G20 3 Series and G22 4 Series. Unlike its predecessor, the second-generation 2 Series coupé is no longer available with a manual transmission and not complemented with a convertible body style. The launch models consist of the mild hybrid diesel engine 220d, the petrol engine 220i and 230i and the top M240i xDrive. The G42 2 Series will be exclusively produced in BMW's San Luis Potosí plant in Mexico. The G42 is the first BMW vehicle designed by BMW of Mexico. Production of the G42 2 Series commenced on 2 September 2021.


title: BMW 2 Series

text: The BMW 2 Series Active Tourer is a five-door, two-row compact MPV produced since 2014. The vehicle is built on the front-wheel drive-based UKL2 platform with an optional all-wheel drive ("xDrive"). It is the first BMW-branded model to not use the rear-wheel drive configuration. A longer version with three-row seating called the BMW 2 Series Gran Tourer was released shortly after in 2015.


title: BMW 2 Series

text: BMW revealed a four-door sedan variant under the 2 Series range in October 2019 as the BMW 2 Series Gran Coupé. It is built on the front-wheel drive UKL2 platform like the Active Tourer (F45) and Gran Tourer (F46). In markets where the vehicle is being sold, it is the smallest four-door sedan offered by BMW, except in China and Mexico where the smaller F52 1 Series sedan is offered.


title: Arak (drink)

text: Arak or araq () is a distilled Levantine spirit of the anise drinks family. It is translucent and unsweetened.


title: Arak (drink)

text: Arak evolved from the Arab invention of alembic distillation in the 12th century. As the vast majority of Arabs were Muslim at that time, the original usage of the distilled alcohol might have been for the production of perfumes and kohl, a cosmetic. However, the distribution of arak and its derivatives – ranging from rakija in the Balkans to arrack in Indonesia and Malaysia – closely follows the pattern of the Arab-Islamic conquests, and in each of these locales the distilled alcohol is used as a beverage.


title: Arak (drink)

text: Arak is traditionally made of only two ingredients, grapes and aniseed. Aniseeds are the seeds of the anise plant, and when crushed, their oil provides arak with a slight licorice taste.


title: Arak (drink)

text: Its pronunciation varies depending on local varieties of Arabic: , . Arak is not to be confused with the similarly named liquor, arrack (which in some cases, such as in Indonesia—especially Bali—also goes by the name arak). Another similar-sounding word is "aragh", which in Armenia, Iran, Azerbaijan, Georgia and Iraq is the colloquial name of vodka, and not an aniseed-flavored drink. Rakı, mastika, and ouzo are aniseed-flavored alcoholic drinks, related to arak, popular in Turkey, North Macedonia, Bulgaria, Cyprus and Greece respectively.


title: Arak (drink)

text: Arak is the traditional alcoholic beverage in Western Asia, especially in the Eastern Mediterranean countries of Lebanon, Israel, Palestine, Syria, and Jordan.


title: Arak (drink)

text: Arak is a stronger flavored liquor, and is usually mixed in proportions of approximately one part arak to two parts water in a traditional Eastern Mediterranean water vessel called an "ibrik" (Arabic: ""). The mixture is then poured into ice-filled cups, usually small, but can also be consumed in regular sized cups. This dilution causes the clear liquor to turn a translucent milky-white color; this is because anethole, the essential oil of anise, is soluble in alcohol but not in water. This results in an emulsion whose fine droplets scatter the light and turn the liquid translucent, a phenomenon known as louching. Arak is commonly served with mezza, which may include dozens of small traditional dishes. In general, arak drinkers prefer to consume it this way, rather than alone. It is also consumed with raw meat dishes (e.g. kibbeh nayyeh in Lebanon and çiğ köfte in Turkey) or barbecues, along with dishes flavored with "toum" (garlic sauce).


title: Arak (drink)

text: If ice is added to the drinking vessel before the water, the result is the formation of an aesthetically unpleasant layer on the surface of the drink, because the ice causes the oils to solidify. If water is added first, the ethanol causes the fat to emulsify, leading to the characteristic milky color. To avoid the precipitation of the anise (instead of an emulsion), drinkers prefer not to reuse a glass which has contained arak. In restaurants, when a bottle of arak is ordered, the waiter will usually bring a number of glasses for each drinker along with it for this reason.


title: Arak (drink)

text: Manufacturing begins with the vineyards, and quality grapevines are the key to making good arak. The vines should be very mature and usually of a golden color. Instead of being irrigated, the vineyards are left to the care of the Mediterranean climate and make use of the natural rain and sun. The grapes, which are harvested in late September and early October, are crushed and put in barrels together with the juice (in Arabic "el romeli") and left to ferment for three weeks. Occasionally the whole mix is stirred to release the CO.


title: Arak (drink)

text: Numerous types of stills exist, most usually made of stainless steel or copper. Pot and column stills are two types; which will affect the final taste and specificity of the arak. The authentic copper stills with a Moorish shape are the most sought after.


title: Arak (drink)

text: The alcohol collected in the first distillation undergoes a second distillation, but this time it is mixed with aniseed. The ratio of alcohol to aniseed may vary and it is one of the major factors in the quality of the final product. The finished product is produced during a final distillation which takes place at the lowest possible temperature. For a quality arak, the finished spirit is then aged in clay amphoras to allow the angel's share to evaporate. The liquid remaining after this step is the most suitable for consumption.


