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Mazer (drinking vessel)

A mazer is a special type of wooden drinking vessel, a wide cup or shallow bowl without handles, with a broad flat foot and a knob or boss in the centre of the inside, known technically as the "print" or "boss". Mazers vary from simple pieces all in wood to those ornamented with metalwork, often in silver or silver-gilt. They use dense impervious woods such as maple ("mazer" is an obsolete name for the maple tree), beech and walnut. They represent a north European medieval tradition, and mostly date from the 11th (or earlier) to the 16th centuries.

Etymology
A form of the word mazer may have existed in Old English, but the evidence for this is slight. (The Oxford English Dictionary records speculation, for example, that the word occurs in the place-name Maserfield whose etymology is, however, uncertain.) The modern English word instead derived from Middle English mazer (and its variant spellings); this word was borrowed from Anglo-Norman, a dialect of Old French. Middle English or Anglo-Norman also gave the word to Welsh, as masarn ('maple, sycamore') and dysgl masarn ('mazer bowl').

The Old French word mazre and its variants in turn derive from German, and it is clear that the word must have existed in Common Germanic, where it can be reconstructed as *masuraz. In the West Germanic languages it is found as Old Saxon masur ('swelling') and Old High German masar ('knot or swelling of a tree'), and later in the Middle Ages as Middle Dutch māser ('knot or swelling of a tree', especially a maple), Middle Low German māser ('curly-grained wood'), Middle High German maser ('curly-grained wood, excrescence on the maple and other trees, drinking cup made of curly-grained wood'). In the North Germanic languages it appears as Old Icelandic mǫsurr ('maple tree, veined wood') — including in the form mǫsurr skál ('maplewood vessel') — and Swedish masur ('curly-grained wood').

The Germanic word *masuraz is thought to share its base with Old High German māsa ('spot, scar') and English measles, a base which may also have influenced the word maple. Whether this word has cognates elsewhere in the Indo-European languages is, however, uncertain.

Description
The examples that have been preserved above ground are generally of the most expensive kind, with large mounts in silver, but some archaeological sites have produced quantities of plain wood mazers, which were no doubt the most common at the time. The wreck of the Mary Rose is one example of a group find, and the Nanteos Cup a single survival. They are typically between five and eleven inches in diameter.

Ornamented types usually have a rim or "band" of precious metal, generally of silver or silver gilt; the foot and the print being also of metal. There are examples with wooden covers, sometimes with a metal handle, such as the Bute Mazer or Flemish and German mazers in the British Museum. On the outside, but generally not the inside of the metal band there is often an inscription, religious, or convivial, and the print was also often decorated with a sculpted or engraved plare, and sometimes a gem. The Bute Mazer is one of the most elaborate to survive, with a three-dimensional reclining lion rising from the base, and enamelled coats of arms in a circle around it. Saints, the religious monogram IHS, and animals, often no doubt with heraldic significance, are other common decorations of the boss. Many metal pieces that appear to be mazer bosses have been excavated. An example from York Minster grants an indulgence of 40 days remission from Purgatory for all who drink from it.

Later examples may be raised on a stem, perhaps copying the style of covered cups; some from about 1550 onwards are effectively tazzas that are partly in wood. The later mazers sometimes had metal straps between the rim and the foot, as were added to the Bute Mazer. Examples continued to be produced after the main period ended in the 16th century, perhaps with a deliberate sense of traditionalism. Some modern woodturners and silversmiths have continued to produce examples, especially Omar Ramsden.

Mounted examples are turned very finely, often from burr maple from the field maple. Both the wood and the vessels made of it were known as "mazer", so in contemporary accounts sometimes they are referred to as ciphis de mazer (drinking bowl of burr maple wood), and sometimes simply as a "mazer". The best mazers had silver or silver gilt rims added. Commonly prints were also added (a decorated disc in the base of the bowl), and occasionally, normally on later mazers, a silver or gilt foot was also added.

Use
The size of wooden mazers was restricted by the relatively small size of the trees that gave the best dense and grained wood. The addition of a metal band might double the capacity of a mazer. Large ornamented mazers were probably passed around the table for toasts and the like, as some covered cups were, but more ordinary ones may have been regarded as personal within a group such as a household, ship or monastery, with the finer examples likely being reserved for the leading figures. Evidence from inventories suggests many mazers were given names.

A record of customs at a monastic community in Durham records that each monk has his own mazer "edged with silver double gilt", but also an especially large one called the "Grace cup" was passed around the table after Grace. Another such, called the "Judas cup", was only ever used on Maundy Thursday. Parish churches might be bequeathed mazers, and use them at "church ales" and other parish occasions. Decorated mazers are often included and briefly described in wills and inventories. In 1395 John de Scardeburgh, rector of Tichmarsh, left twelve mazers, two more than were recorded in an inventory of the treasure of Henry IV of England four years later. But monastic inventories could include dozens, including an exceptional 132 in an inventory of 1328 at Christ Church, Canterbury.

In inventories, normally in medieval Latin, they are called by a variety of names (all the plural forms): "ciphi or cuppae de mazero or de murra, mazeri, cyphi murrae, mazerei, or hanaps de mazer (French).

Surviving examples
Over 60 British medieval mazers are known to survive. Many of the English survivals were preserved in Oxbridge colleges, livery companies, hospitals and other institutions going back to the Middle Ages. Relatively few have been passed down in wealthy families, though all such at the time would have owned them; the Bute Mazer is an exception here. A mazer still belonging to All Souls College, Oxford, but on loan to the Ashmolean Museum, was donated to the college in 1437, at the time of its foundation by Thomas Ballard, a landowner in Kent.

Another example in a college is the late 14th-century Swan Mazer of Corpus Christi College, Cambridge, where a swan surmounts a thin column rising from the boss. If the mazer is filled too full, liquid runs down the column and out of the foot, no doubt a trick played on unwary first-timers dining at the college.

Over the late Middle Ages there is a movement from deep bowls with narrow rims to shallower bowls and much wider rims. In the 13th and 14th century rims tend to be simple and plain, only about 1 cm deep without lettering, 15th and 16th century rims are very characteristic with a very deep (3–4 cm moulded form) often with lettering. One exception to this rule is the mazer which Samuel Pepys drank from in 1660 (on display in the British Museum), the rim of this mazer is hallmarked 1507/8 but it is of the earlier simple form. A good display is at the Museum of Canterbury, where ten 13th and 14th century mazers are shown.

A very fine example in the British Museum, from France or Flanders, probably in the early 15th century, has a very thin wooden bowl, and silver mountings of excellent quality, including enamels, but neither the cup nor the cover have metal on the rim, or ever seem to have done so. The cuir-bouilli travelling-case also survives.

The Watson Mazer is the earliest in the sequence of Scottish standing mazers, featuring the coat of arms for David Watson of Saughton. Chemical analysis places it in the early 16th century. It is constructed of a maplewood bowl with a silver-gilt band, resting on a silver stem and an inscribed trumpet-shaped foot. Possibly the work of Adam Leys, today it is part of the Silver Treasury, level 5 of the Scotland Galleries in Edinburgh.

title: Mazer (drinking vessel)


text:
Terzanelle

A terzanelle is a poetic form combining aspects of the villanelle and the terza rima. It is nineteen lines total, with five triplets and a concluding quatrain. The middle line of each triplet stanza is repeated as the third line of the following stanza, and the first and third lines of the initial stanza are the second and final lines of the concluding quatrain; thus, seven of the lines are repeated in the poem. The rhyme scheme and stanzaic structure are as follows (a capitalized letter indicates a line repeated verbatim):
 * A1BA2
 * bCB
 * cDC
 * dED
 * eFE
 * fA1FA2

Or, for the alternate (couplet) ending, the final stanza is:
 * fFA1A2

Notable examples

 * Terzanelle in Thunderweather by Lewis Turco, with a further explanation of the form

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: Terzanelle


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USCGC Mackinaw (WAGB-83)

USCGC Mackinaw (WAGB-83) is a decommissioned United States Coast Guard icebreaker which operated on the Great Lakes for 62 years. A state-of-the-art icebreaker when she was launched in 1944, Mackinaw was built to extend the shipping season on the Great Lakes into the winter months and thereby strengthen the wartime economy of the United States during World War II. Unlike the U.S. Coast Guard's large icebreakers before and since, Mackinaw was designed specifically for use in the shallow, freshwater Great Lakes.

