Archduchess Maria Anna of Austria (1738–1789)

Life.

Early life.

Archduchess Maria Anna (known as "Marianna") was born on 6 October 1738 at the Hofburg Palace in Vienna, the center of the vastly powerful Habsburg Monarchy. As the second but eldest surviving daughter of Maria Theresa, Queen of Hungary and Bohemia, and Francis I, Holy Roman Emperor, she was heiress presumptive of the hereditary lands of the Austrian Habsburgs between 1740 and 1741, until her younger brother Joseph (later to be the Holy Roman Emperor Joseph II) was born.  Her mother gave her the customary education of the princely courts at that time. Maria Anna's musical talents were highly encouraged, but not her humanities talents. Maria Anna was the child least respected and loved by Maria Theresa—her younger brother Joseph and sisters Maria Elisabeth and Marie Christine always received the attention and care of the Empress: Joseph because he was the male heir, Liesl because she was considered the most beautiful of the daughters, and Mimi because she was the undisputed favorite child of her mother.

Reign of Maria Theresa.

Maria Anna was highly intelligent but physically disabled. She suffered from bad health, worsened by the drafty and cold rooms of the Hofburg Palace. In 1757 she contracted pneumonia and almost died, the last rites being called for her. Although she survived, her breathing capacity was permanently damaged, and she also developed a fusion of her spine which caused her to have a lump on her back. After that time, she began to have a close relationship with her father, and reportedly became Francis I's favourite child. She shared his interest in science and conducted experiments in chemistry and physics. Despite being disabled, Maria Anna often played important roles in major events of state, including acting as sponsor at the christening of her youngest sister Marie Antoinette.  In July 1765 the whole Imperial family traveled to Innsbruck for the wedding of the second-oldest son, Leopold. They halted in Klagenfurt, where Maria Anna visited the small monastery that belonged to the Order of Saint Elisabeth, established there in 1710. The encounter with the sisters was to be a turning point in Maria Anna's life. Thea Leitner explains that the Archduchess became enthusiastic for the monastic life because the nuns didn't care about appearances and Maria Anna always lived with the fear of being ridiculed because of her hump.  The death of Emperor Francis I on 18 August 1765 was a devastating blow for Maria Anna. Because her mother was unable to find a royal husband for her, in 1766 Maria Anna was made Abbess of the Imperial and Royal Convent for Noble Ladies ("Frauenstift") in Prague with the promise of 80,000 florins per year. Despite the opposition of her mother, she decided to give up the Prague position and became an abbess in Klagenfurt with a smaller provision. A palace for her was built by Nicolò Pacassi near the monastery as her residence, the construction of which was completed in 1771.  To the abbess of the convent, she wrote:  During the time prior to her final move to Klagenfurt, Maria Anna completed her father's coin collection (which later became part of the Vienna Museum of Natural History) with the help of her mentor Ignaz von Born, and established her own mineral and insect collection. She financed social projects, archaeological exhumations, artists and scientists.  Maria Anna also wrote a book about her mother's politics. Her watercolors and drawings were praised in the professional world. Maria Anna was made an honorary member of the Academy of Fine Arts Vienna in 1767 and elected member of the Accademia di Belle Arti di Firenze in 1769.  Despite her talents and intelligence, Maria Anna was disliked by high society because her scientific interests were considered unsuitable for her gender, but she was appreciated by the scientific and art world.

Reign of Joseph.

Empress Maria Theresa died on 29 November 1780, and four months later, Maria Anna moved permanently to Klagenfurt. She quickly developed a deep friendship with Xaveria Gasser, Abbess of the convent. Thanks to the generous financial support of the Archduchess the monastery hospital could soon be extended, and her own personal physician supervised the patients of the hospital. She also provided welfare assistance in the municipality of Klagenfurt.  Her friends were nuns, artists, scientists, and nobles, including the Carinthian iron industrialist Maximilian Thaddäus von Egger. Some of them belonged to the Freemasons. In 1783, the Klagenfurt Masonic Lodge was founded with a dedication "to charitable Marianna" ("Zur wohltätigen Marianna") as she was called. Maria Anna devoted herself in Klagenfurt to her scientific interests. She discovered her love for archeology: she donated 30,000 florins for excavations at Zollfeld and also took part in the excavations herself.  Close to her younger sister Maria Elisabeth, the two lived together in the same convents till their deaths. While her youngest sister, Marie Antoinette, was traveling on her way to Versailles in 1770, she stayed at Klagenfurt for one night.  From the winter of 1788 Maria Anna's health deteriorated further. Her shortness of breath became worse and she could hardly move without a wheelchair. She died on 19 November 1789 in the presence of her closest friends. Reportedly, her last words were:  Maria Anna left her entire inheritance (amounting to more than 150,000 guilders) to the monastery of Klagenfurt. Her brother, Emperor Joseph II, deducted the inheritance tax from the income. Her palace is now home to the Prince Bishop's residence, in the "Mariannengasse".

Archduchess Maria Anna of Austria (Maria Anna Josepha Antonia; 6 October 1738 – 19 November 1789) was the second child of Francis I, Holy Roman Emperor, and Maria Theresa, Queen of Hungary and Bohemia. As a child, and for a time the eldest surviving child, she was heiress presumptive, but she suffered from ill health and physical disability, and did not marry. In 1766 she became abbess of the "Frauenstift" in Prague. Soon thereafter she moved to Klagenfurt and remained there for the rest of her life. Her palace in Klagenfurt, the "Mariannengasse", now houses the Episcopal Palace.


Anatomy and appearance.

Blue sharks are light-bodied with long pectoral fins. Like many other sharks, blue sharks are countershaded: the top of the body is deep blue, lighter on the sides, and the underside is white. The male blue shark commonly grows to at maturity, whereas the larger females commonly grow to at maturity. Large specimens can grow to long. Occasionally, an outsized blue shark is reported, with one widely printed claim of a length of, but no shark even approaching this size has been scientifically documented. The blue shark is fairly elongated and slender in build and typically weighs from in males and from in large females. Occasionally, a female in excess of will weigh over. The heaviest reported weight for the species was. The blue shark is also ectothermic and it has a unique sense of smell.

Reproduction.

They are viviparous, with a yolk-sac placenta, delivering four to 135 pups per litter. The gestation period is between nine and 12 months. Females mature at five to six years of age and males at four to five. Courtship is believed to involve biting by the male, as mature specimens can be accurately sexed according to the presence or absence of bite scarring. Female blue sharks have adapted to the rigorous mating ritual by developing skin three times as thick as male skin.

Ecology.

Range and habitat.

The blue shark is an oceanic and epipelagic shark found worldwide in deep temperate and tropical waters from the surface to about. In temperate seas it may approach shore, where it can be observed by divers; while in tropical waters, it inhabits greater depths. It lives as far north as Norway and as far south as Chile. Blue sharks are found off the coasts of every continent, except Antarctica. Its greatest Pacific concentrations occur between 20° and 50° North, but with strong seasonal fluctuations. In the tropics, it spreads evenly between 20° N and 20° S. It prefers water temperatures between, but can be seen in water ranging from. Records from the Atlantic show a regular clockwise migration within the prevailing currents.

Feeding.

Squid are important prey for blue sharks, but their diet includes other invertebrates, such as cuttlefish and pelagic octopuses, as well as lobster, shrimp, crab, a large number of bony fishes, small sharks, mammalian carrion and occasional sea birds. Whale and porpoise blubber and meat have been retrieved from the stomachs of captured specimens and they are known to take cod from trawl nets. Sharks have been observed and documented working together as a "pack" to herd prey into a concentrated group from which they can easily feed. Blue sharks may eat tuna, which have been observed taking advantage of the herding behaviour to opportunistically feed on escaping prey. The observed herding behaviour was undisturbed by different species of shark in the vicinity that normally would pursue the common prey. The blue shark can swim at fast speeds, allowing it to catch up with prey easily. Its triangular teeth allow it to easily catch hold of slippery prey.

Predators.

Young and smaller individuals may be eaten by larger sharks, such as the great white shark and the tiger shark. Killer whales have been reported to hunt blue sharks. This shark may host several species of parasites. For example, the blue shark is the definitive host of the tetraphyllidean tapeworm, "Pelichnibothrium speciosum" ("Prionacestus bipartitus"). It becomes infected by eating intermediate hosts, probably opah ("Lampris guttatus") and/or longnose lancetfish ("Alepisaurus ferox").  Northern elephant seals ("Mirounga angustirostris") have been observed to feed on blue sharks.

Relationship to humans.

It is estimated that 10 to 20 million of these sharks are killed each year as a result of fishing. The meat is edible, but not widely sought after; it is consumed fresh, dried, smoked and salted and diverted for fishmeal. There is a report of high concentration of heavy metals (mercury and lead) in the edible flesh. The skin is used for leather, the fins for shark-fin soup and the liver for oil. Blue sharks are occasionally sought as game fish for their beauty and speed.  Blue sharks rarely bite humans. From 1580 up until 2013, the blue shark was implicated in only 13 biting incidents, four of which ended fatally.

In captivity.

Blue sharks, like most pelagic sharks, tend to fare poorly in captivity. The first attempt of keeping blue sharks in captivity was at Sea World San Diego in 1968, and since then a small number of other public aquariums in North America, Europe and Asia have attempted it. Most of these were in captivity for about three months or less, and some of them were released back to the wild afterwards. The record time for blue sharks in captivity is 246 and 224 days for two individuals at Tokyo Sea Life Park, 210 days for an individual at New Jersey Aquarium, and 194 days for one at Lisbon Oceanarium.  Blue sharks are relatively easy to feed in captivity, and the three primary issues appear to be transport, predation by larger sharks and trouble avoiding smooth surfaces in tanks. Small blue sharks, up to long, are relatively easy to transport to aquariums, but it is much more complicated to transport larger individuals. However, this typical small size when introduced to aquariums means that they are highly vulnerable to predation by other sharks that are often kept, such as bull, grey reef, sandbar and sand tiger sharks. For example, several blue sharks kept at Sea World San Diego initially did fairly well, but were eaten when bull sharks were added to their exhibit. Attempts of keeping blue sharks in tanks of various sizes, shapes and depths have shown that they have trouble avoiding walls, aquarium windows and other smooth surfaces, eventually leading to abrasions to the fins or snout, which may result in serious infections. To keep blue sharks, it is therefore necessary with tanks that allow for relatively long, optimum swimming paths where potential contact with smooth surfaces is kept at a minimum. It has been suggested that prominent rockwork may be easier to avoid for blue sharks than smooth surfaces, as has been shown in captive tiger sharks.

