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Exeter Cathedral

Exeter Cathedral, properly known as the Cathedral Church of Saint Peter in Exeter, is an Anglican cathedral, the seat of the Bishop of Exeter, in the city of Exeter, Devon, in South West England. The present building was complete by about 1400, has several notable features, including an early set of misericords, an astronomical clock and the longest uninterrupted vaulted ceiling in England; the founding of the cathedral at Exeter, dedicated to Saint Peter, dates from 1050, when the seat of the bishop of Devon and Cornwall was transferred from Crediton because of a fear of sea-raids. A Saxon minster existing within the town was used by Leofric as his seat, but services were held out of doors, close to the site of the present cathedral building. In 1107 William Warelwast a nephew of William the Conqueror, was appointed to the see, this was the catalyst for the building of a new cathedral in the Norman style, its official foundation was in 1133, during Warelwast's time, but it took many more years to complete.

Following the appointment of Walter Bronescombe as bishop in 1258, the building was recognised as outmoded, it was rebuilt in the Decorated Gothic style, following the example of Salisbury. However, much of the Norman building was kept, including the two massive square towers and part of the walls, it was constructed of local stone, including Purbeck Marble. The new cathedral was complete by about 1400, apart from the addition of the chapter house and chantry chapels. Like most English cathedrals, Exeter suffered during the Dissolution of the Monasteries, but not as much as it would have done had it been a monastic foundation. Further damage was done during the Civil War. Following the restoration of Charles II, a new pipe organ was built in the cathedral by John Loosemore. Charles II's sister Henrietta Anne of England was baptised here in 1644. During the Victorian era, some refurbishment was carried out by George Gilbert Scott; as a boy, the composer Matthew Locke was trained in the choir of Exeter Cathedral, under Edward Gibbons, the brother of Orlando Gibbons.

His name can be found scribed into the stone organ screen. During the Second World War, Exeter was one of the targets of a German air offensive against British cities of cultural and historical importance, which became known as the "Baedeker Blitz". On 4 May 1942 an early-morning air raid took place over Exeter; the cathedral sustained a direct hit by a large high-explosive bomb on the chapel of St James demolishing it. The muniment room above, three bays of the aisle and two flying buttresses were destroyed in the blast; the medieval wooden screen opposite the chapel was smashed into many pieces by the blast, but it has been reconstructed and restored. Many of the cathedral's most important artefacts, such as the ancient glass, the misericords, the bishop's throne, the Exeter Book, the ancient charters and other precious documents from the library had been removed in anticipation of such an attack; the precious effigy of Walter Branscombe had been protected by sand bags. Subsequent repairs and the clearance of the area around the western end of the building uncovered portions of earlier structures, including remains of the Roman city and of the original Norman cathedral.

Notable features of the interior include the misericords, the minstrels' gallery, the astronomical clock and the organ. Notable architectural features of the interior include the multiribbed ceiling and the compound piers in the nave arcade; the 18-metre-high bishop's throne in the choir was made from Devon oak between 1312 and 1316. The Great East Window contains much 14th-century glass, there are over 400 ceiling bosses, one of which depicts the murder of Thomas Becket; the bosses can be seen at the peak of the vaulted ceiling. Because there is no centre tower, Exeter Cathedral has the longest uninterrupted medieval vaulted ceiling in the world, at about 96 m; the fifty misericords are the earliest complete set in the United Kingdom. They date from two periods: 1220–1230 and 1250–1260. Amongst other things, they depict the earliest known wooden representation of an elephant in the UK, they have supporters. The minstrels' gallery in the nave is unique in English cathedrals, its front is decorated with 12 carved and painted angels playing medieval musical instruments, including the cittern, hautboy, harp, organ, guitar and cymbals, with two others which are uncertain.