title: Arak (drink)

text: Arak made from various kinds of fruit based liqueurs as well as from wine is commonly produced as moonshine.


title: Fayetteville, North Carolina

text: Fayetteville () is a city in and the county seat of Cumberland County, North Carolina, United States. It is best known as the home of Fort Bragg, a major U.S. Army installation northwest of the city.


title: Fayetteville, North Carolina

text: Fayetteville has received the All-America City Award from the National Civic League three times. As of the 2020 census it had a population of 208,501, It is the 6th-largest city in North Carolina. Fayetteville is in the Sandhills in the western part of the Coastal Plain region, on the Cape Fear River.


title: Fayetteville, North Carolina

text: With a population in 2020 of 529,252 people, the Fayetteville metropolitan area is the largest in southeastern North Carolina, and the fifth-largest in the state. Suburban areas of metro Fayetteville include Fort Bragg, Hope Mills, Spring Lake, Raeford, Pope Field, Rockfish, Stedman, and Eastover.


title: Fayetteville, North Carolina

text: The area of present-day Fayetteville was historically inhabited by various Siouan Native American peoples, such as the Eno, Shakori, Waccamaw, Keyauwee, and Cape Fear people. They followed successive cultures of other indigenous peoples in the area for more than 12,000 years.


title: Fayetteville, North Carolina

text: After the violent upheavals of the Yamasee War and Tuscarora Wars during the second decade of the 18th century, the colonial government of North Carolina encouraged colonial settlement along the upper Cape Fear River, the only navigable waterway entirely within the colony. Two inland settlements, Cross Creek and Campbellton, were established by Scots from Campbeltown, Argyll and Bute, Scotland.


title: Fayetteville, North Carolina

text: Merchants in Wilmington wanted a town on the Cape Fear River to secure trade with the frontier country. They were afraid people would use the Pee Dee River and transport their goods to Charleston, South Carolina. The merchants bought land from Newberry in Cross Creek. Campbellton became a place where poor whites and free blacks lived, and gained a reputation for lawlessness.


title: Fayetteville, North Carolina

text: In 1783, Cross Creek and Campbellton united, and the new town was incorporated as Fayetteville in honor of Gilbert du Motier, Marquis de Lafayette, a French military hero who significantly aided the American forces during the war. Fayetteville was the first city to be named in his honor in the United States. Lafayette visited the city on March 4 and 5, 1825, during his grand tour of the United States.


title: Fayetteville, North Carolina

text: The local region was heavily settled by Scots in the mid/late 1700s, and most of these were Gaelic-speaking Highlanders. The vast majority of Highland Scots, recent immigrants, remained loyal to the British government and rallied to the call to arms from the Royal Governor. Despite this, they were eventually defeated by a larger Revolutionary force at the Battle of Moore's Creek Bridge. The area also included a number of active Revolutionaries.


title: Fayetteville, North Carolina

text: In late June 1775, residents drew up the "Liberty Point Resolves," which preceded the Declaration of Independence by a little more than a year. It said,


title: Fayetteville, North Carolina

text: "This obligation to continue in full force until a reconciliation shall take place between Great Britain and America, upon constitutional principles, an event we most ardently desire; and we will hold all those persons inimical to the liberty of the colonies, who shall refuse to subscribe to this Association; and we will in all things follow the advice of our General Committee respecting the purposes aforesaid, the preservation of peace and good order, and the safety of individual and private property." Robert Rowan, who apparently organized the group, signed first.


title: Fayetteville, North Carolina

text: Robert Rowan (circa 1738–1798) was one of the area's leading public figures of the 18th century. A merchant and entrepreneur, he settled in Cross Creek in the 1760s. He served as an officer in the French and Indian War, as sheriff, justice and legislator, and as a leader of the Patriot cause in the Revolutionary War. Rowan Street and Rowan Park in Fayetteville and a local chapter of the Daughters of the American Revolution are named for him, though Rowan County (founded in 1753) was named for his uncle, Matthew Rowan.


title: Fayetteville, North Carolina

text: Flora MacDonald (1722–1790), a Scots Highland woman known for aiding Bonnie Prince Charlie after his Highlander army's defeat at Culloden in 1746, lived in North Carolina for about five years. She was a staunch Loyalist and aided her husband to raise the local Scots to fight for the King against the Revolution.


title: Fayetteville, North Carolina

text: Seventy-First Township in western Cumberland County (now a part of Fayetteville) is named for a British regiment during the American Revolution – the 71st Regiment of Foot or "Fraser's Highlanders", as they were first called.


title: Fayetteville, North Carolina

text: Fayetteville had what is sometimes called its "golden decade" during the 1780s. It was the site in 1789 for the state convention that ratified the U.S. Constitution, and for the General Assembly session that chartered the University of North Carolina at Chapel Hill. Fayetteville lost out to the future city of Raleigh in the bid to become the permanent state capital.


title: Fayetteville, North Carolina

text: In 1793, the Fayetteville Independent Light Infantry formed and is still active as a ceremonial unit. It is the second-oldest militia unit in the country.


title: Fayetteville, North Carolina

text: Henry Evans (circa 1760–1810), a free black preacher, is locally known as the "Father of Methodism" in the area. Evans was a shoemaker by trade and a licensed Methodist preacher. He met opposition from whites when he began preaching to slaves in Fayetteville, but he later attracted whites to his services. He is credited with building the first church in town, called the African Meeting House, in 1796. Evans Metropolitan AME Zion Church is named in his honor.