Conservation status.

In June 2018 the New Zealand Department of Conservation classified the blue shark as "Not Threatened" with the qualifier "Secure Overseas" under the New Zealand Threat Classification System. The species is listed as Near Threatened by the IUCN.

The blue shark ("Prionace glauca") is a species of requiem shark, in the family Carcharhinidae, that inhabits deep waters in the world's temperate and tropical oceans. Averaging around and preferring cooler waters, the blue shark migrates long distances, such as from New England to South America. It is listed as Near Threatened by the IUCN.


Types.

T3.

The design of the T3 had to meet difficult specifications. The cars needed to have the same capacity as its predecessor (the Tatra T2), but be easier to build. Some of the things that were done in order to meet this goal were making the walls thinner, and fitting the cars with laminate seats instead of cushioned leatherette seats such as the T2 used. The T3 was delivered to all tramway companies in the former Czechoslovakia. It was most numerous in Prague, where over 1,000 vehicles were delivered. The T3 still forms (mostly in various modernised versions) the backbone of the Czech tram fleet.

T3SU.

As with the T2SU, the first T3SU was delivered with the modification of removing the middle door and replacing it with seats. Later cars, however, were delivered with the third door in place. Again, the vehicles had a closed operator's compartment and were adapted for the harsh climate. Altogether 11,368 T3SU were delivered, making it the largest production of a single type of streetcar worldwide. But because so many of one type were made, their replacement by more modern cars was slow.  The T3SU was delivered from 1963, first to Moscow and later to 33 further Soviet cities.

T3SUCS.

Originally, the production of the T3 was stopped in 1976 and focus shifted to newer vehicles. The Slovak city Košice, however, ordered two motor coaches as an exception. The production of the replacement type KT8D5 was slated to begin in 1985, but this model was by then obsolete. Further production of the T3 would have been too expensive, so instead vehicles of the type T3SU were re-imported and adapted. The closed operator's cab was maintained, the vehicles had all three doors in place, and differed from the original T3 only in a few details.

T3SU Evolution.

Over time, the T3SU has had minor changes in both exterior appearance and interior design.  Exterior details:  Interior:

T3D.

In East Germany the first three T3D cars started operation in 1964 and the city of Dresden got its first delivery in 1965. The cars were used in part due to their width of. They operated as single cars or as multiple units (motor+motor, motor+motor+trailer) and/or as mini trams (motor+trailer). The use of trailer cars was due to the use of original Czech T3 electrical equipment, which had enough power to support trailer cars. However, due to reduced available power, the maximum speed of the streetcar reached only 55 km/h instead of the usual.  Only German and Yugoslav networks had trailer cars. The car was designated as B3D and had the same body as the T3D. Today, only Chemnitz uses T3s in full service as the T3D-M (modified).

T3YU.

From 1967 onwards, vehicles supplied to Yugoslavia differed from the standard type T3 by having different pantographs and trucks. In addition, trailer cars were used, as in East Germany. Uncommonly, the network used narrow-profile vehicles, two of which could be found in Czechoslovakia and one in the Soviet Union.

T3R.

At the end of the 1960s, Romania ordered RA cars as part of an agreement in the Comecon. The first vehicles came in 1970 to the city of Galați and had different electrical equipment from the Czechoslovak vehicles, to use the network's 750 V DC voltage. Since the carbodies were built too wide for use elsewhere, they remained in Galați. Only 50 units were delivered. Romania then opted for the narrower Tatra T4, which had more success, being still used in Bucharest as of 2019.  A few more of the same type were manufactured in 1997.

T3RF.

Four Tatra T3RF were the very last T3 trams built. They were made for Samara and Izhevsk, but only Samara bought them. In 2002 the two others were sold to Brno and modernized.

Modernized Tatra-T3 trams.

In most Czech cities and in some others such as Bratislava, Moscow, Riga, and Odessa, Tatra-T3 trams became very common. As a result, service and maintenance workers became very experienced at servicing them. This was one reason for modifying existing trams rather than replacing them with newer stock (the other being cost).  Modernization normally includes:  More radical modernization includes insertion of a low-floor section (e.g. Tatra K3R-NT).

Production.

14,113 trams were produced and delivered to:  Note: This is the list of first owners. Stock may have later been resold to other cities not on this list.

The T3 is a type of Czech tramcar produced by ČKD Tatra. A late-2000s study conducted on the Prague tram system has shown 98.9% reliability, the best of the Prague tram system fleet. During its period of production, between 1960 and 1999, 13,991 powered units and 122 unpowered trailers were sold worldwide.


Biology.

The larva of this species first feeds on "Sanguisorba officinalis" (great burnet), then moves onto ant nests and is a predator of the ant brood. "Myrmica rubra" and "Myrmica scabrinodis" have been reported as frequent host ant species. A recent microhabitat preference study indicates that grazing is necessary for maintaining the present distribution and abundance of these butterflies.

Description from Seitz.

"L. euphemus" Hbn. (= diomedes Rott.) (83 a), Male above almost entirely blue, but not shining; the margins, the discocellular spot of the forewing and commonly some small spots on the disc black; female much blacker, often a little paler on the disc, this lighter area bearing rows of black spots. Underside with very numerous ocelli, which are rarely as large and conspicuous as in our figure of the underside. The species is at once distinguished from the very similar "arion" by the underside not bearing an ocellus in the cell proximally to the discocellular spot. Throughout Europe (with the exception of England) and the adjacent districts of Asia, from North Germany and Russia to Italy, and from Paris to Dauria. — Near the North- Western boundary there occur especially small individuals (of the size of "icarus"), which have but few ocelli; these are ab. "paula" Schultz. In ab. "obsoleta" Gillm. the ocelli of the hindwing are entirely absent or almost, while in ab. "striata" Gillm. they are modified into streaks. — "obscurata" Stgr. (83 b) is a strongly darkened form from Central Asia (also already in the Ural) — "euphemia" Stgr. (83 b) is much larger than European specimens, with a broad block border which sharply contrasts with the light blue; from Amurland. North China and Corea. — "kazamoto" Druce (83 b), from Japan, is above uniformly black-brown above in both sexes, without any trace of blue, and the underside is more strongly ocellate. — Egg semiglobular with the top sunk in, greenish white, laid on "Sanguisorba" (usually on the inflorescence). The young larva purplish brown with black head and pale segmental incissions; it bores into the heads of the plant and lives later on in the seed-pods ; it hibernates. Pupa on the ground, under stones, clods of earth, and the dead leaves of the food-plant. The butterflies are sporadic, their localities being widely dispersed. They fly in damp meadows where "Sanguisorba" grows, being here usually very abundant. They settle almost exclusively on Sanguisorba: when disturbed they fly mostly only as far as the nearest cluster of that plant, where they settle on a flower with the wings always closed, their flight being rather slow and flapping. In July and August.

Subspecies.

There are six subspecies.

The scarce large blue ("Phengaris teleius") is a species of butterfly in the family Lycaenidae. It is found in Austria, Slovenia, Croatia, the Czech Republic, France, Georgia, Germany, Hungary, Italy, Japan, Kazakhstan, Mongolia, the Netherlands, Poland, Romania, Russia, northern Serbia, Spain, Switzerland, and Ukraine and East across the Palearctic to Japan. The species was first described by Johann Andreas Benignus Bergsträsser in 1779.


Synopsis.

Original "for Muggles" version.

"Fantastic Beasts" purports to be a reproduction of a textbook owned by Harry Potter and written by magizoologist Newt Scamander, a character in the fictional "Harry Potter" series. In the series, magizoology is the study of magical creatures.  Albus Dumbledore, headmaster of Hogwarts, provides the foreword and explains the purpose of the special edition of this book (the Comic Relief charity). At the end, he assures muggle readers, "The amusing creatures described hereafter are fictional and cannot hurt you." He repeats the Hogwarts motto: "Draco dormiens nunquam titillandus", Latin for "Never tickle a sleeping dragon".  "Fantastic Beasts and Where to Find Them" contains the history of magizoology and describes 85 magical species found around the world. Scamander says that he collected most of the information found in the book through observations made over years of travel across five continents. He notes that the first edition was commissioned in 1918 by Augustus Worme of Obscurus Books. However, it was not published until 1927. It is now in its fifty-second edition.  In the Harry Potter universe, the book is a required textbook for first-year Hogwarts students, having been an approved textbook since its first publication. In his foreword to the book, Albus Dumbledore notes that it serves as an excellent reference for wizarding households in addition to its use at Hogwarts.  The book features doodles and comments added by Ron Weasley. The comments would appear to have been written around the time of the fourth book, "Harry Potter and the Goblet of Fire". These doodles add some extra information for fans of the series (for example the "Acromantula" entry has a comment confirming that Hogwarts is located in Scotland) along with comic relief (such as Ron stating "you're not kidding" when talking about the Hungarian Horntail being the most fearsome dragon of all, a reference to Harry's encounter with one in the fourth book).  The cover design of the first edition of the book features apparent claw marks from an unidentified animal.

2017 "for Wizards" version.

This edition features six new creatures: the hidebehind, the hodag, the horned serpent, the snallygaster, the thunderbird, and the wampus cat, in addition to the original 75, and the illustrations are replaced. Newt Scamander, in the foreword, explains the reason the six new creatures were not previously included is because MACUSA president Seraphina Picquery requested the more important American creatures not be mentioned to deter wizarding sightseers at a time when the US wizarding community were subject to greater persecution than their European counterparts, and after Scamander had contributed to a serious breach of the International Statute of Secrecy in New York.