Mackinaw was homeported in Cheboygan, Michigan for her entire Coast Guard career, travelling as needed into Lakes Superior, Huron, Michigan and Erie during icebreaking season to keep shipping lanes and harbors open. After her decommissioning in 2006 in the face of high operating costs, she sailed to a permanent berth in Mackinaw City, Michigan to become the Icebreaker Mackinaw Maritime Museum.

The decommissioned Mackinaw was immediately replaced by a smaller multipurpose Coast Guard cutter, also named Mackinaw (USCGC Mackinaw (WLBB-30)) and also homeported in Cheboygan.

Construction
In the fall of 1941, the United States briefly borrowed the Soviet icebreaker Krassin. Although attempts to lease the icebreaker from the USSR for a year fell through, she was studied by the Coast Guard and her design influenced that of the Coast Guard icebreakers, including Mackinaw, constructed at that time. Another influence was Lieutenant Commander Edward Thiele, USCG, who travelled to Europe on vacation just before the United States entered the war and informed himself of modern icebreaker designs, particularly that of the state-of-the-art Swedish Ymer. Finally, the icebreaking features of Great Lakes rail ferries which operated in heavy ice in the Straits of Mackinac were studied. The resulting preliminary design of the Mackinaw was by the Coast Guard Naval Engineering Division and the final design by naval architects Gibbs & Cox of New York. Gibbs & Cox set up a special icebreaker design section for the Mackinaw and the Wind class of icebreakers.

The Mackinaw was laid down on March 20, 1943, at Toledo Shipbuilding Company in Toledo, Ohio. The Toledo Shipbuilding Company was unprepared to undertake a shipbuilding project this large and complex and when the ship remained incomplete more than two years after the company took on the project, the Toledo Shipbuilding Company went bankrupt due to penalties levied for the delayed construction. The American Ship Building Company took over and Mackinaw was side-launched on March 4, 1944, and commissioned on December 20, 1944 under the command of Commander Edwin J. Roland. Due to war efforts Toledo area male workers were at an all-time low. The shipyard opened their hiring to Toledo area women. They initially hired 12 'helpers' within a short time and eventually hired over 100 women workers. Mackinaw's eventual cost was $10 million, a substantial overrun of her projected cost of $8M and a very high cost for a ship of that era.

Mackinaw's design is based on the Wind class of icebreakers, but she is built specifically for use on the Great Lakes. She was built longer and wider than the ocean-going Wind-class vessels so that she would draw less water in the comparatively shallow water of the Great Lakes. The cooling system which circulates fresh water through her diesel engines draws directly from the water surrounding the ship. She is constructed of mild steel rather than the high-tensile steel of the Wind class.

However, Mackinaw's design shares many characteristics with that of the Wind-class icebreakers, such as a relatively short length in proportion to the great engine power developed, a cut-away forefoot, rounded bottom, and fore, aft and side heeling tanks. Diesel electric machinery was chosen for its controllability and resistance to damage. Although the original blueprints of the Mackinaw called for a length of 300 ft, in the event she was built with a length of 290 ft.

The Mackinaw's double hull is very strong. The frames between the two hulls are spaced about 16 inches apart and form a truss. Voids between the inner and outer hull are filled with fuel tanks and ballast tanks. Water can be pumped rapidly into and out of the ballast tanks (160 tons in 90 seconds) so that the ship heels from side to side through an arc of 24 degrees; this pushes ice away from the sides of the ship. The ballast tanks can also be used to trim the ship fore and aft.

As well as her twin 14 ft stern propellers, Mackinaw also has a 12 ft bow propeller, which pulled water from underneath the ice ahead of the ship; when the Mackinaw rode her bow up onto the ice using her cut-away forefoot, the unsupported ice broke apart under the ship's weight into the hollow space underneath. The turbulent wash from the bow propeller also helped the hull slide through the ice around it. Mackinaw could break through up to 42 in of solid "blue" ice and up to 38 to 40 ft of shattered, heaped-up "windrow" ice. The sides of her hull are protected by an "ice belt" of 1.625 in steel plating up to several feet above her waterline, while her bottom is armored with 1.375 in steel.

Each of the three propellers has its own Westinghouse DC electric motor. The motor driving the bow propeller is capable of 3300 hp and those driving the stern propellors can produce 5000 hp each. These motors are driven by six diesel generator sets, each set comprising a Fairbanks-Morse 38D8-1/8 diesel engine and an accompanying electrical generator. The electrical output of the six generator sets can be switched to the three electric motors in different combinations. When breaking ice, two generators can be assigned to each of the two aft propellers and two generators to the bow propeller. When cruising in open water, each of Mackinaw's aft propellers can be driven by one, two or three generators.

For ground tackle Mackinaw shipped two 6000 lb stockless bower anchors, each with 90 fathom of chain composed of 2 in links. Until they were removed in 1982, two twelve-ton cranes on the fantail could be used to handle seaplanes or buoys. Mackinaw was also equipped to supply fuel oil to remote lighthouses.

Service history
The Mackinaw was constructed to extend the shipping season on the Great Lakes during World War II. Ice formation on the Lakes caused the shipping season to end in late December, not able to reopen until the ice melted in late March or early April. Prior to the war, the light icebreakers USCGC Escanaba and USCGC Tahoma had worked to keep the shipping lanes open in winter, but once the U.S. entered the war these two cutters were reassigned to the north Atlantic. The Coast Guard calculated that extending the shipping season by ten days in winter would allow the delivery of an additional three and a half million tons of iron ore, coal and limestone to the steel industry, or alternatively of 120 million bushels of grain to food markets.

1945-1960
The Mackinaw's first assignment after she was launched in the final winter of World War II was to train 25 Soviet sailors from January 20 to February 6, 1945, before the sailors took up engineering duties on a lend-lease Wind class icebreaker. After the war ended Mackinaw continued on icebreaking duty in the Great Lakes; at that time, the channels between the Great Lakes and the open ocean were not yet large enough to accommodate her. The Mackinaw was then the largest member of a collection of icebreaking Coast Guard cutters on the Great Lakes which also included 180-foot buoy tenders and 110-foot tugboats. During the late 1970s and through the 1980s the latter were replaced by 140-foot Bay-class tugboats. Starting in 1968 and continuing until the last was decommissioned in 1989, one or another of the Coast Guard's Wind-class icebreakers would help out in winter. The Mackinaw and these other Coast Guard icebreakers provided safe passage for freighters as they delivered their cargo of taconite, grain, and other resources around the Great Lakes to ports such as Detroit, Chicago, and Gary.

Mackinaw's icebreaking season each year depended on that winter's ice accumulation on the Great Lakes but typically lasted about 70 days. The season generally began in mid-December and continued until warming weather in spring melted the lake ice, which might be as late as May. A month-long "Charlie period" starting in mid-February took the ship out of service for recovery by both ship and crew from the round-the-clock stresses of icebreaking.

During the icebreaking season the Mackinaw maintained shipping lanes through the ice in Whitefish Bay at the eastern end of Lake Superior, along the St. Marys River connecting Lakes Superior and Huron, and through the Straits of Mackinac connecting Lakes Huron and Michigan. She occasionally cleared ice on the Detroit and St. Clair rivers connecting Lakes Huron and Erie. In very severe winters she visited icebound ports on the lower Great Lakes as far away as Buffalo on eastern Lake Erie. Wherever she went, Mackinaw broke the ice around any trapped ships that she encountered and escorted them to open water.

In the spring of 1947, the Mackinaw and the USCGC Tupelo opened ice-clogged Buffalo harbor. Working from May 9 to 14, they freed 38 ships trapped in ice outside the harbor and escorted them in, and freed 49 ships trapped inside the harbor and led them out. Mackinaw returned the next spring with the USCGC Acacia and during March 17 and 18 broke a passage into the ice-locked harbor which allowed 12 ships to leave. This was the earliest known date in over 50 years that ships had been able to leave Buffalo Harbor in the spring. Mackinaw returned to Buffalo again in April 1961 to lead Tupelo and the Coast Guard tugboats USCGC Kaw and Ojibwa in escorting vessels in and out of the ice-clogged harbor.