title: Fayetteville, North Carolina

text: Fayetteville had 3,500 residents in 1820, but Cumberland County's population still ranked as the second most urban in the state, behind New Hanover County (Wilmington). Its "Great Fire" of 1831 was believed to be one of the worst in the nation's history, despite no deaths being associated with the incident. Hundreds of homes and businesses and most of the best-known public buildings were lost, including the old "State House". Fayetteville leaders moved quickly to help the victims and rebuild the town.


title: Fayetteville, North Carolina

text: There was no point in rebuilding the State House, since the state government was firmly installed in Raleigh. On its site the city built a Market House, recreating the city around it just as it had previously surrounded the State House. The new building had a covered area under which business could be conducted, since every store in Fayetteville had been destroyed in the fire. Completed in 1832, it became the administrative building of the town and county. It was a town market until 1906, and served as Fayetteville Town Hall until 1907. Currently (2020) it is a local history museum.


title: Fayetteville, North Carolina

text: In March 1865, Gen. William T. Sherman and his 60,000-man army attacked Fayetteville and destroyed the Confederate arsenal (designed by the Scottish architect William Bell). Sherman's troops also destroyed foundries and cotton factories, and the offices of "The Fayetteville Observer". Not far from Fayetteville, Confederate and Union troops engaged in the last cavalry battle of the Civil War, the Battle of Monroe's Crossroads.


title: Fayetteville, North Carolina

text: Downtown Fayetteville was the site of a skirmish, as Confederate Lt. Gen. Wade Hampton and his men surprised a cavalry patrol, killing 11 Union soldiers and capturing a dozen on March 11, 1865.


title: Fayetteville, North Carolina

text: During the late nineteenth century, North Carolina adopted Jim Crow laws that imposed racial segregation.


title: Fayetteville, North Carolina

text: Cumberland County's population grew rapidly in the post-World War II years, with its 43% increase in the 1960s the largest in any of North Carolina's 100 counties. Construction was fast-paced as shopping developments and suburban subdivisions began to spread outside the Fayetteville city limits toward Fort Bragg and Pope Air Force Base. The Fayetteville and Cumberland County school systems moved toward integration gradually, beginning in the early 1960s; busing brought about wider-scale student integration in the 1970s.


title: Fayetteville, North Carolina

text: Segregation of public facilities continued. Marches and sit-ins during the Civil Rights Movement, with students from Fayetteville State Teachers College (now Fayetteville State University) at the forefront, led to the end of whites-only service at restaurants and segregated seating in theaters. Blacks and women gained office in significant numbers, from the late 1960s and on into the early 1980s.


title: Fayetteville, North Carolina

text: The Vietnam Era was a time of change in the Fayetteville area. From 1966 to 1970, more than 200,000 soldiers trained at Fort Bragg before leaving for Vietnam. This buildup stimulated area businesses. Anti-war protests in Fayetteville drew national attention because of Fort Bragg, in a city that generally supported the war. Anti-war groups invited the actress and activist Jane Fonda to Fayetteville to participate in three anti-war events. The era also saw an increase in crime and drug addiction, especially along Hay Street, with media giving the city the nickname "Fayettenam". At this time, Fayetteville also made headlines after Army doctor Jeffrey R. MacDonald murdered his pregnant wife and two daughters in their Ft. Bragg home in 1970; the book and movie "Fatal Vision" were based on these events.


title: Fayetteville, North Carolina

text: To combat the dispersal of suburbanization, Fayetteville has worked to redevelop its downtown through various revitalization projects; it has attracted large commercial and defense companies such as Purolator, General Dynamics and Wal-Mart Stores and Distribution Center. Development of the Airborne & Special Operations Museum, Fayetteville Area Transportation Museum, Fayetteville Linear Park, and Fayetteville Festival Park, which opened in late 2006, have added regional attractions to the center.


title: Fayetteville, North Carolina

text: In the first decade of the 21st century, the towns and rural areas surrounding Fayetteville had rapid growth. Suburbs such as Hope Mills, Raeford and Spring Lake had increases in population.


title: Fayetteville, North Carolina

text: In 2005, Congress passed the Base Realignment and Closure (BRAC) Act, resulting in several new commands relocating to Fort Bragg. These include the U.S. Army Forces Command (FORSCOM) and U.S. Army Reserve Command, both of which relocated from Fort McPherson in Atlanta. More than 30,000 people were expected to relocate to the area with associated businesses and families. FORSCOM awards over $300 billion in contracts annually.


title: Fayetteville, North Carolina

text: In the November/December 2009 issue of "Where to Retire", the magazine named Fayetteville as one of the best places to retire in the United States for military retirements.


title: Fayetteville, North Carolina

text: In April 2019, a report by GoBankingRates (which analyzed data from 175 American cities) listed Fayetteville as one of the top ten American cities at risk of a serious housing crash. 26.8% of home mortgages in Fayetteville were listed as being "under water", while the median home value was listed as $108,000.


title: Fayetteville, North Carolina

text: In December 2015, Fayetteville unveiled the Guinness World Record for the biggest Christmas stocking, weighing approximately , and measuring 74.5 x 139 feet.