Role in the "Harry Potter" series.

The book's fictional author, Newt Scamander, does not appear in the main "Harry Potter" book series though his name is seen on the Marauder's Map in Harry Potter and the Prisoner of Azkaban. He is the central character of the "Fantastic Beasts" film series, in which he is played by Eddie Redmayne.

Featured beasts.

The following mythological beasts are listed in the book:

Reception.

Jeff Jensen of "Entertainment Weekly" graded the book with an "A" and wrote "With its richly detailed history lessons and witty debate parsing the differences between "being" and "beast", plus a compendium of 85 magical creatures that's chockablock with Rowling's trademark wordplay ("Glumbumble" is a standout), "Beasts" adds a vital new dimension to the Potter mythology."

Adaptations.

Audiobook.

The 2017 version of the book was recorded as an unabridged audiobook in 2017. The audiobook is read by Eddie Redmayne in the character of Newt Scamander.

Film adaptations.

"Fantastic Beasts and Where to Find Them" is a British-American fantasy film inspired by the book of the same name by J. K. Rowling. An extension of the wizarding world from the "Harry Potter" film series and directed by David Yates, the film stars Eddie Redmayne, Katherine Waterston, Alison Sudol, Dan Fogler, Samantha Morton, Ezra Miller, Colin Farrell, Carmen Ejogo, Faith Wood-Blagrove, Jenn Murray, Jon Voight and Ron Perlman. The first movie is set to be followed by four more. Principal photography commenced on 17 August 2015, at Warner Bros. Studios, Leavesden. "Fantastic Beasts and Where to Find Them" was released in the United Kingdom and the United States on 18 November 2016.  A was released on 16 November 2018. The third movie is scheduled to be released in November 2021.

Fantastic Beasts and Where to Find Them (often referred to as simply Fantastic Beasts) is a 2001 guide book written by British author J. K. Rowling (under the pen name of the fictitious author Newt Scamander) about the magical creatures in the "Harry Potter" universe. The original version, illustrated by the author herself, purports to be Harry Potter's copy of the textbook of the same name mentioned in "Harry Potter and the Philosopher's Stone" (or "Harry Potter and the Sorcerer's Stone" in the US), the first novel of the "Harry Potter" series. It includes several notes inside it supposedly handwritten by Harry, Ron Weasley, and Hermione Granger, detailing their own experiences with some of the beasts described, and including in-jokes relating to the original series.


Description.

The tree starts bearing its first fruit when it is 10 to 15 years old; full production is attained when the tree is about 20 to 30 years old. It then produces nuts for up to 200 years.  The fruits resemble large plums and take 4 to 6 months to ripen. The average yield is 15 to 20 kilograms of fresh fruit per tree, with optimum yields up to 45 kilograms. Each kilogram of fruit gives approximately 400 grams of dry seeds.

Composition.

Shea butter fatty acid profiles.

Shea butter is composed of five principal fatty acids: palmitic, stearic, oleic, linoleic, and arachidic (see Table below). About 85 to 90% of the fatty acid composition is stearic and oleic acids. The relative proportion of these two fatty acids affects shea butter consistency. The stearic acid gives it a solid consistency, while the oleic acid influences how soft or hard the shea butter is, depending on ambient temperature.  The proportions of stearic and oleic acids in the shea kernels and butter differ across the distribution range of the species. Ugandan shea butter has consistently high oleic acid content, and is liquid at warm ambient temperatures. It fractionizes into liquid and solid phases, and is the source of liquid shea oil. The fatty acid proportion of West African shea butter is much more variable than Ugandan shea butter, with an oleic content of 37 to 55%. Variability can be high even locally, and a tree that produces hard butter can grow with one that produces soft butter.  Nuts are gathered from a wide area for local production, so shea butter consistency is determined by the average fatty acid profile of the population. Within West Africa, shea butter from the Mossi Plateau region of Burkina Faso has a higher average stearic acid content, and so is usually harder than shea butter from other West African regions.

Shea butter phenolics.

Phenolic compounds are known to have antioxidant properties. A recent study characterized and quantified the most important phenolic compounds in shea butter. This study identified 10 phenolic compounds, eight of which are catechins, a family of compounds being studied for their antioxidant properties. The phenolic profile is similar to that of green tea, and the total phenolic content of shea butter is comparable to virgin olive oil. Also, this study was performed on shea butter that had been extracted with hexane, and the authors note that traditional extraction methods may result in higher phenolic levels.  Furthermore, they note that the catechin content alone of shea kernels is higher than the total phenolic content of ripe olives. This study also found that the overall concentration and relative percentages of different phenolic content in shea kernels varied from region to region. The authors hypothesized that the overall concentration of phenols in shea kernels is linked to the level of environmental stress that the trees endure.

Distribution and habitat.

The shea tree grows naturally in the wild in the dry savannah belt of West and South from Senegal in the west to Sudan and South Sudan in the east, and onto the foothills of the Ethiopian highlands. It occurs in 19 countries across the African continent, namely Benin, Burkina Faso, Cameroon, Central African Republic, Chad, Ethiopia, Ghana, Guinea Bissau, Ivory Coast, Mali, Niger, Nigeria, Senegal, Sierra Leone, South Sudan, Sudan, Togo, Uganda, Democratic Republic of the Congo, and Guinea.  A testa found at the site of the medieval village of Saouga is evidence of shea butter production by the 14th century.

Uses.

Shea butter has many uses and may or may not be refined. In the West it is most commonly used as an emollient in cosmetics and is less commonly used in food. Throughout Africa it is used extensively for food, is a major source of dietary fat, and for medicinal purposes. In Ghana and Nigeria, shea butter is a major ingredient for making the African black soap. The edible protein-rich caterpillars of the moth "Cirina butyrospermi" which feed solely on its leaves are widely collected and eaten raw, dried or fried.

Etymology.

The common name is "shíyiri" or "shísu" (lit. "shea tree") in the Bambara language of Mali. This is the origin of the English word, whose primary pronunciation is (rhyming with "tea"), although the pronunciation (rhyming with "day") is common and is listed second in major dictionaries. The tree is called "ghariti" in the Wolof language of Senegal, which is the origin of the French name of the tree and the butter, "karité".  In Hausa language the tree is called Kade or Kadanya. Indeed, the shea tree is so indispensable in Mole-Dagbang culinary and ethno-botanical practices that the Northern Ghanaian city of Tamale etymologically derives its name from the more traditional Dagomba name 'Tama-yile' (meaning 'Home of Shea nuts').  The tree was formerly classified in the genus "Butyrospermum", meaning "butter seed". The species name "parkii" honors Scottish explorer Mungo Park, who learned of the tree while exploring Senegal. Park's Scottish origin is reflected in the English word shea, with a final -ea.

Vitellaria paradoxa (formerly "Butyrospermum parkii"), commonly known as shea tree, shi tree (), or vitellaria, is a tree of the family Sapotaceae. It is the only species in the genus Vitellaria, and is indigenous to Africa.


Early life.

Known to her family as Christa, she was born at Židlochovice Castle (Groß Seelowitz), near Brünn (now Brno), in Moravia, a daughter of Archduke Karl Ferdinand of Austria and his wife, Archduchess Elisabeth Franziska of Austria.  Her paternal grandparents were Archduke Charles of Austria and Princess Henriette Alexandrine of Nassau-Weilburg.  Various sources attributed good traits to Maria Christina before her marriage. One states she was "tall, fair, sensible, and well educated". She was Princess-Abbess of the Theresian Royal and Imperial Ladies Chapter of the Castle of Prague (1875-1879).

Marriage and issue.

Maria Christina married King Alfonso XII of Spain on 29 November 1879 at the Basilica of Atocha in Madrid, and became the mother of his only three legitimate children:  His previous wife was his first cousin, Mercedes of Orléans, who had died half a year after their marriage, leaving no issue. She lived a discreet life as queen. She was the first Germanic queen consort in half-a-century since Maria Josepha Amalia of Saxony, the third wife of Ferdinand VII.

Regency.

When the King died on 25 November 1885, Maria Christina was pregnant, so the throne was vacant, depending on whether Maria Christina's unborn child was a male or a female; a male would make that child king, while a female would place her elder daughter, Infanta María Mercedes, on the throne. During this period, Maria Christina ruled as regent until her child, a son, was born on 17 May 1886; he was King Alfonso XIII of Spain from birth. Maria Christina continued as regent until Alfonso XIII attained his majority in 1902; she is the "Her Majesty The Queen of Spain, The Queen Regent" named as concluding the Treaty of Paris (1898) with the United States of America, ending the Spanish–American War.  Her chief adviser and head of government was Práxedes Mateo Sagasta. Her rule is described as well-balanced and in accordance with respect for constitutional rights, and many political reforms were instated during her regency to prevent political conflicts and chaos. Her role was mostly ceremonial, and her purpose was to preserve the crown for her son until he became an adult.

Later life.

After her son's marriage in 1906, she lost her position as first lady at court. Nevertheless, Alfonso XIII continued to look to her on many occasions for advice.  In February 1929, after some weeks of heart disease, she died at the Royal Palace in Madrid and is buried at El Escorial. Sir Charles Petrie, Alfonso XIII's biographer, maintained that the Queen dowager's death had a disastrous effect on her son, and that the latter never recovered politically from the blow. Within little more than two years the monarchy had collapsed.

Honours.

She received the following awards:

Archduchess Maria Christina Henriette Desideria Felicitas Raineria of Austria, also known as Maria Christina Henrietta Désirée Félicité Rénière (21 July 1858 – 6 February 1929) was Queen of Spain as the second wife of King Alfonso XII. She was regent during the vacancy of the throne between her husband's death and her son's birth, and during the minority of their son, Alfonso XIII, between 1885 and 1902.


History.