Since the above list was compiled in 1921, research among musicologists has revised how some of the instruments are called in modern times. Using revised names, the list should now read from left to right gittern, shawm, harp, jew's harp, organ, recorder, cymbals; the Exeter Cathedral Astronomical Clock is one of the group of famous 14th- to 16th-century astronomical clocks to be found in the West of England. Others are at Wells, Ottery St Mary, Wimborne Minster; the main, dial is the oldest part of the clock, dating from 1484. The fleur-de-lys-tipped hand indicates the hour on a 24-hour analogue dial; the numbering consists of two sets of Roman numerals I to XII. The silver ball and inner dial shows both the age of its phase; the upper dial, added in 1760, shows the minutes. The Latin phrase Pereunt et imputantur, a favourite motto for clocks and sundials, was written by the Latin poet Martial, it is usuall

Richard E. Caves

Richard Earl Caves † was an American economist, Emeritus Professor of Economics at Harvard University. He is known for his work on Multinational enterprises, on industrial organization, on the creative industries, he is known within the motion pictures economics field as the author of a definitive book on the organization of the creative industries titled, Creative Industries: Contracts Between Art and Commerce. Caves obtained his BA in economics at Oberlin College in 1953, he continued his studies at Harvard University, where he obtained his MA in economics in 1956, his PhD in 1958. In 1957, Caves started his academic career at the University of California, Berkeley in the department of Joe S. Bain. In 1962 he moved back to Harvard University, where he was appointed Professor of Economics and lectured in industrial organization and international trade, he served as Department Chairman from 1966 to 1969 and Chairman of the Ph. D in Business Economics from 1984 to 1997, was the George Gund Professor of Economics and Business Administration from 1986 to 1997, subsequently the Nathaniel Ropes Research Professor of Political Economy, from 1997 on.

He retired at Harvard in 2003, became Emeritus Professor of Economics. He sat on the editorial board of the Review of Economics and Statistics from 1992 to 1996. Caves has acted as a Consultant on various topics to various bodies, he was an adviser on international monetary problems for the US Council of Economic Advisers in 1961, deputy to the Special Assistant to the President on foreign trade policy in the same year. From 1963-4 he was a member of the Review Committee for Balance of Payments Statistics at the US Bureau of the Budget. In 1964 he was a member of the White House Task Force on Foreign Economic Policy. From 1972-3 he acted as a consultant to the Council of Ontario Universities, from 1975-6 he was a consultant to the Royal Commission on Corporate Concentration. Caves specializes in industrial and political economics, having authored several books on industrial efficiency and competition. Using this background, Caves provides new insight into the economics of the artistic and creative endeavor.

In his book, Creative Industries: Contracts Between Art and Commerce, Caves looks at the visual and performing arts and television, sound recordings, book publishing, toys and games to investigate how the theory of contracts and the logic of economic organization affect the production of "simple creative goods" and more "complex goods" like plays or motion pictures, which require teams of artists with diverse talents. Under Caves' scrutiny, art collectors and moviegoers are consumers. Sociologist Paul DiMaggio commented that the book: promises to be a much-needed touchstone for work in cultural economics, the sociology of art and culture, the interdisciplinary field of arts and cultural policy analysis.:: Wells Prize, Harvard University, 1957–8 Ford Foundation Faculty Research Fellowship, 1959–60 Gerard C. Henderson Prize, Harvard Law School, 1966 Fellow, American Academy of Arts and Sciences, 1968 Galbraith Prize, 1976, 1981 Kenan Enterprise Award, 1990 Doctor of Economic Science, University of London, 1999 Eminent Scholar, Academy of International Business, 1999 Distinguished Scholar Award, Academy of International Business, 1998 Doctor of Economic Science, University of London, 1999 Distinguished Fellow, Industrial Organization Society, 2001.

Caves, Richard E. Multinational enterprise and economic analysis. Cambridge University Press, 1996. Caves, Richard E. Creative industries: Contracts between art and commerce. Harvard University Press, 2000. Articles, a selection: Caves, Richard E. "International corporations: The industrial economics of foreign investment." Economica: 1-27. Caves, Richard E. "Multinational firms and productivity in host-country markets." Economica: 176-193. Caves, Richard E. and Michael E. Porter. "From entry barriers to mobility barriers: Conjectural decisions and contrived deterrence to new competition*." The Quarterly Journal of Economics: 241-261. Caves, Richard E. "Industrial organization and new findings on the turnover and mobility of firms." Journal of economic literature: 1947-1982

Nanopore sequencing

Nanopore sequencing is a third generation approach used in the sequencing of biopolymers- polynucleotides in the form of DNA or RNA. Using nanopore sequencing, a single molecule of DNA or RNA can be sequenced without the need for PCR amplification or chemical labeling of the sample. At least one of these aforementioned steps is necessary in the procedure of any developed sequencing approach. Nanopore sequencing has the potential to offer low-cost genotyping, high mobility for testing, rapid processing of samples with the ability to display results in real-time. Publications on the method outline its use in rapid identification of viral pathogens, monitoring ebola, environmental monitoring, food safety monitoring, human genome sequencing, plant genome sequencing, monitoring of antibiotic resistance and other applications. Nanopore sequencing uses electrophoresis to transport an unknown sample through an orifice of 10−9 meters in diameter. A nanopore system always contains an electrolytic solution- when a constant electric field is applied, an electric current can be observed in the system.