title: Fayetteville, North Carolina

text: Several U.S. Army airborne units are stationed at Fort Bragg, most prominently the XVIII Airborne Corps HQ, the 82nd Airborne Division, the United States Army Special Operations Command, the 1st Special Forces Command (Airborne), and the United States Army John F. Kennedy Special Warfare Center and School.


title: Fayetteville, North Carolina

text: Fort Bragg was the home of the Field Artillery at the onset of World War II. All the Army's artillery units east of the Mississippi River were based at the post, about 5,000 men in all. Soldiers tested the Army's new bantam car, which was soon to be known as the Jeep, although most of the power to move artillery still came from horses and burros. On September 12, 1940, the Army contracted to expand the post, bringing the 9th Infantry Division to Fort Bragg.


title: Fayetteville, North Carolina

text: The mission of Pope Field is to provide airlift to American armed forces and to humanitarian missions flown all over the world. Pope Field particularly provides air transportation for the 82nd Airborne, among other airborne units on Fort Bragg.


title: Fayetteville, North Carolina

text: All of Pope's fighter jet squadrons have been relocated to Moody AFB, Georgia. The main entity at Pope is now the Air Force Reserve, although they still have a small amount of active personnel.


title: Fayetteville, North Carolina

text: In September 2008, Fayetteville annexed 85% of Ft. Bragg, bringing the population of the city to 206,000. Ft. Bragg retains its own police, fire, and EMS services. Fayetteville hopes to attract large retail businesses to the area using the new population figures.


title: Fayetteville, North Carolina

text: On September 5, 2008, Cumberland County announced it was the "World's First Sanctuary for Soldiers and Their Families"; it marked major roads with blue and white "Sanctuary" signage. Within the county, soldiers were to be provided with local services, ranging from free childcare to job placement for soldiers' spouses.


title: Fayetteville, North Carolina

text: Five hundred volunteers have signed up to watch over military families. They were recruited to offer one-to-one services; member businesses will also offer discounts and preferential treatments. "Time" magazine recognized Fayetteville for its support of military families and identified it as "America's Most Pro-Military Town".


title: Fayetteville, North Carolina

text: The city limits extend west to the Hoke boundary. It is bordered on the north by the town of Spring Lake.


title: Fayetteville, North Carolina

text: According to the United States Census Bureau, Fayetteville has a total area of , of which is land and is water. The total area is 1.926% water.


title: Fayetteville, North Carolina

text: Fayetteville is in the Sandhills of North Carolina, which are between the coastal plain to the southeast and the Piedmont to the northwest. The city is built on the Cape Fear River, a river that originates in Haywood and empties into the Atlantic Ocean. Carver's Falls, measuring wide and two stories tall, is on Carver Creek, a tributary of the Cape Fear, just northeast of the city limits. Cross Creek rises on the west side of Fayetteville and flows through to the east side of Fayetteville into the Cape Fear River.


title: Fayetteville, North Carolina

text: Fayetteville is located in the humid subtropical climate (Köppen climate classification "Cfa") zone, with mostly moderate temperatures year round. Winters are mild, but can get cool with snow occurring a few days per year. Summers are hot with levels of humidity which can cause spontaneous thunderstorms and rain showers. Temperature records range from on February 13, 1899 to on August 21, 1983, which was the highest temperature ever recorded in the State of North Carolina. On April 16, 2011, Fayetteville was struck by an EF3 tornado during North Carolina's largest tornado outbreak. Surrounding areas such as Sanford, Dunn and Raleigh were also affected.


title: Fayetteville, North Carolina

text: As of the 2020 United States census, there were 208,501 people, 82,087 households, and 46,624 families residing in the city.


title: Fayetteville, North Carolina

text: As of the census of 2010, there were 200,564 people, 78,274 households, and 51,163 families residing in the city. The population density was 1,401 people per square mile (541.1/km). There were 87,005 housing units at an average density of 230.3 units/km (596.3 persons/sq mi). The racial composition of the city was 45.7% White, 41.9% Black or African American, 2.6% Asian American, 1.1% Native American, 0.4% Native Hawaiian or Other Pacific Islander, 3.3% some other race, and 4.9% two or more races. 10.1% of the population were Hispanic or Latino of any race.


title: Fayetteville, North Carolina

text: There were 78,274 households, out of which 36.7% had children under the age of 18 living with them, 41.3% were headed by married couples living together, 19.5% had a female householder with no husband present, and 34.6% were non-families. 28.7% of all households were made up of individuals, and 7.3% were someone living alone who was 65 years of age or older. The average household size was 2.45, and the average family size was 3.02.


title: Fayetteville, North Carolina

text: In the city the population was spread out, with 25.8% under the age of 18, 14.4% from 18 to 24, 28.5% from 25 to 44, 21.5% from 45 to 64, and 9.7% who were 65 years of age or older. The median age was 29.9 years. For every 100 females, there were 93.6 males. For every 100 females age 18 and over, there were 90.5 males.


title: Fayetteville, North Carolina

text: In 2013, the estimated median annual income for a household in the city was $44,924, and the median income for a family was $49,608. Male full-time workers had a median income of $37,371 versus $32,208 for females. The per capita income for the city was $23,362. 18.4% of the population and 16.2% of families were below the poverty line. 27.1% of those under the age of 18 and 9.8% of those 65 and older were living below the poverty line.