The Gare de l'Est was opened in 1849 by the Compagnie du Chemin de Fer de Paris à Strasbourg (Paris–Strasbourg Railway Company) under the name "Strasbourg platform" ("Embarcadère de Strasbourg"); an official inauguration with President Louis Napoléon Bonaparte took place the next year. The platform corresponds today with the hall for main-line trains. Designed by architect François Duquesnay, it was renamed the "Gare de l'Est" in 1854, after the expansion of service to Mulhouse.  Renovations followed in 1885 and 1900, part of Haussmann's renovation of Paris. In 1931 it was doubled in size, with the new part of the station built symmetrically with the old part. This transformation changed the surrounding neighbourhood significantly. At the top of the west facade of the Gare de l'Est is a statue by the sculptor Philippe Joseph Henri Lemaire, representing the city of Strasbourg, while the east end of the station is crowned by a statue personifying Verdun, by Varenne. These two cities are important destinations serviced by Gare de l'Est. On 4 October 1883, the Gare de l'Est saw the first departure of the "Orient Express" for Istanbul.  The Gare de l'Est is the terminus of a strategic railway network extending towards the eastern part of France, and it saw large mobilizations of French troops, most notably in 1914, at the beginning of World War I. In the main-line train hall, a monumental painting by Albert Herter, "Le Départ des poilus, août 1914" dating from 1926, illustrates the departure of these soldiers for the Western front. The SNCF started LGV Est Européenne services from the Gare de l'Est on 10 June 2007, with TGV and Intercity-Express (ICE) services to Northeastern France, Luxembourg, Southern Germany and Switzerland. Trains are initially planned to run at 320 km/h (198 mph), with the potential to run at 350 km/h (217 mph), cutting travel times by up to 2 hours.

Train services.

The following services currently call at Paris-Est:

The Gare de l'Est (pronounced, "Station of the East"), officially Paris-Est, is one of the six large SNCF termini in Paris. It is in the 10th arrondissement, not far from the Gare du Nord, facing the Boulevard de Strasbourg, part of the north-south axis of Paris created by Georges-Eugène Haussmann. It is one of the largest and the oldest railway stations in Paris, the western terminus of the Paris–Strasbourg railway and the Paris–Mulhouse railway which then proceeds to Basel, Switzerland.


History.

1840 station.

The Gare D’Austerlitz was the main station in Paris for the Paris-Orléans (PO) company and was originally called the Gare d'Orléans station. The station is near the Quai d'Austerlitz, and the bridge that gives it its name. These were named after the Czech town once known as Austerlitz (today Slavkov u Brna). Napoleon I defeated the superior numbers of the Third Coalition there on 2 December 1805 at the Battle of Austerlitz.  Built from 1838, the first platform was built slightly back from the current location of the station by the architect Félix-Emmanuel Callet and began service on 20 September 1840, on the occasion of the opening of the Paris-Corbeil line, which was extended to Orléans in May 1843. Part of the rue Poliveau was cut by this construction, and another part, located near the Seine, took the name of rue Jouffroy.  The first expansion took place in 1846.

1867 station.

Demolished, the station was rebuilt, from 1862 to 1869, by Pierre-Louis Renaud (1819-1897), chief architect of the Paris-Orléans company. It included a large hall made from iron, wide and long (the second largest in France after Bordeaux), designed by Ferdinand Mathieu and carried out by the construction workshops of Schneider & Co at Le Creusot and Chalon-sur-Saone. This vast space was also used as a workshop for making gas balloons, during the Siege of Paris in 1870. Also built was the departure pavilion to the north, the perpendicular building of the restaurant buffet, the arrival pavilion to the south, as well as the Paris-Orléans railway administration building at the west end of the hall, on Place Valhubert, with a "Belle Époque" style façade. The administrative building was an extension of the iron hall, whose pediment was invisible from Place Valhubert. This arrangement, as well as the choice of side entrances, was unusual for a terminal station.

Evolution since 1900.

In 1900, the Paris-Orléans company extended its railway line towards the centre of the capital, with the Gare d'Orsay becoming the new head of line, when it entered service on 28 May on the occasion of the Exposition Universelle. The design was by architect Victor Laloux, and the construction by the contractor Léon Chagnaud. In 1906, the great hall of Gare d'Austerlitz was literally pierced through its width by the Metro 5 line by an extension of a viaduct crossing the Seine. An elevated station was located in the hall.  In 1910, during the great flood of the Seine, the station was flooded and rail traffic completely interrupted from 31 January to 9 February. During this period, the departure and arrival of the trains were terminated at Gare de Juvisy.  Since 1926, the Paris-Vierzon line was electrified to 1500 V, so no more steam engines entered Austerlitz. It was the first station in Paris to no longer receive a steam train.  In 1939, the Gare d'Orsay saw its function limited to suburban traffic, and the Gare d'Austerlitz once again became a terminus station for the main lines.  On 28 February 1997, part of the station were classified as historical monuments, especially its facades and glass roof.

Future.

A large refurbishment project of the Paris Austerlitz is currently under way. Four new platforms are being constructed and all the existing tracks are being refurbished. The interior will be rebuilt in order to handle TGV Sud-Est and TGV Atlantique services, partially transferred from the Gare de Lyon and Gare Montparnasse, both of which are at maximum capacity. All the work is planned to be completed by 2020, and will double the activity at the station.

Train services.

The following services currently call at Paris-Austerlitz:  Gare d'Austerlitz also hosts stations on the Paris Métro (lines 5 and 10, see Gare d'Austerlitz (Paris Métro)) and RER.

The Gare d'Austerlitz ("Austerlitz Station"), officially Paris-Austerlitz, is one of the six large terminus railway stations in Paris. It is on the left bank of the Seine in the southeastern part of the city, in the 13th arrondissement. It is the start of the Paris–Bordeaux railway; the line to Toulouse is connected to this line. Since the introduction of the TGV Atlantiqueusing Gare MontparnasseAusterlitz has lost most of its long-distance southwestern services. It is used by some 30 million passengers annually, about half the number passing through Montparnasse.


Signs and symptoms.

Agranulocytosis may be asymptomatic, or may clinically present with sudden fever, rigors and sore throat. Infection of any organ may be rapidly progressive (e.g., pneumonia, urinary tract infection). Sepsis may also progress rapidly.

Causes.

A large number of drugs have been associated with agranulocytosis, including antiepileptics (such as carbamazepine and valproate), antithyroid drugs (carbimazole, thiamazole, and propylthiouracil), antibiotics (penicillin, chloramphenicol and co-trimoxazole), H2 blockers (cimetidine, famotidine, nizatidine, ranitidine), ACE inhibitors (benazepril), cytotoxic drugs, gold, analgesics (aminophenazone, indomethacin, naproxen, phenylbutazone, metamizole), mebendazole, allopurinol, the antidepressants mianserin and mirtazapine, and some antipsychotics (the atypical antipsychotic clozapine in particular). Clozapine users in the United States, Australia, Canada, and the UK must be nationally registered for monitoring of low WBC and absolute neutrophil counts (ANC).  Although the reaction is generally idiosyncratic rather than proportional, experts recommend that patients using these drugs be told about the symptoms of agranulocytosis-related infection, such as a sore throat and a fever.  The Centers for Disease Control traced outbreaks of agranulocytosis among cocaine users, in the US and Canada between March 2008 and November 2009, to the presence of levamisole in the drug supply. The Drug Enforcement Administration reported that, as of February 2010, 71% of seized cocaine lots coming into the US contained levamisole as a cutting agent. Levamisole is an antihelminthic (i.e. deworming) drug used in animals. The reason for adding levamisole to cocaine is unknown, although it can be due to their similar melting points and solubilities.

Diagnosis.

The diagnosis is made after a complete blood count, a routine blood test. The absolute neutrophil count in this test will be below 500, and can reach 0 cells/mm3. Other kinds of blood cells are typically present in normal numbers.  To formally diagnose agranulocytosis, other pathologies with a similar presentation must be excluded, such as aplastic anemia, paroxysmal nocturnal hemoglobinuria, myelodysplasia and leukemias. This requires a bone marrow examination that shows normocellular (normal amounts and types of cells) blood marrow with underdeveloped promyelocytes. These underdeveloped promyelocytes, if fully matured, would have been the missing granulocytes.

Classification.

The term "agranulocytosis" derives from the Greek: "a", meaning without; granulocyte, a particular kind of white blood cell (containing granules in its cytoplasm); and "osis", meaning condition [esp. disorder]. Consequently, agranulocytosis is sometimes described as "no granulocytes", but a total absence is not required for diagnosis. However, "-osis" is commonly used in blood disorders to imply cell proliferation (such as in "leukocytosis"), while "-penia" to imply reduced cell numbers (as in "leukopenia"); for these reasons, granulopenia is a more etymologically consistent term, and as such, is sometimes preferred to "agranulocytosis" (which can be misinterpreted as "agranulocyt-osis", meaning proliferation of agranulocytes (i.e. lymphocytes and monocytes). Despite this, "agranulocytosis" remains the most widely used term for the condition.  The terms agranulocytosis, granulocytopenia and neutropenia are sometimes used interchangeably. Agranulocytosis implies a more severe deficiency than granulocytopenia. Neutropenia indicates a deficiency of neutrophils (the most common granulocyte cell) only.  To be precise, neutropenia is the term normally used to describe absolute neutrophil counts (ANCs) of less than 500 cells per microlitre, whereas agranulocytosis is reserved for cases with ANCs of less than 100 cells per microlitre.  The following terms can be used to specify the type of granulocyte referenced:  In a general sense the pathogenesis of neutropenia can be divided into two categories;

Treatment.

In patients that have no symptoms of infection, management consists of close monitoring with serial blood counts, withdrawal of the offending agent (e.g., medication), and general advice on the significance of fever.  Transfusion of granulocytes would have been a solution to the problem. However, granulocytes live only ~10 hours in the circulation (for days in spleen or other tissue), which gives a very short-lasting effect. In addition, there are many complications of such a procedure.