The magnitude of the electric current density across a nanopore surface depends on the nanopore's dimensions and the composition of DNA or RNA, occupying the nanopore. Sequencing is made possible because, when close enough to nanopores, samples cause characteristic changes in electric current density across nanopore surfaces; the total charge flowing through a nanopore channel is equal to the surface integral of electric current density flux across the nanopore unit normal surfaces between times t1 and t2. Biological nanopore sequencing relies on the use of transmembrane proteins, called porins, that are embedded in lipid membranes so as to create size dependent porous surfaces- with nanometer scale "holes" distributed across the membranes. Sufficiently low translocation velocity can be attained through the incorporation of various proteins that facilitate the movement of DNA or RNA through the pores of the lipid membranes. Alpha hemolysin, a nanopore from bacteria that causes lysis of red blood cells, has been studied for over 15 years.

To this point, studies have shown that all four bases can be identified using ionic current measured across the αHL pore. The structure of αHL is advantageous to identify specific bases moving through the pore; the αHL pore is ~10 nm long, with two distinct 5 nm sections. The upper section consists of a larger, vestibule-like structure and the lower section consists of three possible recognition sites, is able to discriminate between each base. Sequencing using αHL has been developed through basic study and structural mutations, moving towards the sequencing of long reads. Protein mutation of αHL has improved the detection abilities of the pore; the next proposed step is to bind an exonuclease onto the αHL pore. The enzyme would periodically cleave single bases. Coupling an exonuclease to the biological pore would slow the translocation of the DNA through the pore, increase the accuracy of data acquisition. Notably, theorists have shown that sequencing via exonuclease enzymes as described here is not feasible.

This is due to diffusion related effects imposing a limit on the capture probability of each nucleotide as it is cleaved. This results in a significant probability that a nucleotide is either not captured before it diffuses into the bulk or captured out of order, therefore is not properly sequenced by the nanopore, leading to insertion and deletion errors. Therefore, major changes are needed to this method. A recent study has pointed to the ability of αHL to detect nucleotides at two separate sites in the lower half of the pore; the R1 and R2 sites enable each base to be monitored twice as it moves through the pore, creating 16 different measurable ionic current values instead of 4. This method improves upon the single read through the nanopore by doubling the sites that the sequence is read per nanopore. Mycobacterium smegmatis porin A is the second biological nanopore being investigated for DNA sequencing; the MspA pore has been identified as a potential improvement over αHL due to a more favorable structure.

The pore is described as a goblet with a thick rim and a diameter of 1.2 nm at the bottom of the pore. A natural MspA, while favorable for DNA sequencing because of shape and diameter, has a negative core that prohibited single stranded DNA translocation; the natural nanopore was modified to improve translocation by replacing three negatively charged aspartic acids with neutral asparagines. The electric current detection of nucleotides across the membrane has been shown to be tenfold more specific than αHL for identifying bases. Utilizing this improved specificity, a group at the University of Washington has proposed using double stranded DNA between each single stranded molecule to hold the base in the reading section of the pore; the dsDNA would halt the base in the correct section of the pore and enable identification of the nucleotide. A recent grant has been awarded to a collaboration from UC Santa Cruz, the University of Washington, Northeastern University to improve the base recognition of MspA using phi29 polymerase in conjunction with the pore.

Solid state nanopore sequencing approaches, unlike biological nanopore sequencing, do not incorporate proteins into their systems. Instead, solid state nanopore technology uses various metal or metal alloy substrates with nanometer sized pores that allow DNA or RNA to pass through; these substrates most serve integral roles in the sequence recognition of nucleic acids as they translocate through the channels along the substrates. Measurement of electron tunneling