title: Fayetteville, North Carolina

text: On September 30, 2005, Fayetteville annexed and 46,000 residents. Some affected residents and developers challenged the annexation in the courts, but were ultimately unsuccessful. The exception was the Gates Four neighborhood which won its case against annexation despite the annexation of all surrounding neighborhoods.


title: Fayetteville, North Carolina

text: Founded in Wade in 1758, Old Bluff Presbyterian Church is one of the oldest churches in the Upper Cape Fear Valley. The fourth Sunday of September each year is the annual Old Bluff Reunion; it is open to the public. Bluff Presbyterian Church maintains a detailed history at its website.


title: Fayetteville, North Carolina

text: Hundreds of houses of worship have been established in and around Cumberland County, including Catholic, Baptist, Pentecostal, Methodist and Presbyterian churches, which have the largest congregations. Fayetteville is also home to Congregation Beth Israel, formed in 1910 by the Jewish families of Fayetteville.


title: Fayetteville, North Carolina

text: Fayetteville is home to St. Patrick Church, the oldest Catholic parish in the state, dating back to the 18th century.


title: Fayetteville, North Carolina

text: The Masjid Omar ibn Sayyid mosque was named after Omar ibn Said, an African Muslim who was jailed as a fugitive slave and sold in Fayetteville in the 19th century. Visitors to the mosque can find historical information about him and the Muslim community. Additionally, a historical marker to ibn Said was cast along Murchison Road in 2010, the first roadside in North Carolina to recognize a Muslim.


title: Fayetteville, North Carolina

text: Fort Bragg is the backbone of the county's economy. Fort Bragg and Pope Field pump about $4.5 billion a year into the region's economy, making Fayetteville one of the best retail markets in the country. Fayetteville serves as the region's hub for shops, restaurants, services, lodging, health care and entertainment.


title: Fayetteville, North Carolina

text: As of March 2019 Fayetteville reflected an unemployment rate of 5.2%, which is higher than the national average of 3.8% and the North Carolina average of 4%.


title: Fayetteville, North Carolina

text: According to the Fayetteville 2018 Comprehensive Annual Financial Report, the top employers in the city are:


title: Fayetteville, North Carolina

text: The Fayetteville area has a large and growing defense industry and was ranked in the top five areas in US for 2008, 2010, 2011 by a trade publication. Eight of the ten top American defense contractors are located in the area, including Lockheed Martin, Boeing, Northrop Grumman, General Dynamics, and L-3 Communications.


title: Fayetteville, North Carolina

text: The city hosts Partnership for Defense Initiatives (PDI), a trade association promoting defense contractors.


title: Fayetteville, North Carolina

text: Cumberland County Schools' headquarters are located in Fayetteville, and the schools serve all cities and towns of the county. CCS operates a total of 87 schools: 53 elementary schools, 16 middle schools, 15 high schools and 9 Alternative and Specialty schools, including 1 year-round classical, 1 evening academy, 1 web academy and 2 special schools. Cumberland County Schools is the fourth-largest school system in the state and 78th-largest in the country.


title: Fayetteville, North Carolina

text: Fayetteville Regional Airport is served by five regional carriers that provide daily and seasonal passenger services to three major airline hubs within the United States. An additional regional carrier and several fixed-base operators offer further services for both passenger and general aviation operations. Landmark Aviation also provides services for passenger and general aviation traffic at the Fayetteville Regional Airport.


title: Fayetteville, North Carolina

text: The Fayetteville Area System of Transit (FAST) serves the Fayetteville and Spring Lake regions, with ten bus routes and two shuttle routes. FAST operates thirteen fixed bus routes within the city of Fayetteville. Service is between the hours of 5:45 am and 10:30 pm on weekdays, with reduced hours on Saturdays and no Sunday service. Most routes begin and end at the Transfer Center at 147 Old Wilmington Road in Fayetteville. Other transfer points are located at University Estates, Cross Creek Mall, Veterans Administration Medical Center, Bunce and Cliffdale Rds and Cape Fear Valley Medical Center.


title: Fayetteville, North Carolina

text: The Atlantic Coast Line Railroad Station, built in 1911, provides daily Amtrak service with northbound and southbound routes leading to points along the East Coast.


title: Clomifene

text: Clomifene, also known as clomiphene, is a medication used to treat infertility in women who do not ovulate, including those with polycystic ovary syndrome. Use results in a greater chance of twins. It is taken by mouth once a day, with a course of treatment that usually lasts for five days.


title: Clomifene

text: Common side effects include pelvic pain and hot flashes. Other side effects can include changes in vision, vomiting, trouble sleeping, ovarian cancer, and seizures. It is not recommended in people with liver disease or abnormal vaginal bleeding of unknown cause or who are pregnant. Clomifene is in the selective estrogen receptor modulator (SERM) family of medication and is a nonsteroidal medication. It works by causing the release of GnRH by the hypothalamus, and subsequently gonadotropin from the anterior pituitary.


title: Clomifene

text: Clomifene was approved for medical use in the United States in 1967. It is on the World Health Organization's List of Essential Medicines, under the category "Ovulation inducers" (Complementary List). Its introduction began the era of assisted reproductive technology.


title: Clomifene

text: Clomifene (particularly the purified enclomiphene isomer) has also been found to have a powerful ability to boost or restore testosterone levels in hypogonadal men.


title: Clomifene

text: Clomifene is one of several alternatives for ovulation induction in those who are infertile due to anovulation or oligoovulation. Evidence is lacking for the use of clomifene in those who are infertile without a known reason. In such cases, studies have observed a clinical pregnancy rate 5.6% per cycle with clomifene treatment vs. 1.3%–4.2% per cycle without treatment.