Agranulocytosis, also known as agranulosis or granulopenia, is an acute condition involving a severe and dangerous leukopenia (lowered white blood cell count), most commonly of neutrophils, and thus causing a neutropenia in the circulating blood. It is a severe lack of one major class of infection-fighting white blood cells. People with this condition are at very high risk of serious infections due to their suppressed immune system.


Life.

He was born in Bologna about 1050.  At the urging of Countess Matilda of Tuscany he began to devote himself to the study of jurisprudence, taking the Justinian code as a guide. After teaching jurisprudence for a short while in Rome he returned to Bologna, where he founded a new school of jurisprudence in 1084 or 1088, which would rival the law school of Ravenna.  Some jurisprudence had been taught at Bologna, before Irnerius founded his school, by Pepo and a few others, and a tradition of jurisprudence had developed at Pavia since the mid-ninth century. He introduced the custom of explaining the Roman law by means of glosses, which originally were meagre interlinear elucidations of the text. But since the glosses were often too extensive to be inserted between the lines of the text, he began to write them on the margin of the page, thus being the first to introduce the marginal glosses which afterwards came into general use. After the death of Pope Paschal II, he defended the rights of Emperor Henry V in the papal election and upheld the legality of the election of the imperial antipope Gregory VIII. After 1116 he appears to have held some office under the emperor. He died, perhaps during the reign of the emperor Lothair II, but certainly before 1140.

Teaching.

Irnerius taught along lines firmly established in the teaching of Scripture, by reading aloud a section of the civil law, which the students would copy, and add to the text his commentary and explanatory glosses. Thus he was the first of the glossators, whose explications of the law became an essential part of the legal curriculum.  The text of Justinian's "Pandects" used in Bologna, referred to as the "Littera Bononiensis", closely parallel to the "Littera Florentina", would be disseminated throughout Europe as students returned home from Bologna: there are versions of the Bolognese "Littera" with provenances in Paris, Padua, Leipzig and at the Vatican (Purpura 2001).

Works.

According to ancient opinion (which, however, has been much controverted), Irnerius was the author of the epitome of the "Novellae" of Justinian, called the "Authentica", arranged according to the titles of the Code. His "Formularium tabellionum" (a directory for notaries) and "Quaestiones" (a book of judicial decisions) are no longer extant.  The "Summa Codicis", attributed to Irnerius by Herman Fitting in his 1894 edition is now widely considered a later work of between 1130 and 1159, but remains the earliest known summa on Justinian's "Code"  Another important work, "Quaestiones de juris subtilitatibus", was generally ascribed to Irnerius until Hermann Kantorowicz published a manuscript from the British Museum.  Other juridical works and glosses that are ascribed to Irnerius are extant only in fragments, or their authorship is uncertain.

Reputation.

Irnerius was largely forgotten until his name was revived by German historians of the later 19th century and came to prominence with the celebrations marking the octocentennial of the University of Bologna. His name is also seen in manuscripts as Hirnerius, Hyrnerius, Iernerius, Gernerius, Garnerius, Guarnerius, Warnerius, Wernerius, Yrnerius. He called himself Wernerius when he signed documents.  Anders Winroth has questioned much of the received account of Irnerius' life as well as his importance to the history of Roman law in the Middle Ages.

Irnerius (c. 1050 – after 1125), sometimes referred to as "lucerna juris" ("lantern of the law"), was an Italian jurist, and founder of the School of Glossators and thus of the tradition of Medieval Roman Law.


Signs and symptoms.

The most common and obvious sign of retinoblastoma is an abnormal appearance of the retina as viewed through the pupil, the medical term for which is leukocoria, also known as amaurotic cat's eye reflex. Other signs and symptoms include deterioration of vision, a red and irritated eye with glaucoma, and faltering growth or delayed development. Some children with retinoblastoma can develop a squint, commonly referred to as "cross-eyed" or "wall-eyed" (strabismus). Retinoblastoma presents with advanced disease in developing countries and eye enlargement is a common finding.  Depending on the position of the tumors, they may be visible during a simple eye exam using an ophthalmoscope to look through the pupil. A positive diagnosis is usually made only with an examination under anesthetic (). A white eye reflection is not always a positive indication of retinoblastoma and can be caused by light being reflected badly or by other conditions such as Coats' disease.  The presence of the photographic fault red eye in only one eye and not in the other may be a sign of retinoblastoma. A clearer sign is "white eye" or "cat's eye" (leukocoria).

Cause.

Mutation of genes, found in chromosomes, can affect the way in which cells grow and develop within the body. Alterations in RB1 or MYCN can give rise to retinoblastoma.

RB1.

In children with the heritable genetic form of retinoblastoma, a mutation occurs in the "RB1" gene on chromosome 13." RB1" was the first tumor suppressor gene cloned. Although" RB1" interacts with over 100 cell proteins, its negative regulator effect on the cell cycle principally arises from binding and inactivation of the transcription factor "E2F", thus repressing the transcription of genes which are required for the S phase.  The defective "RB1 "gene can be inherited from either parent; in some children, however, the mutation occurs in the early stages of fetal development. The expression of the" RB1 "allele is autosomal dominant with 90% penetrance.  Inherited forms of retinoblastomas are more likely to be bilateral. In addition, inherited uni- or bilateral retinoblastomas may be associated with pineoblastoma and other malignant midline supratentorial primitive neuroectodermal tumors (PNETs) with a dismal outcome; retinoblastoma concurrent with a PNET is known as trilateral retinoblastoma. A recent meta-analysis has shown that survival of trilateral retinoblastoma has increased substantially over the last decades.  The development of retinoblastoma can be explained by the two-hit model. According to the two-hit model, both alleles need to be affected, so two events are necessary for the retinal cell or cells to develop into tumors. The first mutational event can be inherited (germline or constitutional), which will then be present in all cells in the body. The second “hit” results in the loss of the remaining normal allele (gene) and occurs within a particular retinal cell. In the sporadic, nonheritable form of retinoblastoma, both mutational events occur within a single retinal cell after fertilization (somatic events); sporadic retinoblastoma tends to be unilateral.  Several methods have been developed to detect the "RB1" gene mutations. Attempts to correlate gene mutations to the stage at presentation have not shown convincing evidence of a correlation.

MYCN.

Somatic amplification of the "MYCN" oncogene is responsible for some cases of nonhereditary, early-onset, aggressive, unilateral retinoblastoma. Although "MYCN" amplification accounted for only 1.4% of retinoblastoma cases, researchers identified it in 18% of infants diagnosed at less than 6 months of age. Median age at diagnosis for "MYCN" retinoblastoma was 4.5 months, compared with 24 months for those who had nonfamilial unilateral disease with two "RB1 "gene mutations.

Diagnosis.

Screening for retinoblastoma should be part of a "well baby" screening for newborns during the first 3 months of life, to include:

Classification.

The two forms of the disease are a heritable form and nonheritable form (all cancers are considered genetic in that mutations of the genome are required for their development, but this does not imply that they are heritable, or transmitted to offspring). Around 55% of children with retinoblastoma have the nonheritable form. If no history of the disease exists within the family, the disease is labeled "sporadic", but this does not necessarily indicate that it is the nonheritable form. Bilateral retinoblastomas are commonly heritable, while unilateral retinoblastomas are commonly nonheritable.  In about two-thirds of cases, only one eye is affected (unilateral retinoblastoma); in the other third, tumors develop in both eyes (bilateral retinoblastoma). The number and size of tumors on each eye may vary. In certain cases, the pineal gland or the suprasellar or parasellar region (or in very rare cases other midline intracranial locations) is also affected (trilateral retinoblastoma). The position, size, and quantity of tumors are considered when choosing the type of treatment for the disease.

Differential diagnosis.

If the eye examination is abnormal, further testing may include imaging studies, such as computerized tomography (CT), magnetic resonance imaging (MRI), and ultrasound. CT and MRI can help define the structure abnormalities and reveal any calcium depositions. Ultrasound can help define the height and thickness of the tumor. Bone marrow examination or lumbar puncture may also be done to determine any metastases to bones or the brain.

Morphology.

Gross and microscopic appearances of retinoblastoma are identical in both hereditary and sporadic types. Macroscopically, viable tumor cells are found near blood vessels, while zones of necrosis are found in relatively avascular areas. Microscopically, both undifferentiated and differentiated elements may be present. Undifferentiated elements appear as collections of small, round cells with hyperchromatic nuclei; differentiated elements include Flexner-Wintersteiner rosettes, Homer Wright rosettes, and fleurettes from photoreceptor differentiation.

Genetic testing.

Identifying the "RB1" gene mutation that led to a child's retinoblastoma can be important in the clinical care of the affected individual and in the care of (future) siblings and offspring. It may run in the family.

Treatment.

The priority of retinoblastoma treatment is to preserve the life of the child, then to preserve vision, and then to minimize complications or side effects of treatment. The exact course of treatment depends on the individual case and is decided by the ophthalmologist in discussion with the paediatric oncologist. Children with involvement of both eyes at diagnosis usually require multimodality therapy (chemotherapy, local therapies).  The various treatment modalities for retinoblastoma includes:

Prognosis.

In the developed world, retinoblastoma has one of the best cure rates of all childhood cancers (95-98%), with more than 90% of sufferers surviving into adulthood. In the UK, around 40 to 50 new cases are diagnosed each year.  Good prognosis depends upon early presentation of the child in health facility. Late presentation is associated with a poor prognosis.  Survivors of hereditary retinoblastoma have a higher risk of developing other cancers later in life.

Epidemiology.

Retinoblastoma presents with cumulative lifetime incidence rate of one case of retinoblastoma per 18000 to 30000 live births worldwide. A higher incidence is noted in developing countries, which has been attributed to lower socioeconomic status and the presence of human papilloma virus sequences in the retinoblastoma tissue.  Almost 80% of children with retinoblastoma are diagnosed before 3 years of age and diagnosis in children above 6 years of age is extremely rare. In the UK, bilateral cases usually present within 14 to 16 months, while diagnosis of unilateral cases peaks between 24 and 30 months.

