Thomas Jefferson

Thomas Jefferson was an American statesman, lawyer, architect and Founding Father who served as the third president of the United States from 1801 to 1809. He served as the second vice president of the United States from 1797 to 1801; the principal author of the Declaration of Independence, Jefferson was a proponent of democracy and individual rights, motivating American colonists to break from the Kingdom of Great Britain and form a new nation. During the American Revolution, he represented Virginia in the Continental Congress that adopted the Declaration, drafted the law for religious freedom as a Virginia legislator, served as the second Governor of Virginia from 1779 to 1781, during the American Revolutionary War, he became the United States Minister to France in May 1785, subsequently, the nation's first secretary of state under President George Washington from 1790 to 1793. Jefferson and James Madison organized the Democratic-Republican Party to oppose the Federalist Party during the formation of the First Party System.

With Madison, he anonymously wrote the provocative Kentucky and Virginia Resolutions in 1798 and 1799, which sought to strengthen states' rights by nullifying the federal Alien and Sedition Acts. As president, Jefferson pursued the nation's shipping and trade interests against Barbary pirates and aggressive British trade policies, he organized the Louisiana Purchase doubling the country's territory. As a result of peace negotiations with France, his administration reduced military forces, he was reelected in 1804. Jefferson's second term was beset with difficulties at home, including the trial of former vice president Aaron Burr. American foreign trade was diminished when Jefferson implemented the Embargo Act of 1807, in response to British threats to U. S. shipping. In 1803, Jefferson began a controversial process of Indian tribe removal to the newly organized Louisiana Territory, he signed the Act Prohibiting Importation of Slaves in 1807. After retiring from public office, Jefferson founded the University of Virginia.

Jefferson, while a planter and politician, mastered many disciplines, which ranged from surveying and mathematics to horticulture and mechanics. He was an architect in the classical tradition. Jefferson's keen interest in religion and philosophy led to his presidency of the American Philosophical Society. A philologist, Jefferson knew several languages, he corresponded with many prominent people. His only full-length book is Notes on the State of Virginia, considered the most important American book published before 1800. Although Jefferson is regarded as a leading spokesman for democracy and republicanism in the era of the Enlightenment, some modern scholarship has been critical of Jefferson, finding a contradiction between his ownership and trading of many slaves that worked his plantations, his famous declaration that "all men are created equal". Although the matter remains a subject of debate, most historians believe that Jefferson had a sexual relationship with his slave Sally Hemings, a mixed-race woman, a half-sister to his late wife and that he fathered at least one of her children.

Presidential scholars and historians praise Jefferson's public achievements, including his advocacy of religious freedom and tolerance in Virginia. Jefferson continues to rank among U. S. presidents. Thomas Jefferson was born on April 13, 1743, at the family home in Shadwell in the Colony of Virginia, the third of ten children, he was of English, Welsh and was born a British subject. His father Peter Jefferson was a surveyor who died when Jefferson was fourteen. Peter Jefferson moved his family to Tuckahoe Plantation in 1745 upon the death of William Randolph, the plantation's owner and Jefferson's friend, who in his will had named him guardian of his children; the Jeffersons returned to Shadwell in 1752, where Peter died in 1757. Thomas inherited 5,000 acres of land, including Monticello, he assumed full authority over his property at age 21. Jefferson began his education beside the Randolph children with tutors at Tuckahoe. Thomas' father, was self-taught, regretting not having a formal education, he entered Thomas into an English school early, at age five.

In 1752, at age nine, he began attending a local school run by a Scottish Presbyterian minister and began studying the natural world, for which he grew to love. At this time he began studying Latin and French, while learning to ride horses. Thomas read books from his father's modest library, he was taught from 1758 to 1760 by Reverend James Maury near Gordonsville, where he studied history and the classics while boarding with Maury's family. During this period Jefferson came to know and befriended various American Indians, including the famous Cherokee chief Ontasseté who stopped at Shadwell to visit, on their way to Williamsburg to trade. During the two years Jefferson was with the Maury family, he traveled to Williamsburg and was a guest of Colonel Dandridge, father of Martha Washington. In Williamsburg the young Jefferson met and came to admire Patrick Henry, eight years his senior, sharing a common interest of violin playing. Jefferson entered the College of William & Mary in Williamsburg, Virginia, at age 16 and studied mathematics and philosophy under Professor Wi


The rifamycins are a group of antibiotics that are synthesized either by the bacterium Amycolatopsis rifamycinica or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are effective against mycobacteria, are therefore used to treat tuberculosis and mycobacterium avium complex infections; the rifamycin group includes the "classic" rifamycin drugs as well as the rifamycin derivatives rifampicin, rifapentine and rifaximin. Rifamycin, sold under the trade name Aemcolo, is approved in the United States for treatment of travelers' diarrhea in some circumstances. Streptomyces mediterranei was first isolated in 1957 from a soil sample collected near the beach-side town of St Raphael in southern France; the name was given by two microbiologists working with the Italian drug company Group Lepetit SpA in Milan, the Italian Grazia Beretta, Pinhas Margalith of Israel. In 1969, the bacterium was renamed Nocardia mediterranei when another scientist named Thiemann found that it has a cell wall typical of the Nocardia species.

In 1986, the bacterium was renamed again Amycolatopsis mediterranei, as the first species of a new genus, because a scientist named Lechevalier discovered that the cell wall lacks mycolic acid and is not able to be infected by the Nocardia and Rhodococcus phages. Based on 16S ribosomal RNA sequences, Bala et al. renamed the species in 2004 Amycolatopsis rifamycinica. Rifamycins were first isolated in 1957 from a fermentation culture of Streptomyces mediterranei at the laboratory of Gruppo Lepetit SpA in Milan by two scientist named Piero Sensi and Maria Teresa Timbal, working with the Israeli scientist Pinhas Margalith. A family of related antibiotics was discovered referred to as Rifamycin A, B, C, D, E; the only component of this mixture sufficiently stable to isolate in a pure form was Rifamycin B, poorly active. However, further studies showed that while Rifamycin B was inactive, it was spontaneously oxidized and hydrolyzed in aqueous solutions to yield the active Rifamycin S. Simple reduction of Rifamycin S yielded the hydroquinone form called Rifamycin SV, which became the first member of this class to enter clinical use as an intravenous antibiotic.

Further chemical modification of Rifamycin SV yielded an improved analog Rifamide, introduced into clinical practice, but was limited to intravenous use. After an extensive modification program, Rifampin was produced, orally available and has become a mainstay of Tuberculosis therapy Lepetit filed for patent protection of Rifamycin B in the UK in August 1958, in the US in March 1959; the British patent GB921045 was granted in March 1963, U. S. Patent 3,150,046 was granted in September 1964; the drug is regarded as having helped conquer the issue of drug-resistant tuberculosis in the 1960s. Rifamycins have been used for the treatment of many diseases, the most important one being HIV-related tuberculosis. A systematic review of clinical trials on alternative regimens for prevention of active tuberculosis in HIV-negative individuals with latent TB found that a weekly, directly observed regimen of rifapentine with isoniazid for three months was as effective as a daily, self-administered regimen of isoniazid for nine months.

But the rifapentine-isoniazid regimen had higher rates of treatment completion and lower rates of hepatotoxicity. However, the rate of treatment-limiting adverse events was higher in the rifapentine-isoniazid regimen; the rifamycins have a unique mechanism of action, selectively inhibiting bacterial DNA-dependent RNA polymerase, show no cross-resistance with other antibiotics in clinical use. However, despite their activity against bacteria resistant to other antibiotics, the rifamycins themselves suffer from a rather high frequency of resistance; because of this and other rifamycins are used in combination with other antibacterial drugs. This is practiced in TB therapy and serves to prevent the formation of mutants that are resistant to any of the drugs in the combination. Rifampin kills fast-dividing bacilli strains as well as “persisters” cells, which remain biologically inactive for long periods of time that allow them to evade antibiotic activity. In addition and rifapentine have both been used against tuberculosis acquired in HIV-positive patients.

Although Tuberculosis therapy remains the most important use of Rifampin, an increasing problem with serious Multiple Drug Resistant bacterial infections has led to some use of antibiotic combinations containing Rifampin to treat them. The antibacterial activity of rifamycins relies on the inhibition of bacterial DNA-dependent RNA synthesis; this is due to the high affinity of rifamycins for the prokaryotic RNA polymerase. The selectivity of the rifamycins depends on the fact that they have a poor affinity for the analogous mammalian enzyme. Crystal structure data of the antibiotic bound to RNA polymerase indicates that rifamycin blocks synthesis by causing strong steric clashes with the growing oligonucleotide. If rifamycin binds the polymerase after the chain extension process has started, no inhibition is observed on the biosynthesis, consistent with a steric-occlusion mechanism. Single step high level resistance to the rifamycins occurs as the result of a single amino acid change in the bacterial DNA dependent RNA polymerase.

The first information on the biosynthesis of the rifamycins came from studies using the stable isotope Carbon-13 and NMR spectroscopy to establish the origin of the carbon skeleton. These studies showed that the ansa chain was derived from acetate and propionate, in common with other polyket

Devonshire Arms

The Devonshire Arms is a moderately common name for an English pub. The name is for the Dukes of members of the peerage from a wealthy aristocratic family. In 2011, the Daily Mail counted 42 pubs with "Devonshire" in their name, ranking it equal to "Five Bells", "Gardeners Arms", "Prince Albert" and "Yew Tree"; the name is for the Dukes of Devonshire, holders of a peerage and members of a wealthy aristocratic family related to the Cavendishes. In areas where they held land, as at Chatsworth, Derbyshire and in Chiswick, there are both Cavendish Arms and Devonshire Arms pubs and street names preserving the names of both families, while at Chatsworth the pub name "The Snake" refers to the family's coat of arms; the Snake Inn, a coaching inn on the old turnpike road on the Snake Pass in the Peak District of Derbyshire gets its name from the Devonshire emblem. The Devonshire Arms in Kensington is a Victorian era pub built in 1865 with a traditional Beer garden, it housed local ARP wardens during The Blitz.

The "Duke of Devonshire" in Balham High Road is a Victorian era corner pub with traditional pub glasswork from the late 1890s, included "an impressive, mirrored bar-back" with original counter and wooden panelling. The mock Tudor Devonshire Arms in Camden known as "The Dev" or by its previous name The Hobgoblin, is said to be "London's most famous alternative venue", it was the first Goth subculture pub in Camden. It is the longest-surviving Goth pub in London and has been a focal point for the city's alternative scene for many years. During the 1980s, Spider Stacy and Shane MacGowan of The Pogues frequented the pub; the interior featured in an episode from a 2003 BBC anthology series, Spine Chillers. The Devonshire Arms in Chiswick's Devonshire Road is a gastropub known as the Manor Tavern; the current building dates from 1924, but a pub existed on the site in 1888. In Skipton, North Yorkshire, the three storey stone-built pub named for the Duke of Devonshire is known as "The Devonshire", it was once called "The New Inn".

In Derbyshire, where the Devonshire / Cavendish family has its great house at Chatsworth, there are Devonshire Arms pubs at Baslow and Pilsley, the last two both on the Chatsworth estate