title: Clomifene

text: Proper timing of the drug is important; it should be taken starting on about the fifth day of the cycle, and there should be frequent intercourse.


title: Clomifene

text: Repeat dosing: This 5-day treatment course can be repeated every 30 days. The dosage may be increased by 50-mg increments in subsequent cycles until ovulation is achieved. It is not recommended by the manufacturer to use clomifene for more than 6 cycles.


title: Clomifene

text: It is no longer recommended to perform an ultrasound examination to exclude any significant residual ovarian enlargement before each new treatment cycle.


title: Clomifene

text: Clomifene has also been used with other assisted reproductive technology to increase success rates of these other modalities.


title: Clomifene

text: Clomifene is sometimes used in the treatment of male hypogonadism as an alternative to testosterone replacement therapy. The medication has been used at a dosage of 20 to 50 mg three times per week to once daily for this indication. It has been found to increase testosterone levels by 2- to 2.5-times in hypogonadal men at such dosages. Despite the use of questionnaires in testosterone replacement comparator trials being called into question, clomifene's lower cost, therapeutic benefits, and greater value towards hypogonadism improvement have been noted.


title: Clomifene

text: Clomifene consists of two stereoisomers in equal proportion: enclomifene and zuclomifene. Zuclomifene has pro-estrogenic properties, whereas enclomifene is pro-androgenic, i.e. it promotes testosterone production through stimulation of the HPG axis. For this reason, purified enclomifene isomer has been found to be twice as effective in boosting testosterone compared to the standard mix of both isomers. Additionally, enclomifene has a half-life of just 10 hours, but zuclomifene has a half-life of 30 days—therefore if the goal is to boost testosterone, taking regular clomifene may produce far longer-lasting pro-estrogenic effects than pro-androgenic effects.


title: Clomifene

text: Clomifene has been used in the treatment of gynecomastia. It has been found to be useful in the treatment of some cases of gynecomastia but it is not as effective as tamoxifen or raloxifene for this indication. It has shown variable results for gynecomastia (probably because the zuclomifene isomer is estrogenic), and hence is not recommended for treatment of the condition. Pure enclomifene isomer is likely to be more effective than clomifene at treating gynecomastia, because of the lack of the zuclomifene isomer (as noted above).


title: Clomifene

text: Due to its long half-life, zuclomifene can be detected in urine for at least 261 days after discontinuation (261 days after discontinuation with a half-life of 30 days, there is still 0.24% of the peak level of zuclomifene being excreted, whereas with a half-life of 10 hours, enclomifene reaches the same 0.24% level in less than 4 days).


title: Clomifene

text: Because of its potential for boosting testosterone, clomifene is listed as banned for use by competitive sportsmen, both in and out of competition, by the World Anti-Doping Agency, absent an organic etiology of primary hypogonadism.


title: Clomifene

text: Contraindications include an allergy to the medication, pregnancy, prior liver problems, abnormal vaginal bleeding of unclear cause, ovarian cysts other than those due to polycystic ovarian syndrome, unmanaged adrenal or thyroid problems, and pituitary tumors.


title: Clomifene

text: The most common adverse drug reaction associated with the use of clomifene (>10% of people) is reversible ovarian enlargement.


title: Clomifene

text: Less common effects (1–10% of people) include visual symptoms (blurred vision, double vision, floaters, eye sensitivity to light, scotomata), headaches, vasomotor flushes (or hot flashes), light sensitivity and pupil constriction, abnormal uterine bleeding and/or abdominal discomfort.


title: Clomifene

text: Rare adverse events (<1% of people) include: high blood level of triglycerides, liver inflammation, reversible baldness and/or ovarian hyperstimulation syndrome.


title: Clomifene

text: Clomifene can lead to multiple ovulation, hence increasing the chance of twins (10% of births instead of ~1% in the general population) and triplets.


title: Clomifene

text: Rates of birth defects and miscarriages do not appear to change with the use of clomifene for fertility. Clomifene has been associated with liver abnormalities and a couple of cases of hepatotoxicity.


title: Clomifene

text: Some studies have suggested that clomifene if used for more than a year may increase the risk of ovarian cancer. This may only be the case in those who have never been and do not become pregnant. Subsequent studies have failed to support those findings.


title: Clomifene

text: Clomifene has been shown to be associated with an increased risk of malignant melanomas and thyroid cancer. Thyroid cancer risk was not associated with the number of pregnancies carried to viability.


title: Clomifene

text: Clomifene is a nonsteroidal triphenylethylene derivative that acts as a selective estrogen receptor modulator (SERM). It consists of a racemic mixture of zuclomifene (~38%) and enclomifene (~62%), each of which has unique pharmacologic properties. It is a mixed agonist and antagonist of the estrogen receptor (ER). Clomifene activates the ERα in the setting of low baseline estrogen levels and partially blocks the receptor in the context of high baseline estrogen levels. Conversely, it is an antagonist of the ERβ. Clomifene has antiestrogenic effects in the uterus. There is little clinical research on the influence of clomifene in many target tissues, such as lipids, the cardiovascular system, and the breasts. Positive effects of clomifene on bone have been observed. Clomifene has been found to decrease insulin-like growth factor 1 (IGF-1) levels in women.