Retinoblastoma (Rb) is a rare form of cancer that rapidly develops from the immature cells of a retina, the light-detecting tissue of the eye. It is the most common primary malignant intraocular cancer in children, and it is almost exclusively found in young children.


Description, ecology and uses.

Sainfoins are mostly subtropical plants, but their range extends throughout Europe as far north as southern Sweden. These plants grow on grassland, agricultural land and wasteland. The leaves are pinnate, alternate, with 6 to 14 pairs of oblong to linear leaflets. Sainfoins have pale pink flowers, typically blooming between June and September and pollinated by honey bees and solitary bees. The rounded single-seeded pods bear prominent spikes or similar protrusions in many species, enabling them to cling to the fur of large mammals and be thus distributed.  These highly nutritious plants were an important forage for heavy working horses in agriculture, and are still an excellent source of nectar for honey production as well as pollen for bee food. Because sainfoins are rich in tannins which protect proteins from hydrolysis in the rumen, the proteins are instead absorbed in the abomasum. "Onobrychis" typically have a deep taproot and so are very drought resistant, but do not recover well from overgrazing. Adapted to slow but steady growth in the arid steppe belt of Eurasia, sainfoins are difficult to establish as pasture, are not persistent in grassland, and only yield one crop of hay or seeds per year. Thus they are seldom grown in any significant extent, though "O. viciifolia" is met with somewhat more regularly.  "Onobrychis" species are used as food plants by the caterpillars of some Lepidoptera species, such as the case-bearer moth "Coleophora colutella" (recorded on "O. saxatilis") and the Damon Blue ("Polyommatus damon") butterfly.

Nutritional benefits and the latest research.

Sainfoin provides a superb forage for grazing animals and voluntary intake of sainfoin by cattle and sheep is 20% higher than for grass. Unlike many other legumes, it is non-bloating and is known to have anthelmintic properties, so reducing the problems associated with livestock worms. Sainfoin contains condensed tannins, and it is these that protect animals against bloat. Sainfoin has also been shown to increase protein absorption. This, combined with its other health benefits, mean that animals grazing sainfoin have very rapid liveweight gains, so young stock can be finished sooner and with very good carcass grades. Sainfoin is therefore extremely useful to low input and organic farmers. Yields can be very high at around 16t DM per hectare.  Methods and research techniques have been studied and developed to look specifically at Sainfoin polyphenols which include tannins and flavonoids. There are significant differences between Sainfoin types and this will lead to further development of Sainfoin plant breeding.  One method for improving nitrogen utilisation by ruminants and reduce greenhouse gases (CH4, N2O), without altering their nitrogen and energy value, is to use forages that contain condensed tannins, such as sainfoin. The nutritive value of sainfoin, despite its lower nitrogen content than lucerne, is high. Future research, on the nutritional impact of condensed tannins is likely not only be based on condensed tannin content, but also include structure-activity considerations. The results obtained, with sheep at maintenance fed a diet containing only sainfoin will be tested with producing animals, for example growing sheep and cattle, lactating ewes, goats or cows. In producing animals the diet will comprise different forage sources and supplement feeds. Sainfoin is seldom used as a pure crop and is generally introduced in pasture in a grass-legume mix with cocksfoot ("Dactylis"), ryegrass ("Lolium") or with other legumes such as red clover, white clover or lucerne. Results have shown the choice of the variety is important. A variety like Esparcette, characterised by the highest condensed tannin content, may provide beneficial effects with a lower proportion in a mixture with other legumes. Preserving legumes, as silage, is a good way to provide an on-farm source of home-grown energy and protein, offers advantages over traditional haymaking, being less weather-dependent, and allows a high quality of forage during the harvesting period. In particular, wrapped silage bales of sainfoin have great potential in animal nutrition and can be used by farmers, as found that condensed tannin effects were not reduced by this mode of preservation.

Etymology.

"Onobrychis" means "devoured by donkeys", from Ancient Greek "ónos" (ὄνος, "donkey") and "brýkein" (βρύκειν, "to eat greedily"). This refers to sainfoin's good properties as a forage plant for large mammalian herbivores.  "Sainfoin" is derived from Old French "sain foin" ("healthy hay"). In the words of the 16th-century soil scientist Olivier de Serres: "The herb is called "sain-foin" in France, in Italy "herba medica", in Provence and the Languedoc "luzerne". From the inordinate praise the plant has been given, for its medical virtues and for fattening the livestock that graze on it, comes the term "sain"."  In northern European languages that have been less influenced by French, the plants' name usually derives from "esparceto", the Provençal term for the similar-looking and closely related sweetvetches ("Hedysarum"). Examples are Danish "esparsette", Dutch "esparcette", German "Esparsette", Lithuanian "esparceta", Polish "sparceta", Russian "espartset" (Эспарцет) and Swedish "esparsett". Meanwhile, the Occitan name of sainfoin, "luzerne", has in many languages come to mean species of the related genus "Medicago", in particular Alfalfa ("M. sativa").  The native name of the Cock's Head ("O. caput-galli") is one of the few words of the extinct Dacian language that have been recorded. The Dacians called this plant "aniarsexe" or "aniassexie".  In George Orwell's "Coming Up for Air", travelling salesman George Bowling regularly reminisces about the smell of sainfoin in his father's seed shop in Lower Binfield.

List of species.

The following species are considered at least provisionally valid by the International Legume Database & Information Service; some notable subspecies are also listed:

Onobrychis, the sainfoins, are Eurasian perennial herbs of the legume family (Fabaceae). Including doubtfully distinct species and provisionally accepted taxa, about 150 species are presently known. The Flora Europaea lists 23 species of "Onobrychis"; the main centre of diversity extends from Central Asia to Iran, with 56 species – 27 of which are endemic – in the latter country alone. "O. viciifolia" is naturalized throughout many countries in Europe and North America grasslands on calcareous soils.


History of binary codes.

The modern binary number system, the basis for binary code, was invented by Gottfried Leibniz in 1689 and appears in his article "Explication de l'Arithmétique Binaire". The full title is translated into English as the "Explanation of the binary arithmetic", which uses only the characters 1 and 0, with some remarks on its usefulness, and on the light it throws on the ancient Chinese figures of Fu Xi." (1703). Leibniz's system uses 0 and 1, like the modern binary numeral system. Leibniz encountered the "I Ching" through French Jesuit Joachim Bouvet and noted with fascination how its hexagrams correspond to the binary numbers from 0 to 111111, and concluded that this mapping was evidence of major Chinese accomplishments in the sort of philosophical visual binary mathematics he admired. Leibniz saw the hexagrams as an affirmation of the universality of his own religious belief.  Binary numerals were central to Leibniz's theology. He believed that binary numbers were symbolic of the Christian idea of "creatio ex nihilo" or creation out of nothing. Leibniz was trying to find a system that converts logic’s verbal statements into a pure mathematical one. After his ideas were ignored, he came across a classic Chinese text called "I Ching" or ‘Book of Changes’, which used 64 hexagrams of six-bit visual binary code. The book had confirmed his theory that life could be simplified or reduced down to a series of straightforward propositions. He created a system consisting of rows of zeros and ones. During this time period, Leibniz had not yet found a use for this system.  Binary systems predating Leibniz also existed in the ancient world. The aforementioned "I Ching" that Leibniz encountered dates from the 9th century BC in China. The binary system of the "I Ching", a text for divination, is based on the duality of yin and yang. Slit drums with binary tones are used to encode messages across Africa and Asia. The Indian scholar Pingala (around 5th–2nd centuries BC) developed a binary system for describing prosody in his Chandashutram. The residents of the island of Mangareva in French Polynesia were using a hybrid binary-decimal system before 1450. In the 11th century, scholar and philosopher Shao Yong developed a method for arranging the hexagrams which corresponds, albeit unintentionally, to the sequence 0 to 63, as represented in binary, with yin as 0, yang as 1 and the least significant bit on top. The ordering is also the lexicographical order on sextuples of elements chosen from a two-element set.  In 1605 Francis Bacon discussed a system whereby letters of the alphabet could be reduced to sequences of binary digits, which could then be encoded as scarcely visible variations in the font in any random text. Importantly for the general theory of binary encoding, he added that this method could be used with any objects at all: "provided those objects be capable of a twofold difference only; as by Bells, by Trumpets, by Lights and Torches, by the report of Muskets, and any instruments of like nature".  George Boole published a paper in 1847 called 'The Mathematical Analysis of Logic' that describes an algebraic system of logic, now known as Boolean algebra. Boole's system was based on binary, a yes-no, on-off approach that consisted of the three most basic operations: AND, OR, and NOT. This system was not put into use until a graduate student from Massachusetts Institute of Technology, Claude Shannon, noticed that the Boolean algebra he learned was similar to an electric circuit. Shannon wrote his thesis in 1937, which implemented his findings. Shannon's thesis became a starting point for the use of the binary code in practical applications such as computers, electric circuits, and more.

Other forms of binary code.

The bit string is not the only type of binary code: in fact, a binary system in general, is any system that allows only two choices such as a switch in an electronic system or a simple true or false test.

Braille.

Braille is a type of binary code that is widely used by the blind to read and write by touch, named for its creator, Louis Braille. This system consists of grids of six dots each, three per column, in which each dot has two states: raised or not raised. The different combinations of raised and flattened dots are capable of representing all letters, numbers, and punctuation signs.

Bagua.

The "bagua" are diagrams used in "feng shui," Taoist cosmology and "I Ching" studies. The "ba gua" consists of 8 trigrams; "bā" meaning 8 and "guà" meaning divination figure. The same word is used for the 64 guà (hexagrams). Each figure combines three lines ("yáo") that are either broken ("yin") or unbroken ("yang"). The relationships between the trigrams are represented in two arrangements, the primordial, "Earlier Heaven" or "Fuxi" "bagua", and the manifested, "Later Heaven,"or "King Wen" "bagua." (See also, the King Wen sequence of the 64 hexagrams).