The Mackinaw did not routinely perform search and rescue missions; these were normally carried out by smaller, faster, nimbler Coast Guard cutters, boats and aircraft. The Mackinaw's first large search and rescue mission was not until the disappearance of Northwest Orient Airlines Flight 2501 over Lake Michigan on the night of 23 June 1950. Mackinaw, along with other Coast Guard and Navy ships and state police forces, fruitlessly searched for survivors and instead collected airplane debris and human body parts from a wide swath of Lake Michigan. "It was horrible," said David Kaplan, a boatswain's mate on the Mackinaw. "We picked up 32 buckets of remains and stored them in the walk-in cooler until the medical examiner came and took them. We found a lady's purse that looked intact until we opened it. The glass in the small make-up mirror was pulverized."

Mackinaw's powerful engines made her useful for towing large vessels in distress, starting when she towed the U.S. Navy minesweeper USS Elusive into Detroit in late February 1945. Mackinaw had been escorting Elusive through the ice from Lorain to Chicago when the minesweeper's propeller was damaged by ice in Lake Erie.

On November 21, 1956 the 7,300-ton grain carrier J. P. Wells was caught in a storm packing 65 mph winds on Lake Superior. Her rudder was damaged and the freighter began sailing in circles. The Mackinaw cancelled plans to invite the families of the crew to a Thanksgiving dinner onboard and sailed to assist the freighter. Mackinaw, accompanied by the USCGC Mesquite, towed the J. P. Wells to Whiskey Bay in Lake Superior, 15 miles north of the Soo Locks, where the freighter anchored waiting for a commercial tug to tow her to Sault Ste. Marie for repairs. Thanksgiving was celebrated underway.

During the construction of the Mackinac Bridge from 1954 to 1957, the Mackinaw would clear away ice floes piling up against the massive caissons surrounding the bridge piers being constructed. This allowed the foundations of the bridge to settle into place undisturbed during the winter. The icebreaker would work all day around the caissons for several days at a time, anchoring nearby at night and resuming work the next morning.

1960-1990
On the afternoon of November 29, 1960, the freighter SS Francisco Morazan ran aground in a snowstorm off South Manitou Island in Lake Michigan. The Mackinaw arrived to help the next morning, joining USCGC Mesquite which was already on scene. A ship's boat from Mackinaw was able to take off the wife of the Morazan's captain, who was airlifted from Mackinaw to Traverse City. On December 1, the USCGC Sundew, the salvage tug John Roan V, and the tug's companion barge Maintland joined the rescue effort.

The Sundew and Mesquite departed that night. On the following day a salvage engineer and an insurance agent sent by Morazan's owners from New York, along with salvage engineers from Roan Salvage of Sturgeon Bay, were airlifted to Morazan. After evaluating the ship's condition, they concluded was that although the cargo could be salvaged, Morazan could not, and the Roan Salvage engineers departed. Meanwhile, the weather deteriorated until at times fifteen-foot waves were breaking over Morazan and the ship began to break up. On December 4 ship's boats from Mackinaw took the captain, his twelve-man crew and the two owner's representatives off Morazan and Mackinaw delivered them to Traverse City.

On May 10, 1965 Mackinaw was on-scene commander of the Coast Guard's rescue efforts after the Norwegian ship MV Topdalsfjord collided with and sank the U.S. bulk carrier SS Cedarville near the Mackinac Bridge. Mackinaw's crew pulled bodies from the water and took on the survivors of the Cedarville from the German MV Weissenberg which had rescued them.

On November 19, 1966 the German freighter MV Nordmeer grounded and sank in shallow water seven miles north of Thunder Bay Island in Lake Huron. The Mackinaw sailed from Cheboygan, collected 35 members of the crew and the ship's dog and carried them to Alpena either on the 20th or 21st. Nordmeer's captain and seven crewmen stayed on board to plan a salvage operation. A week later, a gale struck the Nordmeer with 50 mph winds and 22-foot seas. The salvage crew radioed for help on November 29 and the Mackinaw returned to the vicinity, but the weather and the Nordmeer's position on Thunder Bay Shoal made it impossible for the icebreaker to approach the stricken freighter. A Coast Guard helicopter co-piloted by Lieutenant Jack Rittichier flew from Detroit and airlifted the eight crewmen to Mackinaw. The Nordmeer broke apart soon afterward.

In 1967, the Mackinaw travelled through the Welland Canal and visited Montreal to attend the Expo 67 International and Universal Exposition. This trip incidentally demonstrated that because of the expansion of the Saint Lawrence Seaway over the years, Mackinaw was no longer restricted to the Great Lakes, although the design of her power plant still restricted her to fresh water. She visited Toronto in July 1986 and in 2002.

Early on December 8, 1976, the ore carrier Cliffs Victory was forced out of her channel on the Saint Marys River by a sudden surge of current-driven ice and  ran aground. After some of the Cliffs Victory's cargo was unloaded into a barge, the Mackinaw tried unsuccessfully all the next day to pull the ore carrier off the submerged shoal on which she was grounded. Cliffs Victory remained aground until the early morning of 11 December, when Mackinaw and three tugboats freed her from the shoal. In the meantime, more than 60 other ships had lined up waiting for the river to be cleared, including six ocean-going freighters hurrying to reach the St. Lawrence Seaway before it closed on the 18th. This was the worst shipping jam on the Saint Marys River since 1926.

The 1984 Great Lakes navigation season officially opened on March 26 but as commercial shipping began to move through the Lakes, unexpected winds drove ice from Lake Huron into the St. Clair River, blocking the river from April 5 to 29. The St. Clair connects Lake Erie and the Saint Lawrence Seaway with Lake Huron and the other Great Lakes. The consequent ice jam set records for both its economic impact and its lateness in the icebreaking season.

Six cargo ships were driven ashore by the ice. Eighteen ships became trapped in a mile-and-a-half stretch of the river. As many as 87 ore carriers and oceangoing freighters waited outside the ice jam, at a total cost estimated at $1.7 million each day.

The Mackinaw sailed from Cheboygan on April 9. Along with four smaller U.S. Coast Guard cutters and the Canadian Coast Guard icebreakers CCGS Des Groseilliers and CCGS Griffon, she led convoys through the ice jam day after day. By the time the ice was dispersed by time and weather, 300 ships had made their way through the congested St. Clair River. Thousands of onlookers watched "the ice jam of the century" from the river banks and amateur radio operators listened to VHF radio traffic among the ships.

1990-2006
In 1991, Mackinaw's first female sailors, both enlisted and officers, began to report aboard following an overhaul to the ship's living quarters. During the summer, the regular female crewmembers made way for female cadets from the Coast Guard Academy.

In 1998, Mackinaw's white hull with the blue and red Coast Guard stripe on the bow was painted red with a white and blue bow stripe. All of the Coast Guard's other full-sized icebreakers had already been repainted from white to red in 1972 and 1973.

The Mackinaw approached the end of her service as she became too expensive to maintain. The Coast Guard had scheduled her for decommissioning in 1982, 1988, and 1994, but cancelled each decommissioning after objections from the shipping industry and Congress. The closing chapter of the icebreaker's service history finally opened in December of 2000, when the Coast Guard called for designs of the ship's replacement. The annual cost of maintaining the ship was a little over US$4 million, and Coast Guard spokesman Jack O'Dell said at that time, "She's extremely old, and she's just becoming impossible to operate. Ships have a life span, and once they've reached that life span, they break down. This one's reached her life span." The Coast Guard chose a design for a combination icebreaker and buoy tender, also to be named Mackinaw.

In the spring of 2004, the Cheboygan City Council sent out feelers to its constituents to see if any group would be willing to take possession of Mackinaw after its projected decommissioning in June 2006 and to keep the ship in the Mackinac Straits area—ideally in Cheybogan. The city did not want to own and maintain the ship itself. In August of that year a committee, the Icebreaker Mackinaw Maritime Museum (IMMM), was formed to develop the ship as a museum. Michigan's congressional delegation was enlisted to help and introduced legislation which directed the Coast Guard to convey Mackinaw to Cheboygan upon decommissioning. Cheboygan, for its part, hoped the legislation would allow the city to immediately transfer the ship to the IMMM.

By the early months of 2006, little progress had been made. The legislation had passed in the U.S. House of Representatives but was stalled in the Senate, and moorings for the proposed museum in Cheboygan had not yet been found. The IMMM began work on a backup plan to host the museum in Mackinaw City, a village 15 miles north of Cheboygan. Mackinaw City's high tourist traffic would improve the museum's financial viability, and a member of the IMMM's board owned suitable moorings there at the former railroad dock for the ferry SS Chief Wawatam. In this alternate plan, the General Services Administration (GSA) would take possession of the ship upon decommissioning (as is usual for decommissioned U.S. government ships) and then transfer it to the IMMM.

In the last days before the Mackinaw's decommissioning on June 10, 2006, this alternate plan was adopted. After 62 years of service, Mackinaw was decommissioned in Cheboygan at a ceremony shared by the commissioning of her successor Coast Guard icebreaker, the new Mackinaw. On June 21, the decommissioned Mackinaw, loaded with civilian passengers, sailed to Mackinaw City and moored at her permanent berth. On June 30, after briefing the IMMM on how to operate the moored ship, the Coast Guard crew departed and the IMMM took over from the GSA as Mackinaw's custodians; full title to the ship was to be transferred from the GSA to the IMMM 60 months later. The Icebreaker Mackinaw Maritime Museum received its first visitors in the tourist season of 2007.

Unrelated history
Tragically, the Mackinaw was unavailable on November 10, 1975, when the SS Arthur M. Anderson and SS Edmund Fitzgerald made their fateful journey across Lake Superior, where the Fitzgerald sank with all 29 crew members aboard 15 miles from Whitefish Point. Whether or not the Mackinaw aided the Anderson and other vessels in the futile search for survivors is unknown.

As museum ship

The Icebreaker Mackinaw Maritime Museum is moored at the eastern end of the old SS Chief Wawatam railroad dock; entry to the area is just south of Shepler's Marine Service. The museum provides educational tours and overnight stays on the vessel. Visitors can tour the mess deck, the captain's quarters, bridge, engine room, wardroom, sick bay and other areas. A retail store on the vessel sells relevant products. A fee is charged to visitors but all current and former USCG personnel are admitted free upon presentation of proper identification.

Amateur radio
The Charlevoix, Cheboygan, Emmet Counties Public Service Communications Organization (CCECPSCO), has established a full-time amateur radio station on board the Icebreaker Mackinaw Maritime Museum.

The CCECPSCO has two repeaters on Mackinaw to provide communications coverage throughout the Straits of Mackinac. These repeaters, operating under the call-sign W8AGB to match the ship's WAGB-83 designation, are on a radio frequency of 145.110 MHz with 103.5 Hz PL tone and 444.375 MHz with 107.2 Hz PL tone. The organization is also actively assisting the museum with restoration and operation of various communications, navigation, and power systems. Included with the radios on board the ship are two Sunair RT-9000 HF transceivers with matching antenna couplers and vertical antennas. The installation of a third RT-9000 paired with an LPA-9600 solid-state kilowatt amplifier and CU-9100 kilowatt autotuner was scheduled for spring 2010, along with a Sunair F-9800 automatic pre/post filter for each radio to permit simultaneous operation of all three stations, and Sunair RCU-9310 remote control panels.

The vessel is equipped with a 160-40 meter dipole antenna, antenna couplers and vertical antennas linked to the two Sunair RT-9000 transceivers. The CCECPSCO group planned to add extra antennae for VHF and UHF repeater use and a KC8TU customized wire antenna.

Amateur radio operators visiting Mackinaw may operate the W8AGB station whenever a CCECPSCO member is present. The CCECPSCO conducts Amateur Radio Field Day operations from Mackinaw on the fourth full weekend in June.

Awards

 * American Campaign Medal -
 * World War II Victory Medal -
 * National Defense Service Medal with three service stars -
 * Global War on Terrorism Service Medal -

title: USCGC Mackinaw (WAGB-83)


text: User talk:65.30.43.103

title: User talk:65.30.43.103


text:
Karyn Parsons

Karyn Parsons Rockwell (born October 8, 1966) is an American actress, author and comedian. She is best known for her role as Hilary Banks on the NBC sitcom The Fresh Prince of Bel-Air from 1990 to 1996. Parsons also starred in the 1995 film Major Payne opposite Damon Wayans, and in The Job (2001–2002) as Toni.

Early life
Parsons was born on October 8, 1966, in Los Angeles, California. In an interview for Essence in 2008, she described her parentage as biracial. Her mother, Louise (Hankerson) Parsons, was an African-American from Charleston, South Carolina, and her father, Kenneth B. Parsons, was of English and Welsh descent, from Butte, Montana. She attended Santa Monica High School.

Career
Parsons starred as Hilary Banks on the sitcom The Fresh Prince of Bel-Air, which aired on NBC from 1990 to 1996. She co-created, co-produced, co-wrote, and co-starred on the Fox sitcom Lush Life in 1996, which was later canceled after four episodes. In 2001, she starred in the critically acclaimed but short-lived television series The Job with Denis Leary. Besides television, Parsons has starred in several films, particularly in comedies such as Late Nights (1992), Major Payne (1995), and The Ladies Man (2000). Parsons is the founder of the Sweet Blackberry Foundation, which produces animated films and books about unsung black heroes. The first video in the series was about Henry Box Brown, a slave who mailed himself to freedom.

Parsons has also published three books for children: a middle-grade novel, How High the Moon (2019), which was loosely inspired by stories of her mother's childhood in the Jim Crow South; and two Sweet Blackberry picture-book biographies about black historical figures, illustrated by R. Gregory Christie: Flying Free (2020) about pioneering aviator Bessie Coleman, and Saving the Day (2021) about inventor Garrett Morgan.

Personal life
Parsons married director Alexandre Rockwell in 2003. Together they have a daughter, Lana, and a son, Nico.

title: Karyn Parsons


text:
User talk:Pmarkham

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 * Remember to use a neutral point of view!
 * If you need any help, feel free to post a question at the Help Desk
 * Explore, be bold in editing pages, and, most importantly, have fun!

Also, here are some odds and ends that I find useful from time to time:

 * Policy Library
 * Utilities
 * Cite your sources
 * Verifiability
 * Wikiquette
 * Civility
 * Conflict resolution
 * Brilliant prose
 * Pages needing attention
 * Peer review
 * Bad jokes and other deleted nonsense
 * Village pump
 * Boilerplate text

Feel free to ask me anything the links and talk pages don't answer. You can most easily reach me by posting on my talk page.

You can sign your name on any page by typing 4 tildes, likes this: ~~~~.

Best of luck, and have fun!

ClockworkSoul 05:14, 28 Feb 2005 (UTC)

Ship pronouns
Please do not change these without discussing it prior to making the change. The proper place to suggest blanket changes to multiple articles would be at Wikipedia talk:WikiProject Ships. Thanks, -MBK004 04:36, 27 September 2008 (UTC)
 * Absolutely bring it up at WT:SHIPS, because we don't go by what someone wants, we go by our own consensus, which in some cases you are blatantly violating when you change an article that already uses the pronouns a certain way. There actually is a clause in the MilMOS about this and since everything on wikipedia is based on consensus, I absolutely recommend discussing this before you continue at all on the pronoun issue. -MBK004 20:42, 15 October 2008 (UTC)

ArbCom elections are now open!
MediaWiki message delivery (talk) 12:49, 23 November 2015 (UTC)

title: User talk:Pmarkham


text:
Roque González y de Santa Cruz

Roque González de Santa Cruz, SJ (17 November 1576 – 15 November 1628) was a Jesuit priest who was the first missionary among the Guarani people in Paraguay. He is honored as a martyr and saint by the Catholic Church.

Life
González was born in the city of Asunción, now part of Paraguay, on 17 November 1576. He was the son of the Spanish colonists Bartolomé González y de Villaverde and María de Santa Cruz, who were both from noble families. Due to the large native population in the region, he spoke Guaraní fluently from an early age, as well as his native Spanish.

In 1598, at the age of 23, González was ordained a priest by Fernando Trexo y Senabria, the Bishop of Córdoba, to serve that diocese. In 1609 he became a member of the Society of Jesus, beginning his work as a missionary in what is now Brazil. He became the first European person to enter the region known today as the State of Rio Grande do Sul, extending the system of Jesuit reductions begun in Paraguay to that region.

González' arrival in the area happened only after his developing delicate relationships of trust with local indigenous leaders, some of whom feared that the priests were preparing the way for the arrival of masses of Spanish colonists in their land.

In 1613 González led the founding of the Reduction of San Ignacio Miní. In 1615 he founded Itapúa, which is now the City of Posadas in the Argentine Province of Misiones. Then he had to move the reduction to the other side of the river, now the site of the City of Encarnación. He also founded the reductions of Concepción de la Sierra Candelaria (1619), Candelaria (1627), San Javier, Yapeyú (now in the Province of Corrientes), San Nicolás, Asunción del Ijuí, and Caaró (now in Brazil). In the region of Iyuí, he had difficulties with the local chieftain and sorcerer (cacique) Nheçu (written Ñezú in Spanish), who opposed the missions.

On 15 November 1628, while preparing to oversee the installation of a new bell for the church at the Mission of Todos los Santos de Caaró, González was struck down and killed with a tomahawk, along with his fellow Jesuit, Juan del Castillo, upon the orders of Nheçu. After their deaths, their bodies were dragged into the church, which was set ablaze. Two days later, their colleague Alonso Rodríguez y Olmedo was also murdered by followers of Nheçu.

Veneration
González was beatified by Pope Pius XI on 28 January 1934. He and his companions were later canonized by Pope John Paul II in Asunción, thus becoming the first native of Paraguay to be declared a saint by the Catholic Church.

González has been named the patron saint of the cities of Posadas, Argentina, and Encarnación, Paraguay. Liturgically he is commemorated on 16 November, along with the other "Martyrs of the Rio de la Plata".

title: Roque González y de Santa Cruz


text:
Roque Gonzales, Rio Grande do Sul

Roque Gonzales is a municipality located in the northwestern region of the southernmost state of Rio Grande do Sul, Brazil, east of the Uruguay River and the Argentinian border. Roque Gonzales was named after the jesuit missionary and saint Roque González de Santa Cruz.

The municipality would be partially flooded by the proposed Garabí Dam.

Neighboring municipalities

 * Porto Xavier
 * São Paulo das Missões
 * São Pedro do Butiá
 * Rolador
 * São Luiz Gonzaga
 * Dezesseis de Novembro
 * Pirapó

History
Primarily German-Brazilians or Deutschbrasilianer from the old colonized areas of the state of Rio Grande do Sul settled Roque Gonzales. The original German settlements whence they came were often referred to as Altkolonie because they are located on the eastern part of the state where Germans first put down roots, starting in 1824 (i.e. Estrela, Montenegro, Lajeado, etc.).

East Pomeranian has been spoken in Esquina Emanuel since the early days of its foundation because it was settled by immigrants of Pomeranian descent. Dona Otília was settled primarily by Lutherans. Typically most of the German speakers in the municipality and in the wider region spoke Riograndenser Hunsrückisch and identified with the Roman Catholic tradition and customs. In 2012 the state chamber of deputies voted unanimously in favor of recognizing this Germanic dialect an official historical culture good to be preserved.

The city of Roque Gonzales is home of writer Nelson Hoffmann who wrote, among other works, Eu vivo só ternuras which was translated into Italian as Io vivo di tenerezze by Marco Scalabrino. The book is about the relationship of a grandfather, the author, with his first grandson. It has received positive reviews and has been classified by some as a book for all ages.

The Premio Missões of literature of Roque Gonzales is headed by João Weber Griebeler of Igaçaba Produções Culturais and it covers mostly Brazilian literature but some works in other languages are also occasionally published (collective anthology). Griebeler also is the editor of the local newspaper, the Jornal Igaçaba.

Roque Gonzales is located near the margins of the Rio Ijuí. Not too far south from the town the river turns into a wide waterfall: Salto Pirapó. Camping is available in the area. It is a great place for bird watching, hiking a relaxation. This is also the location of a small hydroelectric plant built almost one hundred years ago and a fixture in local history. Two new hydroelectric plants have been built on the Ijuí river within the general region.

title: Roque Gonzales, Rio Grande do Sul


text:
Sarah Tisdall

Sarah Caroline Tisdall (born 1960 in Plymouth) is a former Foreign & Commonwealth Office (FCO) clerical officer who was jailed for leaking British government documents to a newspaper in 1983.

In 1983, the UK government agreed to base nuclear armed cruise missiles in the UK. The decision was controversial and defence minister Michael Heseltine and Prime Minister Margaret Thatcher wanted to keep the missiles' arrival date a secret to minimise potential demonstrations. Tisdall anonymously sent The Guardian photocopied documents detailing when the missiles would be arriving in Britain. The documents set out the political tactics Heseltine would use to present the matter in the House of Commons.

The Government brought a legal action against The Guardian, seeking an order requiring the newspaper to reveal its source. Although The Guardian successfully argued that it was protected by section 10 of the Contempt of Court Act 1981 from providing the information, the decision by Mr Justice Scott was almost immediately overturned. The appeal by the Attorney General was on the grounds that although the documents themselves were harmless, a civil servant capable of leaking them might leak other documents which could pose a threat to national security.

The editor of the Guardian, Peter Preston, was prepared to defy the court order and go to prison, but was advised that it was more likely that a fine would be imposed on the newspaper, increasing as long as refusal persisted. This could potentially bankrupt the paper. Defying the order would also violate the Guardian's policy that the law should be obeyed. A meeting of Guardian journalists was held, in a mood that was, according to David McKie, deputy editor at the time, troubled but sympathetic rather than outraged.

After the meeting Preston complied with the court order to hand over the documents—which he described as the worst day of his 20-year editorship—and immediately submitted his resignation, which was not accepted. The documents were identified as coming from an FCO photocopying machine, which led to Tisdall. In March 1984, Tisdall pleaded guilty to a charge under section 2 of the Official Secrets Act 1911. She was sentenced to six months in prison, and released after four months.

The legality of the Order (compelling The Guardian to surrender the documents, and thus reveal their source) was upheld in a decision of the House of Lords (Secretary of State for Defence v. Guardian Newspapers Ltd. [1985] AC 339) by a majority of three against two.

As of 2005, Tisdall worked for an ethical property company developing accommodation for charitable organisations and community groups.

title: Sarah Tisdall


text:
File:Million Dollar Baby poster.jpg

Summary
Poster for Million Dollar Baby. Obtained from.

Fair use in Million Dollar Baby
Though this image is subject to copyright, its use is covered by the U.S. fair use laws because:
 * 1) It's a low resolution copy of a Film Poster / VHS or DVD Cover.
 * 2) It doesn't limit the copyright owner's rights to sell the film in any way, in fact, it may encourage sales.
 * 3) Because of the low resolution, copies could not be used to make illegal copies of the artwork/image.
 * 4) The image is itself a subject of discussion in the article or used in the infobox thereof.
 * 5) The image  is significant because it was used to promoted a notable film.

Source

 * 1) Derived from a digital capture (photo/scan) of the Film Poster/ VHS or DVD Cover (creator of this digital version is irrelevant as the copyright in all equivalent images is still held by the same party). Copyright held by the film company or the artist.  Claimed as fair use regardless.

Fair use rationale for use in American films of 2004

 * 1) For an article covering the films released in the USA in 2004, one original poster identifying the Academy Award winning film of that year in the absence of any other images significantly contribrutes to the article and illustrates the role and significance of that film in cinemtatic history.
 * 2) No free or public domain images have been located for this film or indeed any films of that year.
 * 3) The image is of lower resolution than the original poster (copies made from it will be of inferior quality).
 * 4) The poster is being used for informational purposes only, and its use is not believed to detract from the original film or affect the copyright holder in any way. The poster's use in that film history article is entirely encyclopedic in nature and is believed to enhance an understanding of film in  that year in history.
 * 5) The poster is used on various websites, and its use on Wikipedia does not make it significantly more accessible than it already is.

Fair use in Hilary Swank
Though this image is subject to copyright, its use is covered by the U.S. fair use laws because:
 * 1) It's a low resolution copy of a Film Poster / VHS or DVD Cover.
 * 2) It doesn't limit the copyright owner's rights to sell the film in any way, in fact, it may encourage sales.
 * 3) Because of the low resolution, copies could not be used to make illegal copies of the artwork/image.
 * 4) The image is itself a subject of discussion in the article or used in the infobox thereof.
 * 5) The image  is significant because it was used to promoted a notable film.

title: File:Million Dollar Baby poster.jpg


text:
Arroyo Hondo

Arroyo Hondo (Spanish: deep stream) may refer to:

United States

 * Arroyo Hondo (Santa Clara County, California), a stream
 * Arroyo Hondo, Santa Fe County, New Mexico, a census-designated place
 * Arroyo Hondo, Taos County, New Mexico, a census-designated place
 * Arroyo Hondo Pueblo in New Mexico
 * Hondo Creek, Texas; site of the 1842 Battle of Arroyo Hondo

Other nations

 * Arroyohondo, a municipality in Colombia
 * Arroyo Hondo, Cuba, a settlement in Guantánamo municipality

title: Arroyo Hondo


text:
Wikipedia:Featured picture candidates/Bison skull pile, ca1870.png

Bison skull pile
I recently saw this photo on a documentary and immediately thought of W:FPC. It is an enormous pile of bison skulls waiting to be ground for fertilizer, in the 1870s. The way the photo was presented in the documentary involved a slow zoom-out from the man at the top to reveal the entire pile-- it definitely fits the criteria of striking/shocking/impressive. The photo demonstrates the extensive slaughter of the bison: from around 60 million in 1800 to as few as 750 in 1890.

Unfortunately, the largest version of this photo on the internet is not very large, and it doesn't appear to be available in any books for scanning. So, I will present the best that I could find, cleaned up as much as possible. It is currently featured in the article American bison, which appears to be the only article that talks about the slaughter of the bison. --brian0918™ 05:26, 28 Feb 2005 (UTC)
 * Nominate and support. --brian0918™ 05:26, 28 Feb 2005 (UTC)
 * Support for impact. Dear god, what have we done? – ClockworkSoul 05:28, 28 Feb 2005 (UTC)
 * I've attempted to clean it up further, others are welcome to do the same. --brian0918™ 05:40, 28 Feb 2005 (UTC)
 * Support. -- Chris 73 Talk 07:08, Feb 28, 2005 (UTC)
 * Support, great example of a striking, shocking image. Mgm|(talk) 10:28, Feb 28, 2005 (UTC)
 * Support, fits the criteria for Featured Pic perfectly - Adrian Pingstone 10:35, 28 Feb 2005 (UTC)
 * Support Junes 13:47, 28 Feb 2005 (UTC)
 * Support. It's very easy to click through articles on endangered species and shrug, but this stops you in your tracks.  And good job on the touchup. —Korath (Talk) 12:12, Mar 1, 2005 (UTC)
 * Support. -- AllyUnion (talk) 03:01, 3 Mar 2005 (UTC)
 * Support. I seem to recall that Pol Pot built similar mounds of skulls in Cambodia, although he didn't use bison. -- Solipsist 22:46, 5 Mar 2005 (UTC)
 * Support. Very odd picture, but I like it.  →mathx314(talk)(email) 20:07, 6 Mar 2005 (UTC)
 * Support. Very striking! Kitanzi 22:51, 10 Mar 2005 (UTC)
 * Support- gives a person a good feel for the full extent of the slaughter; it really drives the point home. TomStar81 06:12, 11 Mar 2005 (UTC)
 * Whoa. Definitely support. - Vague | Rant 13:27, Mar 13, 2005 (UTC)
 * Promoted. +13/-0 -- BRIAN 0918  17:13, 15 Mar 2005 (UTC)


text: Category:Geography of Iraq

title: Category:Geography of Iraq


text: User talk:128.194.68.199

title: User talk:128.194.68.199


text:
P-glycoprotein

P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein of the cell membrane that pumps many foreign substances out of cells. More formally, it is an ATP-dependent efflux pump with broad substrate specificity. It exists in animals, fungi, and bacteria, and it likely evolved as a defense mechanism against harmful substances.

P-gp is extensively distributed and expressed in the intestinal epithelium where it pumps xenobiotics (such as toxins or drugs) back into the intestinal lumen, in liver cells where it pumps them into bile ducts, in the cells of the proximal tubule of the kidney where it pumps them into urinary filtrate (in the proximal tubule), and in the capillary endothelial cells composing the blood–brain barrier and blood–testis barrier, where it pumps them back into the capillaries.

P-gp is a glycoprotein that in humans is encoded by the ABCB1 gene. P-gp is a well-characterized ABC-transporter (which transports a wide variety of substrates across extra- and intracellular membranes) of the MDR/TAP subfamily. The normal excretion of xenobiotics back into the gut lumen by P-gp pharmacokinetically reduces the efficacy of some pharmaceutical drugs (which are said to be P-gp substrates). In addition, some cancer cells also express large amounts of P-gp, further amplifying that effect and rendering these cancers multidrug resistant. Many drugs inhibit P-gp, typically incidentally rather than as their main mechanism of action; some foods do as well. Any such substance can sometimes be called a P-gp inhibitor.

P-gp was discovered in 1971 by Victor Ling.

Gene
A 2015 review of polymorphisms in ABCB1 found that "the effect of ABCB1 variation on P-glycoprotein expression (messenger RNA and protein expression) and/or activity in various tissues (e.g. the liver, gut and heart) appears to be small. Although polymorphisms and haplotypes of ABCB1 have been associated with alterations in drug disposition and drug response, including adverse events with various ABCB1 substrates in different ethnic populations, the results have been majorly conflicting, with limited clinical relevance."

Protein
P-gp is a 170 kDa transmembrane glycoprotein, which includes 10–15 kDa of N-terminal glycosylation. The N-terminal half of the protein contains six transmembrane helixes, followed by a large cytoplasmic domain with an ATP-binding site, and then a second section with six transmembrane helixes and an ATP-binding domain that shows over 65% of amino acid similarity with the first half of the polypeptide. In 2009, the first structure of a mammalian P-glycoprotein was solved (3G5U). The structure was derived from the mouse MDR3 gene product heterologously expressed in Pichia pastoris yeast. The structure of mouse P-gp is similar to structures of the bacterial ABC transporter MsbA (3B5W and 3B5X) that adopt an inward facing conformation that is believed to be important for binding substrate along the inner leaflet of the membrane. Additional structures (3G60 and 3G61) of P-gp were also solved revealing the binding site(s) of two different cyclic peptide substrate/inhibitors. The promiscuous binding pocket of P-gp is lined with aromatic amino acid side chains.

Through Molecular Dynamic (MD) simulations, this sequence was proved to have a direct impact in the transporter's structural stability (in the nucleotide-binding domains) and defining a lower boundary for the internal drug-binding pocket.

Species, tissue, and subcellular distribution
P-gp is expressed primarily in certain cell types in the liver, pancreas, kidney, colon, and jejunum. P-gp is also found in brain capillary endothelial cells.

Function
Substrate enters P-gp either from an opening within the inner leaflet of the membrane or from an opening at the cytoplasmic side of the protein. ATP binds at the cytoplasmic side of the protein. Following binding of each, ATP hydrolysis shifts the substrate into a position to be excreted from the cell. Release of the phosphate (from the original ATP molecule) occurs concurrently with substrate excretion. ADP is released, and a new molecule of ATP binds to the secondary ATP-binding site. Hydrolysis and release of ADP and a phosphate molecule resets the protein, so that the process can start again.

The protein belongs to the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. P-gp is an ATP-dependent drug efflux pump for xenobiotic compounds with broad substrate specificity. It is responsible for decreased drug accumulation in multidrug-resistant cells and often mediates the development of resistance to anticancer drugs. This protein also functions as a transporter in the blood–brain barrier. Mutations in this gene are associated with colchicine resistance and Inflammatory bowel disease 13. Alternative splicing and the use of alternative promoters results in multiple transcript variants.

P-gp transports various substrates across the cell membrane including:

 * Drugs such as colchicine, desloratadine, tacrolimus and quinidine.
 * Chemotherapeutic agents such as topoisomerase inhibitors (i.e. etoposide, doxorubicin), microtubule-targeted drugs (i.e. vinblastine), and tyrosine kinase inhibitors (i.e. gefitinib, sunitinib).
 * Lipids
 * Steroids
 * Xenobiotics
 * Peptides
 * Bilirubin
 * Cardiac glycosides like digoxin
 * Immunosuppressive agents
 * Glucocorticoids like dexamethasone
 * HIV-type 1 antiretroviral therapy agents like protease inhibitors and nonnucleoside reverse transcriptase inhibitors

Its ability to transport the above substrates accounts for the many roles of P-gp including:

 * Regulating the distribution and bioavailability of drugs
 * Increased intestinal expression of P-glycoprotein can reduce the absorption of drugs that are substrates for P-glycoprotein. Thus, there is a reduced bioavailability, and therapeutic plasma concentrations are not attained. On the other hand, supratherapeutic plasma concentrations and drug toxicity may result because of decreased P-glycoprotein expression
 * Active cellular transport of antineoplastics resulting in multidrug resistance to these drugs
 * The removal of toxic metabolites and xenobiotics from cells into urine, bile, and the intestinal lumen
 * The transport of compounds out of the brain across the blood–brain barrier
 * Digoxin uptake
 * Prevention of ivermectin and loperamide entry into the central nervous system
 * The migration of dendritic cells
 * Protection of hematopoietic stem cells from toxins.

It is inhibited by many drugs, such as amiodarone, azithromycin, captopril, clarithromycin, cyclosporine, piperine, quercetin, quinidine, quinine, reserpine, ritonavir, tariquidar, and verapamil.

Regulation of expression and function of P-gp in cancer cells
At the transcriptional level, the expression of P-gp has been intensively studied, and numerous transcription factors and pathways are known to play roles. A variety of transcription factors, such as p53, YB-1, and NF-κB are involved in the direct regulation of P-gp by binding to the promoter regions of the P-gp gene. Many cell signaling pathways are also involved in transcriptional regulation of P-gp. For example, the PI3K/Akt pathway and the Wnt/β-catenin pathway were reported to positively regulate the expression of P-gp. Mitogen-activated protein kinase (MAPK) signaling includes three pathways: the classical MAPK/ERK pathway, the p38 MAPK pathway, and the c-Jun N-terminal kinase (JNK) pathway, all of which were reported to have implications in the regulation of the expression of P-gp. Studies suggested that the MAPK/ERK pathway is involved in the positive regulation of P-gp; the p38 MAPK pathway negatively regulates the expression of the P-gp gene; and the JNK pathway was reported to be involved in both positive regulation and negative regulation of P-gp.

After 2008, microRNAs (miRNAs) were identified as new players in regulating the expression of P-gp in both transcriptional and post-transcriptional levels. Some miRNAs decrease the expression of P-gp. For example, miR-200c down-regulates the expression of P-gp through the JNK signaling pathway or ZEB1 and ZEB2; miR-145 down-regulates the mRNA of P-gp by directly binding to the 3'-UTR of the gene of P-gp and thus suppresses the translation of P-gp. Some other miRNAs increase the expression of P-gp. For example, miR-27a up-regulates P-gp expression by suppressing the Raf kinase inhibitor protein (RKIP); alternatively, miR-27a can also directly bind to the promoter of the P-gp gene, which works in a similar way with the mechanism of action of transcriptional factors.

The expression of P-gp is also regulated by post-translational events, such as post-transcriptional modification, degradation, and intracellular trafficking of P-gp. Pim-1 protects P-gp from ubiquitination and the following degradation in the proteasome. Small GTPases Rab5 down-regulates the endocytotic trafficking of P-gp and thus increases the functional P-gp level on the cell membrane; while Small GTPases Rab4 work in an opposite way: Rab4 down-regulates the exocytotic trafficking of P-gp from intracellular compartments to the cell membrane, and therefore decreases the functional P-gp level on the cell membrane.

Drug interactions
Some common pharmacological inhibitors of P-glycoprotein include: amiodarone, clarithromycin, ciclosporin, colchicine, diltiazem, erythromycin, felodipine, ketoconazole, lansoprazole, omeprazole and other proton-pump inhibitors, nifedipine, paroxetine, reserpine, saquinavir, sertraline, quinidine, tamoxifen, verapamil, and duloxetine. Elacridar and CP 100356 are other common P-gp inhibitors. Zosuquidar and tariquidar were also developed with this in mind. Lastly, valspodar and reversan are other examples of such agents. ABCB1 is linked to the daily dose of warfarin required to maintain the INR to a target of 2.5. Patients with the GT or TT genotypes of the 2677G>T SNP require around 20% more warfarin daily.

Common pharmacological inducers of P-glycoprotein include carbamazepine, dexamethasone, doxorubicin, nefazodone, phenobarbital, phenytoin, prazosin, rifampicin, St. John's wort, tenofovir, tipranavir, trazodone, and vinblastine.

Substrates of P-glycoprotein are susceptible to changes in pharmacokinetics due to drug interactions with P-gp inhibitors or inducers. Some of these substrates include colchicine, ciclosporin, dabigatran, digoxin, diltiazem, fexofenadine, indinavir, morphine, and sirolimus.

Diseases (non-cancer)
Decreased P-gp expression has been found in Alzheimer's disease brains.

Altered P-gp function has also been linked to inflammatory bowel diseases (IBD); however, due to its ambivalent effects in intestinal inflammation many questions remain so far unanswered. While decreased efflux activity may promote disease susceptibility and drug toxicity, increased efflux activity may confer resistance to therapeutic drugs in IBD. Mice deficient in MDR1A develop chronic intestinal inflammation spontaneously, which appears to resemble human ulcerative colitis.

Cancer
P-gp efflux activity is capable of lowering intracellular concentrations of otherwise beneficial compounds, such as chemotherapeutics and other medications, to sub-therapeutic levels. Consequently, P-gp overexpression is one of the main mechanisms behind decreased intracellular drug accumulation and development of multidrug resistance in human multidrug-resistant (MDR) cancers.

History
P-gp was first characterized in 1976. P-gp was shown to be responsible for conferring multidrug resistance upon mutant cultured cancer cells that had developed resistance to cytotoxic drugs.

The structure of mouse P-gp, which has 87% sequence identity to human P-gp, was resolved by x-ray crystallography in 2009. The first structure of human P-gp was solved in 2018, with the protein in its ATP-bound, outward-facing conformation.

Research
Radioactive verapamil can be used for measuring P-gp function with positron emission tomography.

P-gp is also used to differentiate transitional B cells from naive B cells. Dyes such as rhodamine 123 and MitoTracker dyes from Invitrogen can be used to make this differentiation.

MDR1 as a drug target
It has been suggested that MDR1 inhibitors might treat various diseases, especially cancers, but none have done well in clinical trials.

Single nucleotide polymorphism rs1045642
Single Nucleotide Polymorphism rs1045642 (3435T>C or 3435C>T) is important for the differential activity of the P-gp pump.

Homozygous subjects, identified with the TT genotype, are usually more able to extrude xenobiotics from the cell. A Homozygous genotype for the allele ABCB1/MDR1 is capable of a higher absorption from the blood vessels and a lower extrusion into the lumen. Xenobiotics are extruded at a lower rate with heterozygous (CT) alleles compared to homozygous ones.

title: P-glycoprotein


text:
User:Sxesteve0

Profile pending...

title: User:Sxesteve0


text:
Hohne

Hohne is a municipality in the state of Lower Saxony in Germany, east of the county town of Celle. It includes the three former parishes of Hohne, Helmerkamp and Spechtshorn. It should not be confused with the British Army camp of Hohne (German: Lager Bergen-Hohne) near Belsen about 30 km to the northwest.

Geography
Hohne lies on the River Wiehe, a right-hand tributary of the Schwarzwasser, which itself flows into the River Aller near Schwachhausen.

History
The Hohne Village History Society (Arbeitskreis Hohner Dorfgeschichte) has researched all records on individual villages in the area and has discovered the earliest record of the place: on Ascension Day in 1313 Bere de Hone inherited the fief of a farm at Hohne from the St. Aegidien Monastery in Brunswick. This monastery was founded before 1115 by Margravine Gertrud von Braunschweig of Meissen, last heiress of the Brunonen family.

Religion
The majority of inhabitants in Hohne are Lutheran Protestants and belong to the parish of the Church of the Ascension (Himmelfahrtskirche). Also in the parish of Hohne are the villages of Helmerkamp, Hahnenhorn, Spechtshorn, Pollhöfen and Ummern.

Shield
A plough or, share and cutter argent in a fesse vert, on a chief or a cock courant sable, crested and wattled gules

Notable buildings
The ploughed-over ruins of a motte and bailey (Turmhügelburg) are situated north of Hohne on the Glindmoor towards Hohnhorst, in a field on the Hohne Manor estate (Rittergut Hohne). It was probably an earth mound on which a wooden tower formerly stood. To date only wooden remains have been found.

These structures were built across Europe from western France to present-day eastern Poland in the 9th and 10th centuries, sometimes even as late as the early 13th century. One archaeologist has suggested that it could be part of a defensive network extending outwards from Beedenbostel. More detailed research into the age of the palisade stakes that have been found on the site has not yet been possible due to financial constraints. As a result it can only be surmised that the castle was built before AD 995, perhaps together with the stone tower in Beedenbostel or at the same time as the Mundburg. The Mundburg itself was built by the old confluence of the rivers Aller and Oker near Wienhausen.

The present-day 18th century Hohne Manor is partly built on the walls of the old castle that the young robber baron from Gifhorn, Hendrik von Veltheim, is believed to have destroyed on 11 July 1372 during the Lüneburg succession conflict. Areas of cobbles and large stone fragments of old foundations can still be found 0.7 m under the present-day surface of the land (were embankments levelled out here?), which suggests that a small castle originally stood here. As at Hesleburg castle near Heeßel, and the castles of Depenau and Dachtmissen on the Aue in Flotwedel, the terrain was then wetter than today and inaccessible from Grethegau to the north. In the 20th century part of the building was moved to other locations in the estate.

The 1913 neo-romanesque Church of the Ascension (Himmelfahrtskirche) in Hohne inherited the altar, organ, pulpit and font of its predecessor church.

Hohne is also home to the "Hohne Ice House" (Hohner Kalthaus), which is run by one of the oldest ice house societies in Lower Saxony, the Kalthausgemeinschaft Hohne von 1955 e. V., on behalf of the village.

Education
There is a primary school (catchment area: Ahnsbeck, Helmerkamp, Hohne, Spechtshorn) and a public library (Schulweg 1).

Since 1970 the German Red Cross has run Hohne kindergarten.

Educational trips are organised by the Hohne Countrywoman's Society (LandFrauenverein Hohne).

Sport
The sports club, TuS Hohne/Spechtshorn, is involved in various ball sports, track and field athletics, and judo, especially youth sports.

The Hohne/Spechtshorn Woodland Swimming Pool Society (Förderverein Waldbad Hohne/Spechtshorn) looks after the woodland swimming pool (the Waldbad), which is mainly used for youth sport. Youth swimming passes can be bought from the local branch of the German Lifeguard Association (Deutsche Lebens-Rettungs-Gesellschaft).

There are two shooting clubs: the Hohne Shooting Club (Schützengilde Hohne von 1708 e. V.) and the Spechtshorn Shooting Club (Schießgruppe Spechtshorn von 1978 e. V.)

Regular events

 * The Hohne Shooting Club organises an annual shooting fair; the 2008 champion shot is Arne Heinrich, the youth champion is Yannik Müller.
 * The Hohne Village History Society (Arbeitskreis Hohner Dorfgeschichte) has been putting together the village history since 2002 under the direction of Rainer Brammer. - The first two volumes were presented in 2006 at a well-attended event in the Church of the Ascension.

Public services
The equal rights representatives of the Lachendorf municipal association (Angela Barkus, Rathaus Lachendorf) act as women's representatives.

The Hohne Volunteer Fire Service (Freiwillige Feuerwehr Hohne) is a fire station with specialist roles in breathing equipment and dangerous goods and is part of the Celle district fire brigade.

title: Hohne


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Physical dependence

Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, stimulants, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.

Symptoms
Physical dependence can manifest itself in the appearance of both physical and psychological symptoms which are caused by physiological adaptions in the central nervous system and the brain due to chronic exposure to a substance. Symptoms which may be experienced during withdrawal or reduction in dosage include increased heart rate and/or blood pressure, sweating, and tremors. More serious withdrawal symptoms such as confusion, seizures, and visual hallucinations indicate a serious emergency and the need for immediate medical care. Sedative hypnotic drugs such as alcohol, benzodiazepines, and barbiturates are the only commonly available substances that can be fatal in withdrawal due to their propensity to induce withdrawal convulsions. Abrupt withdrawal from other drugs, such as opioids can cause an extremely painful withdrawal that is very rarely fatal in patients of general good health and with medical treatment, but is more often fatal in patients with weakened cardiovascular systems; toxicity is generally caused by the often-extreme increases in heart rate and blood pressure (which can be treated with clonidine), or due to arrhythmia due to electrolyte imbalance caused by the inability to eat, and constant diarrhea and vomiting (which can be treated with loperamide and ondansetron respectively) associated with acute opioid withdrawal, especially in longer-acting substances where the diarrhea and emesis can continue unabated for weeks, although life-threatening complications are extremely rare, and nearly non-existent with proper medical management.

Treatment
Treatment for physical dependence depends upon the drug being withdrawn and often includes administration of another drug, especially for substances that can be dangerous when abruptly discontinued or when previous attempts have failed. Physical dependence is usually managed by a slow dose reduction over a period of weeks, months or sometimes longer depending on the drug, dose and the individual. A physical dependence on alcohol is often managed with a cross tolerant drug, such as long acting benzodiazepines to manage the alcohol withdrawal symptoms.

Drugs that cause physical dependence

 * All μ-opioids with any (even slight) agonist effect, such as (partial list) morphine, heroin, codeine, oxycodone, buprenorphine, nalbuphine, methadone, and fentanyl, but not agonists specific to non-μ opioid receptors, such as salvinorin A (a k-opioid agonist), nor opioid antagonists or inverse agonists, such as naltrexone (a universal opioid inverse agonist)
 * All GABA agonists and positive allosteric modulators of both the GABA-A ionotropic receptor and GABA-B metabotropic receptor subunits, including (partial list):
 * alcohol (alcoholic beverage) (cf. alcohol dependence, alcohol withdrawal, delirium tremens)
 * barbiturates such as phenobarbital, sodium thiopental and secobarbital
 * benzodiazepines such as diazepam (Valium), lorazepam (Ativan), and alprazolam (Xanax) (see benzodiazepine dependence and benzodiazepine withdrawal syndrome)
 * nonbenzodiazepine hypnotics (z-drugs) such as zopiclone and zolpidem.
 * gamma-hydroxybutyric acid (GHB) and 1,4-butanediol
 * carisoprodol (Soma) and related carbamates (tybamate and meprobamate)
 * baclofen (Lioresal) and its non-chlorinated analogue phenibut
 * chloral hydrate
 * glutethimide
 * clomethiazole
 * methaqualone (Quaalude)
 * nicotine (tobacco) (cf. nicotine withdrawal)
 * gabapentinoids such as gabapentin (Neurontin), pregabalin (Lyrica), and phenibut (Noofen), which are inhibitors of α2δ subunit-containing VDCCs
 * antiepileptic drugs such as valproate, lamotrigine, tiagabine, vigabatrin, carbamazepine and oxcarbazepine, and topiramate
 * antipsychotic drugs such as clozapine, risperidone, olanzapine, haloperidol, thioridazine, etc.
 * commonly prescribed antidepressants such as the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) (cf. SSRI/SNRI withdrawal syndrome)
 * blood pressure medications, including beta blockers such as propanolol and alpha-adrenergic agonists such as clonidine
 * androgenic-anabolic steroids
 * glucocorticoids

Rebound syndrome
A wide range of drugs whilst not causing a true physical dependence can still cause withdrawal symptoms or rebound effects during dosage reduction or especially abrupt or rapid withdrawal. These can include caffeine, stimulants,   steroidal drugs and antiparkinsonian drugs. It is debated whether the entire antipsychotic drug class causes true physical dependency, a subset, or if none do. But, if discontinued too rapidly, it could cause an acute withdrawal syndrome. When talking about illicit drugs rebound withdrawal, especially with stimulants, it is sometimes referred to as "coming down" or "crashing".

Some drugs, like anticonvulsants and antidepressants, describe the drug category and not the mechanism. The individual agents and drug classes in the anticonvulsant drug category act at many different receptors and it is not possible to generalize their potential for physical dependence or incidence or severity of rebound syndrome as a group so they must be looked at individually. Anticonvulsants as a group however are known to cause tolerance to the anti-seizure effect. SSRI drugs, which have an important use as antidepressants, engender a discontinuation syndrome that manifests with physical side effects; e.g., there have been case reports of a discontinuation syndrome with venlafaxine (Effexor).

title: Physical dependence