title: Clomifene

text: Clomifene is a long-acting ER ligand, with a nuclear retention of greater than 48 hours. Clomifene is a prodrug being activated via similar metabolic pathways as the related triphenylethylene SERMs tamoxifen and toremifene. The affinity of clomifene for the ER relative to estradiol ranges from 0.1 to 12% in different studies, which is similar to the range for tamoxifen (0.06–16%). 4-Hydroxyclomifene, a major active metabolite of clomifene, and afimoxifene (4-hydroxytamoxifen), a major active metabolite of tamoxifen, show 89–251% and 41–246% of the affinity of estradiol for the ER in human MCF-7 breast cancer cells, respectively. The ER affinities of the isomers of 4-hydroxyclomifene were 285% for ("E")-4-hydroxyclomifene and 16% for ("Z")-4-hydroxyclomifene relative to estradiol. 4-Hydroxy-"N"-desmethylclomifene has similar affinity to 4-hydroxyclomifene for the ER. In one study, the affinities of clomifene and its metabolites for the ERα were ~100 nM for clomifene, ~2.4 nM for 4-hydroxyclomifene, ~125 nM for "N"-desmethylclomifene, and ~1.4 nM for 4-hydroxy-"N"-desmethylclomifene.


title: Clomifene

text: Even though clomifene has some estrogenic effect, the antiestrogenic property is believed to be the primary source for stimulating ovulation. Clomifene appears to act mostly in the hypothalamus where it depletes hypothalamic ERs and blocks the negative feedback effect of circulating endogenous estradiol, which in turn results in an increase in hypothalamic gonadotropin-releasing hormone (GnRH) pulse frequency and circulating concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).


title: Clomifene

text: In normal physiologic female hormonal cycling, at 7 days past ovulation, high levels of estrogen and progesterone produced from the corpus luteum inhibit GnRH, FSH, and LH at the hypothalamus and anterior pituitary. If fertilization does not occur in the post-ovulation period the corpus luteum disintegrates due to a lack of human chorionic gonadotropin (hCG). This would normally be produced by the embryo in the effort of maintaining progesterone and estrogen levels during pregnancy.


title: Clomifene

text: Therapeutically, clomifene is given early in the menstrual cycle. It is typically prescribed beginning on day 3 and continuing for five days. By that time, FSH levels are rising steadily, causing the development of a few follicles. Follicles, in turn, produce the estrogen, which circulates in serum. In the presence of clomifene, the body perceives a low level of estrogen, similar to day 22 in the previous cycle. Since estrogen can no longer effectively exert negative feedback on the hypothalamus, GnRH secretion becomes more rapidly pulsatile, which results in increased pituitary gonadotropin release. (More rapid, lower amplitude pulses of GnRH lead to increased LH and FSH secretion, while more irregular, larger amplitude pulses of GnRH leads to a decrease in the ratio of LH to FSH.) Increased FSH levels cause the growth of more ovarian follicles, and subsequently rupture of follicles resulting in ovulation. Ovulation occurs most often 6 to 7 days after a course of clomifene.


title: Clomifene

text: In normal men, 50 mg/day clomifene for 8 months has been found to increase testosterone levels by around 870 ng/dL in younger men and by around 490 ng/dL in elderly men. Estradiol levels increased by 62 pg/mL in younger men and by 40 pg/mL in elderly men. These findings suggest that the progonadotropic effects of clomifene are stronger in younger men than in older men. In men with hypogonadism, clomifene has been found to increase testosterone levels by 293 to 362 ng/dL and estradiol levels by 5.5 to 13 pg/mL. In a large clinical study of men with low testosterone levels (<400 ng/dL), 25 mg/day clomifene increased testosterone levels from 309 ng/dL to 642 ng/dL after 3 months of therapy. No significant changes in HDL cholesterol, triglycerides, fasting glucose, or prolactin levels were observed, although total cholesterol levels decreased significantly.


title: Clomifene

text: Clomifene is an inhibitor of the conversion of desmosterol into cholesterol by the enzyme 24-dehydrocholesterol reductase. Concerns about possible induction of desmosterolosis and associated symptoms such as cataracts and ichthyosis with extended exposure precluded the use of clomifene in the treatment of breast cancer. Continuous use of clomifene has been found to increase desmosterol levels by 10% and continuous high doses of clomifene (200 mg/day) have been reported to produce visual disturbances.


title: Clomifene

text: Clomifene produces "N"-desmethylclomifene, clomifenoxide (clomifene "N"-oxide), 4-hydroxyclomifene, and 4-hydroxy-"N"-desmethylclomifene as metabolites. Clomifene is a prodrug most importantly of 4-hydroxyclomifene and 4-hydroxy-"N"-desmethylclomifene, which are the most active of its metabolites. In one study, the peak levels after a single 50 mg dose of clomifene were 20.37 nmol/L for clomifene, 0.95 nmol/L for 4-hydroxyclomifene, and 1.15 nmol/L for 4-hydroxy-"N"-desmethylclomifene.


title: Clomifene

text: Clomifene has an onset of action of 5 to 10 days following course of treatment and an elimination half-life about 5 days. In one study, after a single 50 mg dose of clomifene, the half-life of clomifene was 128 hours (5.3 days), of 4-hydroxyclomifene was 13 hours, and of 4-hydroxy-"N"-desmethylclomifene was 15 hours. Individuals with the CYP2D6*10 allele showed longer half-lives for 4-hydroxyclomifene and 4-hydroxy-"N"-desmethylclomifene.


title: Clomifene

text: Most clomifene metabolism occurs in the liver, where it undergoes enterohepatic recirculation. Clomifene and its metabolites are excreted primarily through feces (42%), and excretion can occur up to 6 weeks after discontinuation.


title: Clomifene

text: Clomifene is a triphenylethylene derivative. It is a mixture of two geometric isomers, enclomifene ("(E)"-clomifene) and zuclomifene ("(Z)"-clomifene). These two isomers have been found to contribute to the mixed estrogenic and antiestrogenic properties of clomifene.


title: Clomifene

text: A team at William S. Merrell Chemical Company led by Frank Palopoli synthesized clomifene in 1956; after its biological activity was confirmed a patent was filed and issued in November 1959. Scientists at Merrell had previously synthesized chlorotrianisene and ethamoxytriphetol. Clomifene was studied in the treatment of advanced breast cancer during the period of 1964 to 1974 and was found to be effective but was abandoned due to concerns about desmosterolosis with extended use. Short-term use (e.g. days to months) did not raise the same concerns and clomifene continued to be studied for other indications.


title: Clomifene

text: Clinical studies were conducted under an Investigational New Drug Application; clomifene was third drug for which an IND had been filed under the 1962 Kefauver Harris Amendment to the Federal Food, Drug, and Cosmetic Act that had been passed in response to the thalidomide tragedy. It was approved for marketing in 1967 under the brand name Clomid. It was first used to treat cases of oligomenorrhea but was expanded to include treatment of anovulation when women undergoing treatment had higher than expected rates of pregnancy.


title: Clomifene

text: The drug is widely considered to have been a revolution in the treatment of female infertility, the beginning of the modern era of assisted reproductive technology, and the beginning of what in the words of Eli Y. Adashi, was "the onset of the US multiple births epidemic".


title: Clomifene

text: The company was acquired by Dow Chemical in 1980, and in 1989 Dow Chemical acquired 67 percent interest of Marion Laboratories, which was renamed Marion Merrell Dow. In 1995 Hoechst AG acquired the pharmaceutical business of Marion Merrell Dow. Hoechst in turn became part of Aventis in 1999, and subsequently a part of Sanofi. It became the most widely prescribed drug for ovulation induction to reverse anovulation or oligoovulation.


title: Clomifene

text: Clomifene is marketed under many brand names worldwide, including Beclom, Bemot, Biogen, Blesifen, Chloramiphene, Clofert, Clomene, ClomHEXAL, Clomi, Clomid, Clomidac, Clomifen, Clomifencitrat, Clomifene, Clomifène, Clomifene citrate, Clomifeni citras, Clomifeno, Clomifert, Clomihexal, Clomiphen, Clomiphene, Clomiphene Citrate, Cloninn, Clostil, Clostilbegyt, Clovertil, Clovul, Dipthen, Dufine, Duinum, Fensipros, Fertab, Fertec, Fertex, Ferticlo, Fertil, Fertilan, Fertilphen, Fertin, Fertomid, Ferton, Fertotab, Fertyl, Fetrop, Folistim, Genoclom, Genozym, Hete, I-Clom, Ikaclomin, Klofit, Klomen, Klomifen, Lomifen, MER 41, Milophene, Ofertil, Omifin, Ova-mit, Ovamit, Ovinum, Ovipreg, Ovofar, Ovuclon, Ovulet, Pergotime, Pinfetil, Profertil, Prolifen, Provula, Reomen, Serofene, Serophene, Serpafar, Serpafar, Surole, Tocofeno, and Zimaquin.


title: Clomifene

text: Clomifene is included on the World Anti-Doping Agency list of illegal doping agents in sport. It is listed because it is an "anti-estrogenic substance".


title: Clomifene

text: Clomifene has been used almost exclusively for ovulation induction in premenopausal women, and has been studied very limitedly in postmenopausal women.


title: Clomifene

text: Clomifene was studied for treatment and prevention of breast cancer, but issues with toxicity led to abandonment of this indication, as did the discovery of tamoxifen. Like the structurally related drug triparanol, clomifene is known to inhibit the enzyme 24-dehydrocholesterol reductase and increase circulating desmosterol levels, making it unfavorable for extended use in breast cancer due to risk of side effects like irreversible cataracts.


title: Sriya Reddy

text: Sriya Reddy (born 28 November 1983) is an Indian actress who mainly appears in Tamil language films and was also an anchor and VJ. Born to former Indian test cricketer Bharath Reddy, Sriya worked as successful VJ at SS Music before pursuing an acting career as well. Following her debut in "Samurai" (2002), she appeared in nearly a dozen Tamil, Telugu and Malayalam films, with "Black" (2004), "Thimiru" (2006) and "Kanchivaram" (2008) probably being her best known projects.


title: Sriya Reddy

text: Sriya was born to Bharath Reddy, an Indian cricketer. She did her schooling at Good Shepherd School and went on to study at Ethiraj College Chennai. When she was a child, cricketers Ravi Shastri and Sandeep Patil visited their home and complimented her good voice. During school, she received modelling offers, but had to decline them, since her father wanted her to finish her education first. When she was offered an audition for the leading music channel Southern Spice Music, she was able to convince her father that she would both study and be a VJ.