Coding systems.

ASCII code.

The American Standard Code for Information Interchange (ASCII), uses a 7-bit binary code to represent text and other characters within computers, communications equipment, and other devices. Each letter or symbol is assigned a number from 0 to 127. For example, lowercase "a" is represented by codice_2 as a bit string (which is "97" in decimal).

Binary-coded decimal.

Binary-coded decimal (BCD) is a binary encoded representation of integer values that uses a 4-bit nibble to encode decimal digits. Four binary bits can encode up to 16 distinct values; but, in BCD-encoded numbers, only the first ten values in each nibble are legal, and encode the decimal digits zero, through nine. The remaining six values are illegal and may cause either a machine exception or unspecified behavior, depending on the computer implementation of BCD arithmetic.  BCD arithmetic is sometimes preferred to floating-point numeric formats in commercial and financial applications where the complex rounding behaviors of floating-point numbers is inappropriate.

Current uses of binary.

Most modern computers use binary encoding for instructions and data. CDs, DVDs, and Blu-ray Discs represent sound and video digitally in binary form. Telephone calls are carried digitally on long-distance and mobile phone networks using pulse-code modulation, and on voice over IP networks.

Weight of binary codes.

The weight of a binary code, as defined in the table of constant-weight codes, is the Hamming weight of the binary words coding for the represented words or sequences.

A binary code represents text, computer processor instructions, or any other data using a two-symbol system. The two-symbol system used is often "0" and "1" from the binary number system. The binary code assigns a pattern of binary digits, also known as bits, to each character, instruction, etc. For example, a binary string of eight bits can represent any of 256 possible values and can, therefore, represent a wide variety of different items.


Shipwreck.

The "White Ship" was a newly refitted vessel captained by Thomas FitzStephen ("Thomas filz Estienne"), whose father Stephen FitzAirard ("Estienne filz Airard") had been captain of the ship "Mora" for William the Conqueror when he invaded England in 1066. Thomas offered his ship to Henry I of England to return to England from Barfleur in Normandy. Henry had already made other arrangements, but allowed many in his retinue to take the "White Ship," including his heir, William Adelin; his illegitimate son Richard of Lincoln; his illegitimate daughter Matilda FitzRoy, Countess of Perche; and many other nobles. According to chronicler Orderic Vitalis, the crew asked William Adelin for wine and he supplied it to them in great abundance. By the time the ship was ready to leave there were about 300 people on board, although some, including the future king Stephen of Blois, had disembarked due to the excessive binge drinking before the ship sailed.  The ship's captain, Thomas FitzStephen, was ordered by the revellers to overtake the king's ship, which had already sailed. The "White Ship" was fast, of the best construction and had recently been fitted with new materials, which made the captain and crew confident they could reach England first. But when it set off in the dark, its port side struck a submerged rock called "Quillebœuf", and the ship quickly capsized. William Adelin got into a small boat and could have escaped but turned back to try to rescue his half-sister, Matilda, when he heard her cries for help. His boat was swamped by others trying to save themselves, and William drowned along with them. According to Orderic Vitalis, Berold (Beroldus or Berout), a butcher from Rouen, was the sole survivor of the shipwreck by clinging to the rock. The chronicler further wrote that when Thomas FitzStephen came to the surface after the sinking and learned that William Adelin had not survived, he let himself drown rather than face the King.  One legend holds that the ship was doomed because priests were not allowed to board it and bless it with holy water in the customary manner. For a complete list of those who did or did not travel on the "White Ship", see Victims of the "White Ship" disaster.

Repercussions.

A direct result of William Adelin's death was the period known as the Anarchy. The "White Ship" disaster had left Henry I with only one legitimate child, a second daughter named Matilda. Although Henry I had forced his barons to swear an oath to support Matilda as his heir on several occasions, a woman had never ruled in England in her own right. Matilda was also unpopular because she was married to Geoffrey V, Count of Anjou, a traditional enemy of England's Norman nobles. Upon Henry's death in 1135, the English barons were reluctant to accept Matilda as queen regnant.  One of Henry I's male relatives, Stephen of Blois, the king's nephew by his sister Adela, usurped Matilda as well as his older brothers William and Theobald to become king. Stephen had allegedly planned to travel on the "White Ship" but had disembarked just before it sailed; Orderic Vitalis attributes this to a sudden bout of diarrhoea.  After Henry I's death, Matilda and her husband Geoffrey of Anjou, the founder of the Plantagenet dynasty, launched a long and devastating war against Stephen and his allies for control of the English throne. The Anarchy dragged from 1135 to 1153 with devastating effect, especially in southern England.  Contemporary historian William of Malmesbury wrote:

The White Ship (; Medieval Latin: "Candida navis") was a vessel that sank in the English Channel near the Normandy coast off Barfleur, on 25 November 1120. Only one of the around 300 people aboard survived. Those who drowned included William Adelin, the only legitimate son and heir of King Henry I of England, his half-sister Matilda, his half-brother Richard, Richard d'Avranches, 2nd Earl of Chester, and Geoffrey Ridel (royal justice). William Adelin's death led to a succession crisis and a period of civil war in England known as the Anarchy.


Etymology.

The name Cerdic is thought by most scholars to be Brittonic – a form of the name Ceretic – rather than Germanic in origin. According to the Brittonic origin hypothesis, Cerdic is derived from the British name "*Caratīcos" or "*Corotīcos". This may indicate that Cerdic was a native Briton, and that his dynasty became Anglicised over time. This view is supported by the potentially non-Germanic names of some of his descendants including Ceawlin, Cedda and Caedwalla.

Background.

The "Anglo-Saxon Chronicle" provides a pedigree tracing Cerdic's ancestry back to Wōden and the antediluvian patriarchs. Kenneth Sisam has shown that this pedigree resulted from a process of elaboration upon a root pedigree borrowed from the kings of Bernicia, and hence prior to Cerdic himself it has no historical basis.  J.N.L. Myres noted that when Cerdic and Cynric first appear in the "Anglo-Saxon Chronicle" in s.a. 495 they are described as "ealdormen", which at that point in time was a fairly junior rank. Myres remarks that,  It is thus odd to find it used here to describe the leaders of what purports to be an independent band of invaders, whose origins and authority are not otherwise specified. It looks very much as if a hint is being conveyed that Cerdic and his people owed their standing to having been already concerned with administrative affairs under Roman authority on this part of the Saxon Shore. Furthermore, it is not until s.a. 519 that Cerdic and Cynric are recorded as "beginning to reign", suggesting that they ceased being dependent vassals or ealdormen and became independent kings in their own right.  Summing up, Myres believed that,  It is thus possible... to think of Cerdic as the head of a partly British noble family with extensive territorial interests at the western end of the Litus Saxonicum. As such he may well have been entrusted in the last days of Roman, or sub-Roman authority with its defence. He would then be what in later Anglo-Saxon terminology could be described as an ealdorman.... If such a dominant native family as that of Cerdic had already developed blood-relationships with existing Saxon and Jutish settlers at this end of the Saxon Shore, it could very well be tempted, once effective Roman authority had faded, to go further. It might have taken matters into its own hands and after eliminating any surviving pockets of resistance by competing British chieftains, such as the mysterious Natanleod of annal 508, it could 'begin to reign' without recognizing in future any superior authority.  Cerdic's father, "Elesa", has been identified by some scholars with the Romano-British Elasius, the "chief of the region", met by Germanus of Auxerre.

King of Wessex.

According to the "Anglo-Saxon Chronicle", Cerdic landed in what is today Hampshire in 495 with his son Cynric in five ships. He is said to have fought a Brittonic king named Natanleod at "Natanleaga" and killed him thirteen years later (in 508) and to have fought at "Cerdicesleag" in 519. "Natanleaga" is commonly identified as Netley Marsh in Hampshire and "Cerdicesleag" as Charford (Cerdic's Ford). The conquest of the Isle of Wight is also mentioned among his campaigns, and it was later given to his kinsmen, Stuf and Wihtgar (who had supposedly arrived with the West Saxons in 514). Cerdic is said to have died in 534 and was succeeded by his son Cynric or possibly Creoda of Wessex.  The early history of Wessex in the "Chronicle" has been considered unreliable, with duplicate reports of events and seemingly contradictory information. David Dumville has suggested that Cerdic's true regnal dates are 538–554. Some scholars suggest that Cerdic was the Saxon leader defeated by the Britons at the Battle of Mount Badon, which was probably fought in 490 (and possibly later, but not later than 518). This cannot be the case if Dumville is correct, and others assign this battle to Ælle or another Saxon leader, so it appears likely that the origins of the kingdom of Wessex are more complex than the version provided by the surviving traditions.  Some scholars have gone so far as to suggest that Cerdic is purely a legendary figure, but this is a minority view. The earliest source for Cerdic, the "Anglo-Saxon Chronicle", was put together in the late ninth century; though it probably does record the extant tradition of the founding of Wessex, the intervening four hundred years mean that the account cannot be assumed to be accurate. The annals of the Anglo-Saxon Chronicle, along with the genealogical descents embedded in that source's accounts of later kings, describe Cerdic's succession by his son Cynric. However, the Genealogical Regnal List that served as preface to the Chronicle manuscripts instead interposes a generation between them, indicating that Cerdic was father of Creoda and grandfather of Cynric.  Descent from Cerdic became a necessary criterion for later kings of Wessex, and he was claimed ancestor of Ecgberht, King of Wessex, progenitor of the English royal house and subsequent rulers of England and Britain.

See also.

House of Wessex family tree

Cerdic (; ) is cited in the "Anglo-Saxon Chronicle" as a leader of the Anglo-Saxon settlement of Britain, being the founder and first king of Saxon Wessex, reigning from 519 to 534 AD. Subsequent kings of Wessex were each claimed by the "Chronicle" to descend in some manner from Cerdic. His origin, ethnicity, and even his very existence have been extensively disputed.


Early life.

Negroponte was born to Dimitrios Negrepontis (), a Greek shipping magnate and alpine skier, and grew up in New York City's Upper East Side. He has three brothers. His elder one, John Negroponte, is the former United States Deputy Secretary of State. Michael Negroponte is an Emmy Award-winning filmmaker. George Negroponte is an artist and was President of the Drawing Center from 2002 to 2007.  He attended Buckley School in New York, Fay School in Massachusetts, Le Rosey in Switzerland, and The Choate School (now Choate Rosemary Hall) in Wallingford, Connecticut, from which he graduated in 1961. Subsequently, he studied at MIT as both an undergraduate and graduate student in Architecture where his research focused on issues of computer-aided design. He earned a master's degree in architecture from MIT in 1966. Despite his accomplished academic career, Negroponte has spoken publicly about his dyslexia and his difficulty in reading.

Career.

MIT.

Negroponte joined the faculty of MIT in 1966. For several years thereafter he divided his teaching time between MIT and several visiting professorships at Yale, Michigan and the University of California, Berkeley.  In 1967, Negroponte founded MIT's Architecture Machine Group, a combination lab and think tank which studied new approaches to human-computer interaction. In 1985, Negroponte created the MIT Media Lab with Jerome B. Wiesner. As director, he developed the lab into a pre-eminent laboratory for new media and a high-tech playground for investigating the human-computer interface. Negroponte also became a proponent of intelligent agents and personalized electronic newspapers, for which he popularized the term the Daily Me.

"Wired".

In 1992, Negroponte became involved in the creation of "Wired Magazine" as the first investor. From 1993 to 1998, he contributed a monthly column to the magazine in which he reiterated a basic theme: "Move bits, not atoms."  Negroponte expanded many of the ideas from his "Wired" columns into a bestselling book "Being Digital" (1995), which made famous his forecasts on how the interactive world, the entertainment world and the information world would eventually merge. "Being Digital" was a bestseller and was translated into some forty languages. Negroponte is a digital optimist who believed that computers would make life better for everyone. However, critics such as Cass Sunstein have criticised his techno-utopian ideas for failing to consider the historical, political and cultural realities with which new technologies should be viewed.  In the 1980s Negroponte predicted that wired technologies such as telephones would become unwired by using airwaves instead of wires or fiber optics, and that unwired technologies such as televisions would become wired—a prediction commonly referred to as the Negroponte switch.

Later career.

In 2000, Negroponte stepped down as director of the Media Lab as Walter Bender took over as Executive Director. However, Negroponte retained the role of laboratory chairman. When Frank Moss was appointed director of the lab in 2006, Negroponte stepped down as lab chairman to focus more fully on his work with One Laptop Per Child (OLPC) although he retains his appointment as professor at MIT (Professor Post-Tenure of Media Arts and Sciences). In November 2005, at the World Summit on the Information Society held in Tunis, Negroponte unveiled the concept of a $100 laptop computer, The Children's Machine, designed for students in the developing world. The price has increased to US$180, however. The project is part of a broader program by One Laptop Per Child, a nonprofit organization started by Negroponte and other Media Lab faculty to extend Internet access in developing countries.  Negroponte is an active angel investor and has invested in over 30 startup companies over the last 30 years, including Zagats, Wired, Ambient Devices, Skype and Velti. He has sat on several boards, including Motorola (listed on the New York Stock Exchange) and Velti (listed on the NASDAQ and formerly on the London Stock Exchange ). He is also on the advisory board of TTI/Vanguard. In August 2007, he was appointed to a five-member special committee with the objective of assuring the continued journalistic and editorial integrity and independence of the Wall Street Journal and other Dow Jones & Company publications and services. The committee was formed as part of the merger of Dow Jones with News Corporation. Negroponte's fellow founding committee members are Louis Boccardi, Thomas Bray, Jack Fuller, and the late former Congresswoman Jennifer Dunn.  Negroponte has influenced modern day futurists such as David Houle.

Epstein controversy.

According to reporting from the MIT Technology Review, in response to the controversy of the MIT Media Lab accepting funding from Jeffrey Epstein five years after Epstein's conviction for sex trafficking minors, Negroponte told MIT staff, "If you wind back the clock, I would still say, 'Take it.'"  Negroponte was reported to have said that in the fund-raising world these types of occurrences were not out of the ordinary, and they shouldn’t be reason enough to cut off business relationships. His comments supporting the donation from a convicted child sex offender reportedly left some of his listeners "stunned" and reduced one woman present to tears.

Nicholas Negroponte (born December 1, 1943) is a Greek American architect. He is the founder and chairman Emeritus of Massachusetts Institute of Technology's Media Lab, and also founded the One Laptop per Child Association (OLPC). Negroponte is the author of the 1995 bestseller ‘Being Digital’ translated into more than forty languages.


Life.

Ferdinand Schwarzmann von Hebra graduated in medicine in 1841 at the University of Vienna. He was influenced by Carl Freiherr von Rokitansky, one of the founders of modern pathological anatomy.  While still a young man, Hebra wrote one of the most influential books on dermatology of all times, the "Atlas der Hautkrankeiten" ("Atlas of skin diseases"), with phenomenal illustrations by two of the leading medical illustrators of Austria, Anton Elfinger (1821–1864) and Carl Heitzmann (1836–1896).  In 1844 Ferdinand von Hebra discovered the cause of scabies.  In the second half of the 19th century, Hebra introduced resurfacing and restoring skin with chemical peel. He used exfoliative agents, like phenol, croton oil, nitric acid in various cautious combination for treating freckles and skin irregularities.

Semmelweis and Hebra.

An early supporter of Ignaz Semmelweis and the editor of a leading Austrian medical journal, Hebra announced Semmelweis's discovery that handwashing with chloride of lime reduces the incidence of puerperal fever in the December 1847 and April 1848 issues of the Viennese medical journal. Hebra claimed that Semmelweis's work had a practical significance comparable to that of Edward Jenner's introduction of cowpox inoculations to prevent smallpox.  Due to Semmelweis's suffering from severe depression and other mental problems, János Balassa signed a document which committed him to a mental institution, and on 30 July 1865 Hebra, under the pretense of taking him to visit one of Hebra's "new Institutes", lured Semmelweis into a Viennese asylum for the insane located in the Lazarettgasse ("Landes-Irren-Anstalt in der Lazarettgasse"). On arrival there, Semmelweis guessed what was happening and tried to leave, but he was forcibly subdued by the asylum's guards and died two weeks later from a gangrenous wound which may have been caused by the struggle.

Ferdinand Karl Franz Schwarzmann, Ritter von Hebra (7 September 1816, in Brno, Moravia – 5 August 1880 in Vienna, Austria-Hungary) was an Austrian physician and dermatologist known as the founder of the New Vienna School of Dermatology, an important group of physicians who established the foundations of modern dermatology.


Genetics.

Factor VIII was first characterized in 1984 by scientists at Genentech. The gene for factor VIII is located on the X chromosome (Xq28). The gene for factor VIII presents an interesting primary structure, as another gene is embedded in one of its introns.

Structure.

Factor VIII protein consists of six domains: A1-A2-B-A3-C1-C2, and is homologous to factor V.  The A domains are homologous to the A domains of the copper-binding protein ceruloplasmin. The C domains belong to the phospholipid-binding discoidin domain family, and the C2 domain mediate membrane binding.  Activation of factor VIII to factor VIIIa is done by cleavage and release of the B domain. The protein is now divided to a heavy chain, consisting of the A1-A2 domains, and a light chain, consisting of the A3-C1-C2 domains. Both form non-covalently a complex in a calcium-dependent manner. This complex is the pro-coagulant factor VIIIa.

Physiology.

FVIII is a glycoprotein procofactor. Although the primary site of release in humans is ambiguous, it is synthesized and released into the bloodstream by the vascular, glomerular, and tubular endothelium, and the sinusoidal cells of the liver. Hemophilia A has been corrected by liver transplantation. Transplanting hepatocytes was ineffective, but liver endothelial cells were effective.  In the blood, it mainly circulates in a stable noncovalent complex with von Willebrand factor. Upon activation by thrombin (factor IIa), it dissociates from the complex to interact with factor IXa in the coagulation cascade. It is a cofactor to factor IXa in the activation of factor X, which, in turn, with its cofactor factor Va, activates more thrombin. Thrombin cleaves fibrinogen into fibrin which polymerizes and crosslinks (using factor XIII) into a blood clot.  No longer protected by vWF, activated FVIII is proteolytically inactivated in the process (most prominently by activated protein C and factor IXa) and quickly cleared from the blood stream.  Factor VIII is not affected by liver disease. In fact, levels usually are elevated in such instances.

Medical use.

FVIII concentrated from donated blood plasma, or alternatively recombinant FVIIa can be given to hemophiliacs to restore hemostasis.  Antibody formation to factor VIII can also be a major concern for patients receiving therapy against bleeding; the incidence of these inhibitors is dependent of various factors, including the factor VIII product itself.

Contamination scandal.

In the 1980s, some pharmaceutical companies such as Baxter International and Bayer sparked controversy by continuing to sell contaminated factor VIII after new heat-treated versions were available. Under FDA pressure, unheated product was pulled from US markets, but was sold to Asian, Latin American, and some European countries. The product was tainted with HIV, a concern that had been discussed by Bayer and the U.S. Food and Drug Administration (FDA).  In the early 1990s, pharmaceutical companies began to produce recombinant synthesized factor products, which now prevent nearly all forms of disease transmission during replacement therapy.

History.

Factor VIII was first discovered in 1937, but it was not until 1979 that its purification by Edward Tuddenham and coworkers led to the molecular identification of the protein.

Factor VIII (FVIII) is an essential blood-clotting protein, also known as anti-hemophilic factor (AHF). In humans, factor VIII is encoded by the "F8" gene. Defects in this gene result in hemophilia A, a recessive X-linked coagulation disorder. Factor VIII is produced in liver sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot.