Paxillus involutus

Paxillus involutus, commonly known as the brown roll-rim, common roll-rim is a basidiomycete fungus that is widely distributed across the Northern Hemisphere. It has been inadvertently introduced to Australia, New Zealand, South Africa, and South America, probably transported in soil with European trees. Various shades of brown in colour, the fruit body grows up to 6 cm (2.4 in) high and has a funnel-shaped cap up to 12 cm (5 in) wide with a distinctive inrolled rim and decurrent gills that may be pore-like close to the stipe. Although it has gills, it is more closely related to the pored boletes than to typical gilled mushrooms. It was first described by Pierre Bulliard in 1785, and was given its current binomial name by Elias Magnus Fries in 1838. Genetic testing suggests that "Paxillus involutus" may be a species complex rather than a single species.
A common mushroom of deciduous and coniferous woods and grassy areas in late summer and autumn, "Paxillus involutus" forms ectomycorrhizal relationships with a broad range of tree species. These benefit from the symbiosis as the fungus reduces their intake of heavy metals and increases resistance to pathogens such as "Fusarium oxysporum". Previously considered edible and eaten widely in Eastern and Central Europe, it has since been found to be dangerously poisonous, after being responsible for the death of German mycologist Julius Schäffer in 1944. It had been recognized as causing gastric upsets when eaten raw, but was more recently found to cause potentially fatal autoimmune hemolysis, even in those who had consumed the mushroom for years without any other ill effects. An antigen in the mushroom triggers the immune system to attack red blood cells. Serious and commonly fatal complications include acute kidney injury, shock, acute respiratory failure, and disseminated intravascular coagulation.
Taxonomy and naming.
The brown roll-rim was described by French mycologist Pierre Bulliard in 1785 as "Agaricus contiguus", although the 1786 combination "Agaricus involutus" of August Batsch is taken as the first valid description. James Bolton published a description of what he called "Agaricus adscendibus" in 1788; the taxonomical authority Index Fungorum considers this to be synonymous with "P. involutus". Additional synonyms include "Omphalia involuta" described by Samuel Frederick Gray in 1821, and "Rhymovis involuta", published by Gottlob Ludwig Rabenhorst in 1844. The species gained its current binomial name in 1838 when the 'father of mycology', Swedish naturalist Elias Magnus Fries erected the genus "Paxillus", and set it as the type species. The starting date of fungal taxonomy had been set as January 1, 1821, to coincide with the date of Fries' works, which meant that names coined earlier than this date required sanction by Fries (indicated in the name by a colon) to be considered valid. It was thus written "Paxillus involutus" (Batsch:Fr.) Fr. A 1987 revision of the International Code of Botanical Nomenclature set the starting date at May 1, 1753, the date of publication of Linnaeus' seminal work, the "Species Plantarum". Hence the name no longer requires the ratification of Fries' authority.
The genus was later placed in a new family, Paxillaceae, by French mycologist René Maire who held it to be related to both agarics and boletes. Although it has gills rather than pores, it has long been recognised as belonging to the pored mushrooms of the order Boletales rather than the traditional agarics. The generic name is derived from the Latin for 'peg' or 'plug', and the specific epithet "involutus", 'inrolled', refers to the cap margin. Common names include the naked brimcap, poison paxillus, inrolled pax, poison pax, common roll-rim, brown roll-rim, and brown chanterelle. Gray called it the "involved navel-stool" in his 1821 compendium of British flora.
Studies of the ecology and genetics of "Paxillus involutus" indicate that it may form a complex of multiple similar-looking species. In a field study near Uppsala, Sweden, conducted from 1981 to 1983, mycologist Nils Fries found that there were three populations of "P. involutus" unable to breed with each other. One was found under conifers and mixed woodlands, while the other two were found in parklands, associated with nearby birch trees. He found that the first group tended to produce single isolated fruit bodies which had a thinner stipe and cap which was less inrolled at the margins, while the fruit bodies of the other two populations tended to appear in groups, and have thicker stipes, and caps with more inrolled and sometimes undulating margins. There were only general tendencies and he was unable to detect any consistent macroscopic or microscopic features that firmly differentiate them. A molecular study comparing the DNA sequences of specimens of "Paxillus involutus" collected from various habitats in Bavaria found that those collected from parks and gardens showed a close relationship with the North American species "P. vernalis", while those from forests were allied with "P. filamentosus". The authors suggested the park populations may have been introduced from North America. A multi-gene analysis of European isolates showed that "P. involutus" "sensu lato" (in the loose sense) could be separated into four distinct, genetically isolated lineages corresponding to "P. obscurosporus", "P. involutus" "sensu stricto" (in the strict sense), "P. validus", and a fourth species that has not yet been identified. Changes in host range have occurred frequently and independently among strains within this species complex.
Description.
Resembling a brown wooden top, the epigeous (aboveground) fruit body may be up to 6 cm (2.4 in) high. The cap, initially convex then more funnel-shaped (infundibuliform) with a depressed centre and rolled rim (hence the common name), may be reddish-, yellowish- or olive-brown in colour and typically 4–12 cm (1.6–5 in) wide; the cap diameter does not get larger than . The cap surface is initially downy and later smooth, becoming sticky when wet. The cap and cap margin initially serve to protect the gills of young fruit bodies: this is termed pilangiocarpic development. The narrow brownish yellow gills are decurrent and forked, and can be peeled easily from the flesh (as is the case with the pores of boletes). Gills further down toward the stipe become more irregular and anastomose, and can even resemble the pores of bolete-type fungi. The fungus darkens when bruised and older specimens may have darkish patches. The juicy yellowish flesh has a mild to faintly sour or sharp odor and taste, and has been described as well-flavored upon cooking. Of similar colour to the cap, the short stipe can be crooked and tapers toward the base.
The spore print is brown, and the dimensions of the ellipsoid (oval-shaped) spores are 7.5–9 by 5–6 μm.
The hymenium has cystidia both on the gill edge and face (cheilo- and pleurocystidia respectively), which are slender and filament-like, typically measuring 40–65 by 8–10.5 μm.
Similar species.
The brownish colour and funnel-like shape of "P. involutus" can lead to its confusion with several species of "Lactarius", many of which have some degree of toxicity themselves. The lack of a milky exudate distinguishes it from any milk cap. One of the more similar is "L. turpis", which presents a darker olive colouration. The related North American "Paxillus vernalis" has a darker spore print, thicker stipe and is found under aspen, whereas the closer relative "P. filamentosus" is more similar in appearance to "P. involutus". A rare species that grows only in association with alder, "P. filamentosus" can be distinguished from it by the pressed-down scales on the cap surface that point towards the cap margin, a light yellow flesh that bruises only slightly brown, and deep yellow-ochre gills that do not change colour upon injury
The most similar species are two once thought to be part of "P. involutus" in Europe. "Paxillus obscurisporus" (originally "obscurosporus") has larger fruit bodies than "P. involutus", with caps up to wide whose margins tend to unroll and flatten with age, and a layer of cream-coloured mycelia covering the base of its tapered stipe. "P. validus", also known only from Europe, has caps up to wide with a stipe that is more or less equal in width throughout its length. Found under broadleaved trees in parks, it can be reliably distinguished from "P. involutus" (and other "Paxillus" species) by the presence of crystals up to 2.5 μm long in the rhizomorphs, as the crystals found in rhizomorphs of other "Paxillus" species do not exceed 0.5 μm long.
Ecology, distribution and habitat.
"Paxillus involutus" forms ectomycorrhizal relationships with a number of coniferous and deciduous tree species. Because the fungus has somewhat unspecialized nutrient requirements and a relatively broad host specificity, it has been frequently used in research and seedling inoculation programs. There is evidence of the benefit to trees of this arrangement: in one experiment where "P. involutus" was cultivated on the root exudate of red pine ("Pinus resinosa"), the root showed markedly increased resistance to pathogenic strains of the ubiquitous soil fungus "Fusarium oxysporum". Seedlings inoculated with "P. involutus" also showed increased resistance to "Fusarium". Thus "P. involutus" may be producing antifungal compounds which protect the host plants from root rot. "Paxillus involutus" also decreases the uptake of certain toxic elements, acting as a buffer against heavy metal toxicity in the host plant. For example, the fungus decreased the toxicity of cadmium and zinc to Scots pine ("Pinus sylvestris") seedlings: even though cadmium itself inhibits ectomycorrhiza formation in seedlings, colonization with "P. involutus" decreases cadmium and zinc transport to the plant shoots and alters the ratio of zinc transported to the roots and shoots, causing more cadmium to be retained in the roots of the seedlings rather than distributed through its entire metabolism. Evidence suggests that the mechanism for this detoxification involves the cadmium binding to the fungal cell walls, as well as accumulating in the vacuolar compartments. Further, ectomycorrhizal hyphae exposed to copper or cadmium drastically increase production of a metallothionein—a low molecular weight protein that binds metals.
The presence of "Paxillus involutus" is related to much reduced numbers of bacteria associated with the roots of "Pinus sylvestris". Instead bacteria are found on the external mycelium. The types of bacteria change as well; a Finnish study published in 1997 found that bacterial communities under "P. sylvestris" without mycorrhizae metabolised organic and amino acids, while communities among "P. involutus" metabolised the sugar fructose. "Paxillus involutus" benefits from the presence of some species of bacteria in the soil it grows in. As the fungus grows it excretes polyphenols, waste products that are toxic to itself and impede its growth, but these compounds are metabolised by some bacteria, resulting in increased fungal growth. Bacteria also produce certain compounds such as citric and malic acid, which stimulate "P. involutus".
Highly abundant, the brown roll-rim is found across the Northern Hemisphere, Europe and Asia, with records from India, China, Japan, Iran, and Turkey's eastern Anatolia. It is equally widely distributed across northern North America, extending north to Alaska, where it has been collected from tundra near Coldfoot in the interior of the state. In southwestern Greenland, "P. involutus" has been recorded under the birch species "Betula nana", "B. pubescens" and "B. glandulosa". The mushroom is more common in coniferous woods in Europe, but is also closely associated with birch ("Betula pendula"). Within woodland, it prefers wet places or boggy ground, and avoids calcareous (chalky) soils. It has been noted to grow alongside "Boletus badius" in Europe, and "Leccinum scabrum" and "Lactarius plumbeus" in the Pacific Northwest region of North America. There it is found in both deciduous and coniferous woodland, commonly under plantings of white birch ("Betula papyrifera") in urban areas. It is one of a small number of fungal species which thrive in "Pinus radiata" plantations planted outside their natural range. A study of polluted Scots pine forest around Oulu in northern Finland found that "P. involutus" became more abundant in more polluted areas while other species declined. Emissions from pulp mills, fertiliser, heating and traffic were responsible for the pollution, which was measured by sulfur levels in the pine needles.
"Paxillus involutus" can be found growing on lawns and old meadows throughout its distribution. Fruit bodies are generally terrestrial, though they may be found on woody material around tree stumps. They generally appear in autumn and late summer. In California, David Arora discerned a larger form associated with oak and pine which appears in late autumn and winter, as well as the typical form that is associated with birch plantings and appears in autumn. Several species of flies and beetles have been recorded using the fruit bodies to rear their young. The mushroom can be infected by "Hypomyces chrysospermus", or bolete eater, a mould species that parasitises Boletales members. Infection results in the appearance of a whitish powder that first manifests on the pores, then spreads over the surface of the mushroom, becoming golden yellow to reddish-brown in maturity.
Australian mycologist John Burton Cleland noted it occurring under larch ("Larix"), oak, pine, birch and other introduced trees in South Australia in 1934, and it has subsequently been recorded in New South Wales, Victoria (where it was found near "Betula" and "Populus") and Western Australia. It has been recorded under introduced birch ("Betula") and hazel ("Corylus") in New Zealand. Mycologist Rolf Singer reported a similar situation in South America, with the species recorded under introduced trees in Chile. It is likely to have been transported to those countries in the soil of imported European trees.
Toxicity.
"Paxillus involutus" was widely eaten in Central and Eastern Europe until World War II, although English guidebooks did not recommend it. In Poland, the mushroom was often eaten after pickling or salting. It was known to be a gastrointestinal irritant when ingested raw but had been presumed edible after cooking. Questions were first raised about its toxicity after German mycologist Julius Schäffer died after eating it in October 1944. About an hour after he and his wife ate a meal prepared with the mushrooms, Schäffer developed vomiting, diarrhea, and fever. His condition worsened to the point where he was admitted to hospital the following day and developed kidney failure, perishing after 17 days.
In the mid-1980s, Swiss physician René Flammer discovered an antigen within the mushroom that stimulates an autoimmune reaction causing the body's immune cells to consider its own red blood cells as foreign and attack them. Despite this, it was not until 1990 that guidebooks firmly warned against eating "P. involutus", and one Italian guidebook recommended it as edible in 1998. The relatively rare immunohemolytic syndrome occurs following the repeated ingestion of "Paxillus" mushrooms. Most commonly it arises when the person has ingested the mushroom for a long period of time, sometimes for many years, and has shown mild gastrointestinal symptoms on previous occasions. The "Paxillus" syndrome is better classed as a hypersensitivity reaction than a toxicological reaction as it is caused not by a genuinely poisonous substance but by the antigen in the mushroom. The antigen is still of unknown structure but it stimulates the formation of IgG antibodies in the blood serum. In the course of subsequent meals, antigen-antibody complexes are formed; these complexes attach to the surface of blood cells and eventually lead to their breakdown.
Poisoning symptoms are rapid in onset, consisting initially of vomiting, diarrhea, abdominal pain, and associated decreased blood volume. Shortly after these initial symptoms appear, hemolysis develops, resulting in reduced urine output, hemoglobin in the urine or outright absence of urine formation, and anemia. Medical laboratory tests consist of testing for the presence of increasing bilirubin and free hemoglobin, and falling haptoglobins. Hemolysis may lead to numerous complications including acute kidney injury, shock, acute respiratory failure, and disseminated intravascular coagulation. These complications can cause significant morbidity with fatalities having been reported.
There is no antidote for poisoning, only supportive treatment consisting of monitoring complete blood count, renal function, blood pressure, and fluid and electrolyte balance and correcting abnormalities. The use of corticosteroids may be a useful adjunct in treatment, as they protect blood cells against hemolysis, thereby reducing complications. Plasmapheresis reduces the circulating immune complexes in the blood which cause the hemolysis, and may be beneficial in improving the outcome. Additionally, hemodialysis can be used for patients with compromised kidney function or kidney failure.
"Paxillus involutus" also contains agents which appear to damage chromosomes; it is unclear whether these have carcinogenic or mutagenic potential. Two compounds that have been identified are the phenols involutone and involutin; the latter is responsible for the brownish discolouration upon bruising.


Nares Strait

Nares Strait (; ) is a waterway between Ellesmere Island and Greenland that connects the northern part of Baffin Bay in the Atlantic Ocean with the Lincoln Sea in the Arctic Ocean. From south to north, the strait includes Smith Sound, Kane Basin, Kennedy Channel, Hall Basin and Robeson Channel. During 1962–64, a by ice island drifted southward from the Lincoln Sea through the Nares and Davis Straits to the Atlantic Ocean (Labrador Sea). Nares strait has a nearly permanent current from the north, powered by the Beaufort Gyre, making it harder to traverse for ships coming from the south.
In 1964, its name was agreed by the Danish ("Stednavneudvalget", now "Stednavnenævnet") and Canadian governments. The name derives from the British naval officer George Strong Nares.
The strait and neighbouring waters are usually hazardous for navigation and shipping. During August, however, it is usually navigable by icebreakers. Prior to 1948, only five vessels were recorded as having successfully navigated north of Kane Basin. In 2009 the ship "Arctic Sunrise" made the first known June transit into the Arctic Ocean.
Hans Island, a tiny island lying within the strait, is claimed by both Denmark (on behalf of Greenland) and Canada. Other islands within the strait are Joe Island, Crozier Island, and the much larger Franklin Island.
Thule People reached the Nares Strait in the early 13th century, where they hunted with and traded with Vikings. Archeological remains of Thule Culture and Viking presence are found on Ruin Island.


Khaled Hosseini

Khaled Hosseini ( ; ; born 4 March 1965) is an Afghan-American novelist, physician, activist, humanitarian, and UNHCR goodwill ambassador. His debut novel "The Kite Runner" (2003) was a critical and commercial success; the book, as well as his subsequent novels, have all been at least partially set in Afghanistan and has featured an Afghan as the protagonist.
Born in Kabul, Afghanistan, Hosseini's father was a diplomat; after periods living in Iran and France, when Hosseini was 15, his family applied for asylum in the United States, where he later became a naturalised citizen. Hosseini did not return to Afghanistan until 2000 when he was 36, where he likened the experience to feeling "like a tourist in [his] own country". In subsequent interviews, Hosseini has admitted to feeling survivor's guilt for having been able to leave the country prior to the Soviet invasion and subsequent wars.
After graduating from college, Hosseini worked as a physician in California, a situation he likened to "an arranged marriage". The success of "The Kite Runner" meant he was able to retire from medicine in order to write full-time. His three novels have all reached various levels of critical and commercial success. "The Kite Runner" spent 101 weeks on "The New York Times" Best Seller list, including three weeks at number one. His second novel, "A Thousand Splendid Suns" (2007) spent 103 weeks on the chart, including 15 at number one. "And the Mountains Echoed" (2013), his third novel, remained on the chart for 33 weeks. In addition to his writing, Hosseini has become a noted advocate for refugees, including establishing with the UNHCR the Khaled Hosseini Foundation to support Afghan refugees returning to Afghanistan.
Early life and education.
Early life.
Hosseini was born on March 4, 1965 in Kabul, Afghanistan, the eldest of five children. His father, Nasser, worked as a diplomat for the Ministry of Foreign Affairs in Kabul while his mother worked as a Persian language teacher at a girls high school; both originate from Herat. Regarding his ethnicity, Hosseini stated, "I'm not pure anything ... There's a Pashtun part of me, a Tajik part of me." His mother's family is believed to be from the Mohammadzai tribe of Pashtuns. Hosseini describes his upbringing as privileged. He spent eight years of his childhood in the upper class Wazir Akbar Khan neighborhood in Kabul. Hosseini does not recall his sister, Raya, ever suffering discrimination for being a female. Kabul itself was "a growing, thriving, cosmopolitan city" where he regularly flew kites with a number of cousins.
In 1970, Hosseini and his family moved to Iran where his father worked for the Embassy of Afghanistan in Tehran. In 1973, Hosseini's family returned to Kabul, and Hosseini's youngest brother was born in July of that year. In 1976, when Hosseini was 11 years old, his father secured a job in Paris, France, and moved the family there. They were unable to return to Afghanistan because of the April 1978 Saur Revolution in which the People's Democratic Party of Afghanistan (PDPA) seized power. In 1980, shortly after the start of the Soviet–Afghan War, they sought political asylum in the United States and made their residence in San Jose, California. Hosseini, then aged 15, did not speak English when he first arrived in the United States. He describes the experience as "a culture shock" and "very alienating".
Despite their distance from the country's turmoil, the family was aware of the situations faced by a number of their friends and relatives. Hosseini explained:
Education.
Hosseini graduated from Independence High School in San Jose in 1984 and enrolled at Santa Clara University, where he earned a bachelor's degree in biology in 1988. The following year, he entered the University of California San Diego School of Medicine, where he earned his M.D. in 1993. He completed his residency in internal medicine at Cedars-Sinai Medical Center in Los Angeles in 1997. He practiced medicine for over ten years, until a year and a half after the release of "The Kite Runner".
Career.
Novels.
In 2003, Hosseini released his first novel, "The Kite Runner", the story of a young boy, Amir, struggling to establish a closer rapport with his father and coping with memories of a traumatic childhood event. The novel is set in Afghanistan, from the fall of the monarchy until the collapse of the Taliban regime, as well as in the San Francisco Bay Area, specifically in Fremont, California. The novel was the best selling novel of 2005 in the United States, according to Nielsen BookScan. "The Kite Runner" was also produced as an audiobook read by the author. "The Kite Runner" has been adapted into a film of the same name released in December 2007. Hosseini made a cameo appearance towards the end of the movie as a bystander when Amir buys a kite which he later flies with Sohrab.
Hosseini's second novel, "A Thousand Splendid Suns", was published in 2007, and is also set in Afghanistan. The story addresses many of the same issues as Hosseini's first, but from a female perspective. It follows the story of two women, Mariam and Laila, whose lives become entwined when Mariam's husband takes on Laila as a second wife. The story is set during Afghanistan's tumultuous thirty-year transition from Soviet occupation to Taliban control and post-Taliban rebuilding. The novel was released by Riverhead Books on May 22, 2007, at the same time as the Simon & Schuster audiobook. The adaptation rights of the novel were subsequently acquired by producer Scott Rudin and Columbia Pictures.
Hosseini's third novel "And the Mountains Echoed" was released on May 21, 2013. Prior to its release, Hosseini said:
United Nations High Commissioner for Refugees.
Hosseini is currently a Goodwill Envoy for the United Nations High Commissioner for Refugees (UNHCR). He has been working to provide humanitarian assistance in Afghanistan through the Khaled Hosseini Foundation. The concept for the foundation was inspired by the trip to Afghanistan that Hosseini made in 2007 with UNHCR, with the organisation raising funds to build homes for refugees returning to Afghanistan.
In 2018, Hosseini published an illustrated short story, "Sea Prayer", inspired by the death of Alan Kurdi, a three year old refugee who drowned when trying to reach Europe from Syria. Proceeds from sales went to the UNHCR and the Khaled Hosseini Foundation.
Influences.
As a child, Hosseini read a lot of Persian poetry, especially the works of poets such as Rumi, Omar Khayyám, Abdul-Qādir Bēdil, and Hafez. He has also cited a Persian translation of Jack London's "White Fang" as a key influence from his youth, in addition to translations of novels including "Alice in Wonderland" and Mickey Spillane's Mike Hammer series. He has cited Afghan singer Ahmad Zahir as a key musical influence, choosing the songs "Madar' and "Aye Padesha Khuban" as his two Inheritance Tracks during an appearance on BBC Radio 4's Saturday Live, and naming Zahir as "the Afghan Elvis" and stating his music was "one of the seminal memories of my time in Afghanistan".
Personal life.
Hosseini is married to Roya and they have two children, Haris and Farah. The family reside in Northern California. He is fluent in Persian and Pashto, and has described himself as a secular Muslim.
Awards.
Exclusive Books Boeke Prize
British Book Awards
Book Sense Book of the Year Awards
California Book Award Silver Medal
Goodreads Choice Award
Other Awards.
In 2008, he received the Golden Plate Award of the American Academy of Achievement.


Nzolameso v City of Westminster

Nzolameso v City of Westminster was a 2015 judgment by the Supreme Court of the United Kingdom that considered the way that local councils fulfil their duty to house the homeless. Section 208(1) of the Housing Act 1996 requires all local housing authorities to secure accommodation within their own district "so far as reasonably practicable".
Facts.
In November 2012, Titina Nzolameso, a single mother of five children was evicted from her home in Westminster. She applied to Westminster City Council under the relevant homelessness provisions and in January 2013 the council offered her a house in Bletchley (approximately 50 miles away). Ms. Nzolameso turned this offer down on the basis that she was settled in Westminster, had ongoing health concerns and did not want her children to have to change schools. Given that the offer of housing had been refused, Westminster City Council then served notice that their housing duty had come to an end. Ms. Nzolameso then sought to review the decision under s.202 of the Housing Act 1996.
Judgment.
Supreme Court.
The decision by Westminster City Council that their housing duty had come to an end was quashed.
Handing down the leading judgment Lady Hale stated that because the authority had not explained and evidenced the reasons for their decision as required


Tineke Huizinga

Johanna Catharina "Tineke" Huizinga-Heringa (born 16 February 1960) is a Dutch politician of the Christian Union (CU) party.
Huizinga grew up in Amersfoort; both of her parents were teachers. After attending gymnasium, she began to study law at the University of Utrecht. She became involved in the Christian student's association Ichtus, where she met her future husband. They married in 1982. After passing her candidate exams (roughly equivalent of a bachelor's degree), she stopped her studies and moved to Heerenveen. She became a housewife and mother of three children.
She volunteered as translator at a Christian foundation, Open Doors, which advocates the interest of persecuted Christians worldwide. She became involved in the cases of asylum seekers and refugees and worked as a volunteer for VluchtenlingenWerk Nederland. Because of her involvement with social and religious issues, the Reformatory Political Federation asked her to become their top candidate in Heerenveen for the 1998 municipal elections. She was elected into the Heerenveen municipal council.
In 2002 she was elected member of House of Representatives. She was elected on basis of preference votes. The ChristianUnion only got four seats and she was seventh candidate, but because so many voters voted for her she entered parliament at the cost of prominent GPV leader Eimert van Middelkoop. She was member of the parliamentary research committee into the Srebrenica massacre. In the 2003 elections she was re-elected, again with preference votes, now at the cost of Leen van Dijke. She was fourth candidate and the ChristianUnion only got three seats. In parliament she had been occupied with foreign affairs, international development, migration, integration, spatial planning and the environment. She was secretary of the parliamentary party.
As Secretary of State for Transport, Public Works and Water Management, Huizinga survived a motion of no confidence in April 2008 over the (supposedly failed) introduction of a MIFARE-based nationwide public transport payment system.
External links.


Arthur Stedman Cotton

Brigadier-General Arthur Stedman Cotton, (18 August 1873 – 13 September 1952) was a British Army officer.
Early life and career.
Cotton was the son of Major J. W. M. Cotton of Regent's Park, London. He was educated at Merchant Taylors' School and the Royal Military Academy, Woolwich, from which he was commissioned second lieutenant in the Royal Artillery on 11 September 1893. He was promoted lieutenant on 14 September 1896, captain on 28 July 1900, and major on 24 September 1910. He served in the Boxer Rebellion in 1900.
First World War and Russian Civil War.
During the First World War, Cotton served on the Western Front with the 2nd Division, 5th Division, 32nd Division, and 41st Division.
He was wounded three times, mentioned in despatches nine times, and awarded the Distinguished Service Order (DSO) in 1915. He was promoted to the temporary rank of lieutenant-colonel on 13 October 1915 and was made a substantive lieutenant-colonel in 1916. He was appointed Brigadier-General, Royal Artillery (BGRA; i.e. the divisional artillery commander) of 41st Division on 12 October 1917 and served in this post until 14 April 1919. On 3 June 1919, he was promoted brevet colonel for his war service.
In 1919, he served as artillery adviser with the British Military Mission in South Russia. For gallantry during the Russian Civil War, he was awarded the Albert Medal on 14 July 1920. The citation reads:
Captain Thomas Stratford Knill, the master of the "War Pike", was also awarded the Albert Medal for the same incident.
Cotton was appointed Companion of the Order of St Michael and St George (CMG) in 1919 and awarded the French "Croix de guerre" with Palms and the Belgian "Croix de guerre". He was also appointed Officer of the Order of St Maurice and St Lazarus by Italy and was awarded the Order of St Vladimir 3rd Class by Russia. On 15 March 1920, he was appointed Commander of the Order of the British Empire (CBE) for his services in South Russia.
Post-war.
On 1 January 1921, Cotton was promoted to the substantive rank of colonel. He served as Colonel-Commandant, Royal Artillery (CCRA) of the 28th Division from 29 September 1922 to 1 October 1923 during the Chanak Crisis, and also temporarily commanded the division. Reverting to colonel once more, he served as Commander, Royal Artillery (CRA) with the Territorial Army's 56th (1st London) Division from 21 October 1924 to 8 January 1926.
He completed his service in India, as CCRA in Southern Command from 14 February 1926 to 30 April 1927, and then as CCRA (later Brigadier, Royal Artillery (BRA) from 1 June 1928) in Northern Command, headquartered at Poona, from 30 April 1927 until 15 April 1930. For this service, he was appointed Companion of the Order of the Bath (CB) in the 1930 Birthday Honours. He retired on 14 June 1930 with the honorary rank of brigadier-general.
After retirement, he lived in Bournemouth, where he served in civil defence during the Second World War. In 1903, he married Rose Bousfield. They had one daughter, Joan Bousfield Cotton.


List of law enforcement awards and honors

This list of law enforcement awards and honors is an index to articles that describe notable awards related to law enforcement. The list is organized by region and country. Most of the awards are to law enforcement officers in the country granting the award.


Burnt Timber Act

The Burnt Timber Act of 1913 authorized the United States Secretary of the Interior to sell at auction any dead or damaged timber on Federal lands.


Das v Linden Mews Ltd

 is an English land law case, concerning rights of way (a major type of easements).
Facts.
The company, Linden Mews Ltd, was formed by certain residents of Linden Mews in Notting Hill to buy the road, where in places the residents regularly historically parked on average one car per house which was all the space available. The exception was nos. 4 and 5 who owned a small garden as separate parcels of land (tenements) for parking beyond the end of the road since 1988 and in 1998 opened up part of the wall, affixing substantial gates to access it more easily. These two residents claimed an easement, and the company counterclaimed trespass seeking an injunction (and failing which an agreement to refrain from parking in the residents' yards at the end of the road in favour of their accepting its proposed levy of parking charges on the road it owned).
The company said/argued:
The two households argued:
In the court below the judge in the Central London County Court found strongly for the private road company, granting them a restrictive injunction against Das and the other neighbour.
Judgment.
Buxton LJ gave the substantive judgment with which the fellow two judges agreed. He held there was no easement for parking, but the judge had been wrong to award an injunction, and should have considered whether damages in lieu would have been more appropriate, and how much. The case was remitted back to the trial judge for a fresh exercise of his discretion as to whether an injunction should be granted following the guidelines set down by the Court of Appeal.
The panel of three judges agreed a dominant owner (the residents) could only as of right use a right of way granted (or relying its period of exercise for obtaining it "by prescription") for the enjoyment and for the purposes of the dominant tenement. They could not use it for the additional land they acquired. The only automatically permissible enlargement of the dominant tenement would be an expansion of business, otherwise an express grant of easement would need to be negotiated, such as at a market price. This rule was upheld in "Alvis v Harrison" (1991) in the House of Lords, a Scottish case stated by the House equally to apply English law.


Colin Harper (footballer)

Colin Harper (25 July 1946 – 29 March 2018) was an English professional footballer and football manager. He played as a left-back, and made 198 league and cup appearances in a 12-year career in the Football League.
He spent 1966 to 1977 at Ipswich Town, helping the club to win the Second Division title in 1967–68 and then to go on to compete in Europe under Bobby Robson. In 1976–77 he played on loan at Grimsby Town and Cambridge United, helping Ron Atkinson's Cambridge to the Fourth Division title. He became player-manager for brief spells at Port Vale, Waterford (Ireland), Sudbury Town and Chelmsford City, before entering the building trade. He was inducted into the Ipswich Town F.C. Hall of Fame in 2016.
Playing career.
Ipswich Town.
Harper started his career at Ipswich Town, who were struggling in the Second Division in 1965–66. He made his first-team debut on 19 February, in a 3–0 defeat at Plymouth Argyle. He turned professional under manager Bill McGarry, and helped the "Blues" to rise to fifth in 1966–67, before finishing top of the division in 1967–68. They retained their First Division status in 1968–69, after Bobby Robson was appointed as manager. Ipswich hovered above the relegation places in 1969–70 and 1970–71, before rising to 13th in 1971–72. He scored his first senior goal on 9 October 1971, in a 1–1 draw with Nottingham Forest at Portman Road. He was sent off for the first-time in his career on 15 April 1972, during a 0–0 draw with Sheffield United. Three days later he scored the second goal of his career, his header helping to deny Manchester City the title as it proved to be the winning goal in a 2–1 victory on the penultimate day of the season.
Town finished fourth in 1972–73 and 1973–74. However Harper picked up a knee injury in 1973 that would plague the rest of his career. Their fourth-place finishes entitled them to compete in the UEFA Cup. They posted a third-place finish in 1974–75, and were just two points behind champions Derby County. Harper was granted a testimonial match in 1975. Ipswich dropped to sixth in 1975–76, before rising again to third-place in 1976–77, five points behind champions Liverpool. Harper had two loan spells in 1976–77, playing three Third Division games for relegated Grimsby Town and 15 games under Ron Atkinson on loan at Fourth Division champions Cambridge United.
Port Vale.
Harper joined Third Division club Port Vale as player-coach in July 1977, with manager Roy Sproson appointing him to replace Roy Chapman. He made his debut in a 1–1 draw at Wrexham on 27 August, but was to only make a further three appearances for the "Valiants" in 1977–78. He was made acting manager on 18 October 1977, and insisted that there was to be no smiling during training as it was a serious matter. His reign at Vale Park only lasted a month as new manager Bobby Smith brought in his own staff, including assistant Dennis Butler, and Harper's contract was cancelled by the club in January 1978.
Later career.
After leaving Port Vale he was then appointed player-manager of Waterford. He led the "Blues" to the FAI Cup semi-finals and fifth in the League of Ireland. He signed with Sudbury Town in September 1978. He gave up playing three months later due to arthritis in his knee, though he stayed on at the club as manager. He then moved on to Chelmsford City, and led the club to an 18th-place finish in the Southern League in 1980–81.
Post-retirement.
Harper became a builder after leaving the game. In May 2002, it was reported by the "Ipswich Star" that he had £7,000 worth of tools stolen from his van in Ipswich. He continued to follow Ipswich Town until his death from illness on 29 March 2018; he left behind wife Carol, and three children. An inquest revealed that he died from an asbestos-related disease, having been exposed to asbestos whilst working as an apprentice joiner and carpenter before he took up his football career.
Statistics.
Playing statistics.
Source:
Honours.
Individual


Volunteer Pilots Association

The Volunteer Pilots Association (VPA) is an American Public Benefit Flying (PBF) group founded in 1990. The Volunteer Pilots Association provides free non-emergency air transportation to and from medical appointments for patients with a financial need. Headquartered in southwestern Pennsylvania, the VPA is an all-volunteer non-profit organization. All member pilots fly privately owned planes and donate their time and flight expenses.
The VPA also transports donor organs and other time-critical medically related items and provides emergency/disaster relief as part emergency preparedness.
The VPA is one of only 70 volunteer pilot organizations in the nation—and the only one based in southwestern Pennsylvania—that fly medical assistance missions. The organization serves residents of Pennsylvania, Ohio, New Jersey, New York, Virginia, West Virginia, Maryland and Delaware and usually flies patients to and from health care centers that are up to 300 miles from their homes. For missions outside that radius, the VPA partners with other volunteer pilot organizations. Flights are made in general aviation aircraft, usually seating four to six people, including the crew.
By using general aviation aircraft the VPA is able to operate in areas that don't have airline service. The VPA can operate in rural areas and, unlike airlines, can land and take off on relatively short runways. In the US there are over 13 thousand public and private airports that can be used by general aviation aircraft, of which only a few hundred can be used by the airlines.
The VPA is a member of the Air Care Alliance.
Method of operation.
VPA Member Pilots provide free air transportation for people in need who must travel long distances to seek medical attention not readily available in their area. VPA Pilots also assist with the transport of donor organs. Occasionally the person transported is not a patient, but a relative or close friend of a patient, for example when a terminally ill patient cannot leave the hospital anymore.
The VPA does not provide the actual transportation. Instead, the VPA links member pilots and patients (and their relatives) and hospital workers or social workers. A pilot can then accept a mission from the missions organized by one of the VPA Mission Coordinators.
The VPA also engages VPA Volunteers, for example to assist patients who require specialized medical treatment at the facility or who need general help with the transportation.
A VPA mission is organized by a VPA Mission Coordinator. Usually a social worker or hospital workers contacts a VPA Mission Coordinator to request a flight. Then flight dates, times, locations, number of passengers, and other medical contact people are discussed. The VPA Mission Coordinator then sends out an email to all VPA Pilots and enters them in the web-based on-line database, where pilots can log in and browse all available missions at a glance, along with pertinent flight information and maps.
Not every patient can be transported by the VPA. All VPA Patients must be medically stable and capable of walking on their own and sitting upright in an unpressurised aircraft unassisted. The VPA also does not provide emergency flights or air ambulance flights.
VPA Pilots.
The VPA Pilots volunteer all costs associated with the flight: time, direct operating expenses, fees, and indirect expenses, such as wear and tear or depreciation. The VPA Pilots can use their own personal aircraft or use rented airplanes. Pilots must meet certain minimum flight experience requirements before they are permitted to fly for the VPA, and they have to follow the guidelines of the VPA Guidebook. The VPA Pilots generally have an instrument-rating, and some have a Commercial Pilot License.
The VPA Pilots provide a variety of aircraft, ranging from Piper Cherokees to a CitationJet.
Operating area.
The VPA generally operates in the NorthEast quadrant of the United States – serving residents of Pennsylvania, Ohio, New Jersey, New York, Virginia, West Virginia, Maryland and Delaware and usually flying patients to and from health care centers that are up to 300 miles from their homes. On occasion, for flights of greater distances, the VPA partners with other volunteer pilot groups in other parts of the country.
Awards and distinctions.
The VPA has received a variety of awards and distinctions that reflect its commitment to community service:


Outer Continental Shelf Lands Act


Sister Jeanne Cashman

Sister Jeanne Cashman is the founder and executive director of Sojourners’ Place, a shelter in Delaware for homeless men and women that helps them to get on their feet. Cashman founded Sojourners’ Place in 1991. She took her vows in 1972 and became an educator in New York and at Ursuline Academy in Wilmington, Delaware. Seeing the need for an open ended time frame for homeless people to develop skills, she opened Sojourners’ Place where residents stay, on average, for six to eight months. 70% of the people who stay with them after prison leave successfully. She is also part of the Delaware “God Squad” that fights for interfaith acceptance. Together with Rabbi Peter Grumbacher and the Lutheran Rev. David Mueller she team-teaches a class each February at the Osher Lifelong Learning Institute at the University of Delaware in Wilmington.


Hope Atlanta

HOPE Atlanta, the programs of Travelers Aid of Metropolitan Atlanta, is a non-profit organization that has served the metro-Atlanta area for 112 years. Since its inception in 1900, the organization has provided services to over one million people in need throughout the counties surrounding Atlanta, Georgia.
HOPE Atlanta is also notable for the role it has played in Atlanta's - and the United States' - history. What began as a one-man operation outside the Atlanta Railroad Depot aiding travelers seeking support and shelter, soon expanded into a widespread effort to help those in need. This expansion began with the adoption of the program by Women's Associations of various denominations in the first decade of the 1900s.
In 1917, various travelers aid programs throughout the United States were united as "Travelers Aid International" The Atlanta service organization is noted for leading this unification. This same year, with the United States' entry into World War I, programs (often referred to as "Troop Transit" efforts) to assist traveling servicemen and their families were put into place.
On March 11, 1919, with the hiring of Sarah Brinson and Maggie Richardson at the Terminal Railroad Station, the then "Travelers Aid of Metropolitan Atlanta" became the first non-profit group in Atlanta to integrate – hiring and serving individuals of all races.
In the years since, the programs of travelers aid have continued to expand and offer various services. For the past 25 years, Atlanta has been a popular destination for relocation east of the Mississippi River, necessitating these continuing services. It is expected that nearly 75,000 people in Georgia will be homeless at some point this year.
These services have expanded beyond the aid for travelers offered by "Travelers Aid International." While these remain as areas of service, HOPE Atlanta also provides assistance to the homeless, help for victims of domestic violence, assistance to HIV/AIDS patients, and crisis management for those in need. The current mission of HOPE Atlanta is four-tiered – to provide Housing, Outreach, Prevention, and Emergency Services. HOPE Atlanta continues to serve more than 15,000 individuals per year, approximately one-third of whom are children.


Peter Pain

Peter Richard Pain (6 September 1913 – 16 January 2003) was a British High Court judge, who for many years specialised in labour law.
Born in Marlborough in Wiltshire, Pain's father was a solicitor. He was educated at Westminster School and Christ Church, Oxford, then became a barrister at Lincoln's Inn. In the early 1930s, he visited a Hitler Youth camp, and the experience convinced him that war was inevitable, and that he should oppose it by becoming a socialist. He joined the Labour Party, for which he stood unsuccessfully in the 1937 Farnham by-election.
Pain was rejected for military service in World War II due to his health, so he joined the Auxiliary Fire Service. He worked with John Horner for the right of auxiliary fire crew to join the Fire Brigades Union.
After the war, Pain initially worked for Walter Raeburn, then built up a practice with Morris Finer and other colleagues, in later years become its head of chambers. He initially focusing on personal injury claims. and his expertise in the field was often called on by trade unions. In 1965, he was made a Queen's Counsel, and in 1972 he was made a Bencher at Lincoln's Inn. He became a leader in the developing field of labour law, taking many cases at the National Industrial Relations Court. When this closed, in 1975, he was appointed as a judge at the High Court of Justice.
Pain was strongly opposed to racism, and following Enoch Powell's Rivers of Blood speech, he volunteered as the chair of the Race Relations Board Conciliation Committee, serving from 1968 until 1971. He then became chair of the South Metropolitan Conciliation Committee. He also served on the Parole Board from 1978 to 1980.
In 1988, Pain was given his own court, with responsibility for adjudicating on pre-trial procedures such as injunctions. He retired in 1993, the last British judge to work regularly past the age of 80.


Tetracycline antibiotics

Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of "Streptomyces" bacteria or produced semi-synthetically from those isolated compounds. Tetracycline molecules comprise a linear fused tetracyclic nucleus (rings designated A, B, C and D) to which a variety of functional groups are attached. Tetracyclines are named for their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide.
While all tetracyclines have a common structure, they differ from each other by the presence of chloride, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.
Tetracyclines were discovered in the 1940s and exhibited activity against a wide range of microorganisms including gram-positive and gram-negative bacteria, chlamydiae, mycoplasmas, rickettsiae, and protozoan parasites. Tetracycline itself was discovered later than chlortetracycline and oxytetracycline but is still considered as the parent compound for nomenclature purposes.
Tetracyclines are among the cheapest classes of antibiotics available and have been used extensively in prophylaxis and in treatment of human and animal infections, as well as at subtherapeutic levels in animal feed as growth promoters.
Tetracyclines are growth inhibitors (bacteriostatic) rather than killers of the infectious agent (bacteriocidal) and are only effective against multiplying microorganisms. They are short-acting and passively diffuse through porin channels in the bacterial membrane. They inhibit protein synthesis by binding reversibly to the bacterial 30S ribosomal subunit and preventing the aminoacyl tRNA from binding to the A site of the ribosome. They also bind to some extent the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.
Tetracyclines all have the same antibacterial spectrum, although there are differences in species' sensitivity to types of tetracyclines. Tetracyclines inhibit protein synthesis in both bacterial and human cells. Bacteria have a system that allows tetracyclines to be transported into the cell, whereas human cells do not. Human cells therefore are spared the effects of tetracycline on protein synthesis.
Tetracyclines retain an important role in medicine, although their usefulness has been reduced with the onset of antibiotic resistance. Tetracyclines remain the treatment of choice for some specific indications.
Because not all of the tetracycline administered orally is absorbed from the gastrointestinal tract, the bacterial population of the intestine can become resistant to tetracyclines, resulting in overgrowth of resistant organisms. The widespread use of tetracyclines is thought to have contributed to an increase in the number of tetracycline-resistant organisms, in turn rendering certain infections more resilient to treatment.
Tetracycline resistance is often due to the acquisition of new genes, which code for energy-dependent efflux of tetracyclines or for a protein that protects bacterial ribosomes from the action of tetracyclines. Furthermore, a limited number of bacteria acquire resistance to tetracyclines by mutations.
Medical uses.
Tetracyclines are generally used in the treatment of infections of the urinary tract, respiratory tract, and the intestines and are also used in the treatment of chlamydia, especially in patients allergic to β-lactams and macrolides; however, their use for these indications is less popular than it once was due to widespread development of resistance in the causative organisms.
Tetracyclines are widely used in the treatment of moderately severe acne and rosacea (tetracycline, oxytetracycline, doxycycline or minocycline).
Anaerobic bacteria are not as susceptible to tetracyclines as are aerobic bacteria.
Doxycycline is also used as a prophylactic treatment for infection by "Bacillus anthracis" (anthrax) and is effective against "Yersinia pestis", the infectious agent of bubonic plague. It is also used for malaria treatment and prophylaxis, as well as treating elephantitis filariasis.
Tetracyclines remain the treatment of choice for infections caused by chlamydia (trachoma, psittacosis, salpingitis, urethritis and "L. venereum" infection), Rickettsia (typhus, Rocky Mountain spotted fever), brucellosis and spirochetal infections (borreliosis, syphilis and Lyme disease). They are also used in veterinary medicine.
They may have a role in reducing the duration and severity of cholera, although drug-resistance is mounting and their effect on overall mortality is questioned.
Side effects.
Side-effects from tetracyclines are not common, but of particular note is phototoxicity. It increases the risk of sunburn under exposure to light from the sun or other sources. This may be of particular importance for those intending to take on vacations long-term doxycycline as a malaria prophylaxis.
They may cause stomach or bowel upsets, and, on rare occasions, allergic reactions. Very rarely, severe headache and vision problems may be signs of dangerous secondary intracranial hypertension, also known as idiopathic intracranial hypertension.
Tetracyclines are teratogens due to the likelihood of causing teeth discolouration in the fetus as they develop in infancy. For this same reason, tetracyclines are contraindicated for use in children under 8 years of age. Some adults also experience teeth discoloration (mild grey hue) after use. They are, however, safe to use in the first 18 weeks of pregnancy.
Some patients taking tetracyclines require medical supervision because they can cause steatosis and liver toxicity.
Cautions.
Tetracyclines should be used with caution by those with liver impairment. Also, because the molecules are soluble in water it can worsen kidney failure (this is not true of the lipid-soluble agents doxycycline and minocycline). They may increase muscle weakness in myasthenia gravis and exacerbate systemic lupus erythematosus. Antacids containing aluminium and calcium reduce the absorption of all tetracyclines, and dairy products reduce absorption greatly for all but minocycline.
The breakdown products of tetracyclines are toxic and can cause Fanconi syndrome, a potentially fatal disease affecting proximal tubular function in the nephrons of the kidney. Prescriptions of these drugs should be discarded once expired because they can cause hepatotoxicity.
It was once believed that tetracycline antibiotics impair the effectiveness of many types of hormonal contraception. Recent research has shown no significant loss of effectiveness in oral contraceptives while using most tetracyclines. Despite these studies, many physicians still recommend the use of barrier contraception for people taking any tetracyclines to prevent unwanted pregnancy.
Contraindications.
Tetracycline use should be avoided in pregnant or lactating women, and in children with developing teeth because they may result in permanent staining (dark yellow-gray teeth with a darker horizontal band that goes across the top and bottom rows of teeth), and possibly affect the growth of teeth and bones.
Usage during the first 12 weeks of pregnancy does not appear to increase the risk of any major birth defects. There may be a small increased risk for minor birth defects such as an inguinal hernia, but the number of reports is too small to be sure if there actually is any risk.
In tetracycline preparation, stability must be considered in order to avoid formation of toxic epi-anhydrotetracyclines.
Mechanism of action.
Tetracycline antibiotics are protein synthesis inhibitors. They inhibit the initiation of translation in variety of ways by binding to the 30S ribosomal subunit, which is made up of 16S rRNA and 21 proteins. They inhibit the binding of aminoacyl-tRNA to the mRNA translation complex. Some studies have shown that tetracyclines may bind to both 16S and 23S rRNAs. Tetracyclines also have been found to inhibit matrix metalloproteinases. This mechanism does not add to their antibiotic effects, but has led to extensive research on chemically modified tetracyclines or CMTs (like incyclinide) for the treatment of rosacea, acne, diabetes and various types of neoplasms.
It has been shown that tetracyclines are not only active against broad spectrum of bacteria, but also against viruses, protozoa that lack mitochondria and some noninfectious conditions. The binding of tetracyclines to cellular dsRNA (double stranded RNA) may be an explanation for their wide range of effect. It can also be attributed to the nature of ribosomal protein synthesis pathways among bacteria.
Incyclinide was announced to be ineffective for rosacea in September 2007.
Several trials have examined modified and unmodified tetracyclines for the treatment of human cancers; of those, very promising results were achieved with CMT-3 for patients with Kaposi Sarcoma.
Structure-activity relationship.
Tetracyclines are composed of a rigid skeleton of 4 fused rings (see figure 1). The rings structure of tetracyclines is divided into an upper modifiable region and a lower non modifiable region (see figure 2). An active tetracycline requires a C10 phenol as well as a C11-C12 keto-enol substructure in conjugation with a 12a-OH group and a C1-C3 diketo substructure. Removal of the dimethylamine group at C4 reduces antibacterial activity. Replacement of the carboxylamine group at C2 results in reduced antibacterial activity but it is possible to add substituents to the amide nitrogen to get more soluble analogs like the prodrug lymecycline. The simplest tetracycline with measurable antibacterial activity is 6-deoxy-6-demethyltetracycline and its structure is often considered to be the minimum pharmacophore for the tetracycle class of antibiotics. C5-C9 can be modified to make derivatives with varying antibacterial activity.
Mechanism of resistance.
Cells can become resistant to tetracycline by enzymatic inactivation of tetracycline, efflux, ribosomal protection, reduced permeability and ribosome mutation.
Inactivation is the rarest type of resistance, where NADPH-dependent oxidoreductase, a class of antibiotic destructase, modifies the tetracycline antibiotic at their oxidative soft spot leading to an inactivation of the tetracycline antibiotic. For example, the oxireductase makes a modification on the C11a site of oxytetracycline. Both Mg2+ chelation and ribosome binding are required for the biological activity of oxytetracycline and the modification attenuate the binding, leading to inactivation of the oxytetracycline antibiotic.
In the most common mechanism of reaction, efflux, various resistance genes encode a membrane protein that actively pumps tetracycline out of the cell by exchanging a proton for a tetracycline cation complex. This exchange leads to a reduced cytoplasmic concentration of tetracycline.
In ribosomal protection, a resistance gene encodes a protein that can have several effects, depending on what gene is transferred. Twelve classes of ribosomal protection genes/proteins have been found.
Possible mechanisms of action of these protective proteins include:
Administration.
When ingested, it is usually recommended that the more water-soluble, short-acting tetracyclines (plain tetracycline, chlortetracycline, oxytetracycline, demeclocycline and methacycline) be taken with a full glass of water, either two hours after eating or two hours before eating. This is partly because most tetracyclines bind with food and also easily with magnesium, aluminium, iron and calcium, which reduces their ability to be completely absorbed by the body. Dairy products, antacids and preparations containing iron should be avoided near the time of taking the drug. Partial exceptions to these rules occur for doxycycline and minocycline, which may be taken with food (though not iron, antacids, or calcium supplements). Minocycline can be taken with dairy products because it does not chelate calcium as readily, although dairy products do decrease absorption of minocycline slightly.
History.
The history of the tetracyclines involves the collective contributions of thousands of dedicated researchers, scientists, clinicians, and business executives. Tetracyclines were discovered in the 1940s, first reported in scientific literature in 1948, and exhibited activity against a wide range of microorganisms. The first members of the tetracycline group to be described were chlortetracycline and oxytetracycline. Chlortetracycline (Aureomycin) was first discovered as an ordinary item in 1945 and initially endorsed in 1948 by Benjamin Minge Duggar, a 73-year-old emeritus professor of botany employed by American Cyanamid – Lederle Laboratories, under the leadership of Yellapragada Subbarow. Duggar derived the substance from a Missouri soil sample, golden-colored, fungus-like, soil-dwelling bacterium named Streptomyces aureofaciens.
About the same time as Lederle discovered aureomycin, Pfizer was scouring the globe for new antibiotics. Soil samples were collected from jungles, deserts, mountaintops, and oceans. But ultimately Oxytetracycline (terramycin) was isolated in 1949 by Alexander Finlay from a soil sample collected on the grounds of a factory in Terre Haute, Indiana. It came from a similar soil bacterium named Streptomyces rimosus. From the beginning, terramycin was a molecule enveloped in controversy. It was the subject of the first mass-marketing campaign by a modern pharmaceutical company. Pfizer advertised the drug heavily in medical journals, eventually spending twice as much on marketing as it did to discover and develop terramycin. Still, it turned Pfizer, then a small company, into a pharmaceutical giant.
The Pfizer group, led by Francis A. Hochstein, in loose collaboration with and Robert Burns Woodward, determined the structure of oxytetracycline, enabling Lloyd H. Conover to successfully produce tetracycline itself as a synthetic product. In 1955, Conover discovered that hydrogenolysis of aureomycin gives a deschloro product that is just as active as the original product. This proved for the first time that chemically modified antibiotics could have biological activity. Within a few years, a number of semisynthetic tetracyclines had entered the market, and now most antibiotic discoveries are of novel active derivatives of older compounds.
Other tetracyclines were identified later, either as naturally occurring molecules, e.g., tetracycline from S. aureofaciens, S. rimosus, and S. viridofaciens and dimethyl-chlortetracycline from S. aureofaciens, or as products of semisynthetic approaches, e.g., methacycline, doxycycline, and minocycline.
Research conducted by anthropologist George J. Armelagos and his team at Emory University showed that ancient Nubians from the post-Meroitic period (around AD 350) had deposits of tetracycline in their bones, detectable through analyses of cross-sections through ultraviolet light – the deposits are fluorescent, just as are modern ones. Armelagos suggested that this was due to ingestion of the local ancient beer (very much like the Egyptian beer), made from contaminated stored grains.
Development.
Tetracyclines were noted for their broad spectrum antibacterial activity and were commercialized with clinical success beginning in the late 1940s to the early 1950s. The second-generation semisynthetic analogs and more recent third-generation compounds show the continued evolution of the tetracycline platform towards derivatives with increased potency as well as efficacy against tetracycline-resistant bacteria, with improved pharmacokinetic and chemical properties.
Shortly after the introduction of tetracycline therapy, the first tetracycline-resistant bacterial pathogen was identified. Since then, tetracycline-resistant bacterial pathogens have continued to be identified, limiting tetracycline's effectiveness in treatment of bacterial disease.
Glycylcyclines and fluorocyclines are new classes of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection.
In 2005, tigecycline, the first member of a new subgroup of tetracyclines named glycylcyclines, was introduced to treat infections that are resistant to other antimicrobials. Although it is structurally related to minocycline, alterations to the molecule resulted in its expanded spectrum of activity and decreased susceptibility to the development of resistance when compared with other tetracycline antibiotics. Like minocycline, tigecycline binds to the bacterial 30S ribosome, blocking the entry of transfer RNA. This ultimately prevents protein synthesis and thus inhibiting bacterial growth. However, the addition of an N,N,-dimethylglycylamido group at the 9 position of the minocycline molecule increases the affinity of tigecycline for the ribosomal target up to 5 times when compared with minocycline or tetracycline. This allows for an expanded spectrum of activity and decreased susceptibility to the development of resistance. While tigecycline was the first tetracycline approved in over 20 years, other, newer versions of tetracyclines are currently in human clinical trials.
Use as research reagents.
Members of the tetracycline class of antibiotics are often used as research reagents in "in vitro" and "in vivo" biomedical research experiments involving bacteria as well in experiments in eukaryotic cells and organisms with inducible protein expression systems using tetracycline-controlled transcriptional activation. The mechanism of action for the antibacterial effect of tetracyclines relies on disrupting protein translation in bacteria, thereby damaging the ability of microbes to grow and repair; however protein translation is also disrupted in eukaryotic mitochondria leading to effects that may confound experimental results.
It can be used as an artificial biomarker in wildlife to check if wild animals are consuming a bait that contains a vaccine or medication. Since it is fluorescent and binds to calcium, a UV lamp can be used to check if it is in a tooth pulled from an animal. For example, it was used to check uptake of oral rabies vaccine baits by raccoons in the USA. However, this is an invasive procedure for the animal and labour-intensive for the researcher. Therefore, other dyes such as rhodamine B that can be detected in hair and whiskers are preferred.


Land and Environment Court of New South Wales

The Land and Environment Court of New South Wales is a court within the Australian court hierarchy established pursuant to the to hear environmental, development, building and planning disputes. The Court’s jurisdiction, confined to the state of New South Wales, Australia, includes merits review, judicial review, civil enforcement, criminal prosecution, criminal appeals and civil claims about planning, environmental, land, mining and other legislation.
History.
The Court was established on 1 April 1980 as the world's first environmental court that was also a superior court of record.
A Parliamentary review in 2001 noted "It is evident that there is some dissatisfaction within sections of the community about the role and operations of the Court".
Structure and jurisdiction.
The Court is a superior court of record. It consists of a Chief Judge, severals Judges, and Commissioners. The New South Wales Court of Criminal Appeal and the New South Wales Court of Appeal, both divisions of the Supreme Court of New South Wales, may hear appeals from the Court, depending on the nature of case. Appellants on constitutional issues may seek special leave for the matter to be heard before the High Court of Australia in certain circumstances.
The Court has appellate jurisdiction over the Local Court of New South Wales with respect to an environmental offence under the .
Current composition.
Judges have the same rank, title, status and precedence as the Judges of the Supreme Court of New South Wales. Judges preside over all Aboriginal land claims matters, most land tenure and compensation matters, and can hear matters in all other Classes of the Court’s jurisdiction.
The Judges, in order of seniority, are as follows:


European Refugee Fund

The European Refugee Fund (ERF) was a scheme designed to facilitate the sharing of the financial costs of the reception, integration and voluntary repatriation of refugees amongst European Union member states. All EU member states apart from Denmark participated in the ERF. The Fund financed both national and transnational projects, including providing skills and language training to refugees, improvements to reception facilities and refugee resettlement or relocation operations. The ERF was allocated €630 million in funding over the period 2008–13. It was set up in 2000, replacing previous ad hoc funding measures. In April 2014, the ERF, along with the European Integration Fund and the European Return Fund, was replaced by the Asylum Migration and Integration Fund (AMIF) established for the period 2014–20.


Safe as Houses

Safe as Houses is a Scottish television property programme on STV, hosted by sports broadcaster Ali Douglas and money advisor Fergus Muirhead.
The programme aimed to help viewers, whether they are a first time buyer or looking to expand their property empire.
"Safe as Houses" began airing on Thursday 19 July 2007, with the series ending on 6 September 2007.


James Mason

James Neville Mason (; 15 May 190927 July 1984) was an English actor. He achieved considerable success in British cinema before becoming a star in Hollywood. He was the top box-office attraction in the UK in 1944 and 1945; his British films included "The Seventh Veil" (1945) and "The Wicked Lady" (1945). He starred in "Odd Man Out" (1947), the first recipient of the BAFTA Award for Best British Film.
He starred in a number of successful British and American films from the 1950s to the early 1980s, including "", "A Star Is Born", "20,000 Leagues Under the Sea", "Lolita", "North by Northwest", "Journey to the Center of the Earth", "Bigger Than Life", "Julius Caesar", "Georgy Girl", "Heaven Can Wait", "The Boys from Brazil" and "The Verdict".
Mason was nominated for three Academy Awards, three Golden Globes (winning the Golden Globe in 1955 for "A Star is Born") and two BAFTA Awards throughout his career. Following his death in 1984, his ashes were interred near the tomb of his close friend, fellow English actor Sir Charlie Chaplin.
Early life, family, and education.
Mason was born on 15 May 1909, in Huddersfield, in the West Riding of Yorkshire, the youngest of three sons of John Mason and Mabel Hattersley, daughter of J. Shaw Gaunt. A wealthy wool merchant like his own father before him, John Mason travelled a good deal on business, mainly in France and Belgium; Mabel - who was "uncommonly well-educated" and had lived in London to study and begin work as an artist before returning to Yorkshire to care for her father - was "attentive and loving" in raising her sons. The Masons lived in a house in its own grounds on Croft House Lane in Marsh, which was replaced in the mid 1970s by flats called Arncliffe Court. A small residential development opposite where the house once stood is now called James Mason Court.
Mason was educated at Marlborough College, and earned a first in Architecture at Peterhouse, Cambridge, where he became involved in stock theatre companies in his spare time. He had no formal training in acting and initially embarked upon it for fun.
Career.
Early stage appearances.
After Cambridge, Mason made his stage debut in Aldershot in "The Rascal" in 1931.
He joined the Old Vic theatre in London under the guidance of Tyrone Guthrie. While there he appeared in productions of "The Cherry Orchard", "Henry VIII", "Measure for Measure", "The Importance of Being Earnest", "Love for Love", "The Tempest", "Twelfth Night", and "Macbeth". Featuring in many of these were Charles Laughton and Elsa Lanchester. In the mid-1930s he also appeared at the Gate Theatre, Dublin, notably in "Pride and Prejudice" with Betty Chancellor.
In 1933 Alexander Korda gave Mason a small role in "The Private Life of Don Juan" but sacked him three days into shooting.
Early films.
From 1935 to 1938, he starred in many British quota quickies, starting with his first film "Late Extra" (1935), in which he played the lead. Albert Parker directed. Mason appeared in "Twice Branded" (1936); "Troubled Waters" (1936), also directed by Parker; "Prison Breaker" (1936); "Blind Man's Bluff" (1936), for Parker's "The Secret of Stamboul" (1936), and "The Mill on the Floss" (1936), an "A" movie.
Mason had a key support role in Korda's "Fire Over England" (1937) with Laurence Olivier and Vivien Leigh. He was in another "A", "The High Command" (1937) directed by Thorold Dickinson, then went back to quickies, starring in "Catch As Catch Can" (1937), directed by Roy Kellino. Korda cast him as the villain in "The Return of the Scarlet Pimpernel" (1937)
Television.
Mason began appearing in some televised productions of plays, made in the very early days of television: "Cyrano de Bergerac" (1938), "The Moon in the Yellow River" (1938), "Bees on the Boat-Deck" (1939), "Square Pegs" (1939), "L’Avare" (1939), and "The Circle" (1939).
He returned to features with "I Met a Murderer" (1939) based on a story by Mason and Pamela Kellino, who also starred with Mason and whom he would marry. Her then-husband Roy Kellino directed.
Second World War.
He registered as a conscientious objector during World War II (causing his family to break with him for many years), but his tribunal exempted him only on the requirement to do non-combatant military service, which he refused; his appeal against this became irrelevant once he was included in a general exemption for film work.
In 1941–42 he returned to the stage to appear in "Jupiter Laughs" by A. J. Cronin.
He established himself as a leading man in Britain in a series of films: "The Patient Vanishes" (1941); "Hatter's Castle" (1941) with Robert Newton and Deborah Kerr; "The Night Has Eyes" (1941); "Alibi" (1942) with Margaret Lockwood; "Secret Mission" (1942); "Thunder Rock" (1942) with Michael Redgrave; and "The Bells Go Down" (1943) with Tommy Trinder.
Gainsborough melodramas and stardom.
Mason became hugely popular for his brooding anti-heroes in the Gainsborough series of melodramas of the 1940s, starting with "The Man in Grey" (1943). The film was a huge hit and launched him and co-stars Lockwood, Stewart Granger and Phyllis Calvert, to top level stars.
Mason starred in two war time dramas, "They Met in the Dark" (1943) and "Candlelight in Algeria" (1944), then returned to Gainsborough melodrama with "Fanny By Gaslight" (1944) with Granger and Calvert; it was another big hit.
Mason starred in "Hotel Reserve" (1944), a thriller, then did a ghost story for Gainsborough with Lockwood, "A Place of One's Own" (1945). Far more popular was a melodrama, "They Were Sisters" (1945).
Sydney Box cast Mason in the lead of a musical melodrama, "The Seventh Veil" (1945) alongside Ann Todd. It was a huge success in Britain and the US and demand for Mason was at a fever pitch. Exhibitors voted him the most popular star in Britain in each year between 1944 and 1947. They also thought he was the most popular international star in 1946; he dropped to second place the following year. He was the most popular male star in Canada in 1948.
Mason had a relatively minor role in "The Wicked Lady" (1945) with Lockwood, a big hit. Mason then received his best reviews to date playing a mortally wounded IRA bank robber on the run in Carol Reed's "Odd Man Out" (1947).
Mason was able to turn producer on a film with Box, written by his wife and starring Mason, "The Upturned Glass" (1947). It was not particularly successful. Neither was "Bathsheba", a play he and his wife did on Broadway.
Hollywood.
Mason went to Hollywood where his first film was "Caught" (1949), directed by Max Ophüls. He played Gustave Flaubert in MGM's "Madame Bovary" (1949).
Mason did another with Ophüls, "The Reckless Moment" (1949), then did "East Side, West Side" (1949) with Barbara Stanwyck at MGM and "One Way Street" (1950) at Universal. He made "Pandora and the Flying Dutchman" (1951) with Ava Gardner. None of these films was particularly successful.
"The Desert Fox" and 20th Century Fox.
Mason's Hollywood career was revived when cast as General Rommel in "" (1951), directed by Henry Hathaway. To do the film he agreed to sign a contract with 20th Century Fox for seven years at one film a year.
Mason did a film at Republic Pictures written by his wife and directed by Roy Kellino, "Lady Possessed" (1951). At Fox he played a spy in "5 Fingers" (1951) directed by Joseph L. Mankiewicz.
MGM hired him to play Rupert of Hentzau in "The Prisoner of Zenda" (1952) opposite Granger. He was in the lower budgeted "Face to Face" (1952) then went to Paramount to play a villainous sea captain opposite Alan Ladd in "Botany Bay" (1953).
Mason was one of many stars in MGM's "The Story of Three Loves" (1953). At Fox he reprised his role as Rommel in "The Desert Rats" (1953), then he was reunited with Mankiewicz at MGM, playing Brutus in "Julius Caesar" (1953), opposite Marlon Brando. The film was very successful.
Mason worked with Carol Reed in "The Man Between" (1953), then Fox used him as a villain again in "Prince Valiant" (1954). Mason did another film with a screenplay by his wife and directed by Roy Kellino, "Charade" (1954).
Warner Bros., hired him to play Judy Garland's leading man in "A Star Is Born" (1954). He went over to Disney to play Captain Nemo in "20,000 Leagues Under the Sea" (1954), a huge hit. During 1954 and 1955, Mason was the host of some episodes of "Lux Video Theatre" on CBS television.
Mason appeared with Lucille Ball and Desi Arnaz in "Forever, Darling" (1956) then starred in and produced a film at Fox, "Bigger Than Life" (1956), directed by Nicholas Ray. Mason played a small-town school teacher driven insane by the effects of cortisone. He did another for Fox, the hugely popular melodrama, "Island in the Sun" (1957).
Later 1950s and early 1960s.
Mason began appearing regularly on television in shows such as "Panic!", "General Electric Theater", "Schlitz Playhouse", "Goodyear Theatre" and "Playhouse 90" (several episodes including "John Brown's Raid").
He starred in two thrillers for Andrew L. Stone, "Cry Terror!" (1958) and "The Decks Ran Red" (1958) then played a suave master spy in "North by Northwest" (1959) directed by Alfred Hitchcock.
At Fox he had a huge hit playing a determined scientist and explorer in "Journey to the Centre of the Earth" (1959), taking over a role meant for Clifton Webb. He did a comedy "A Touch of Larceny" (1960) and was Sir Edward Carson in "The Trials of Oscar Wilde" (1960).
He continued to appear on TV shows like "The DuPont Show with June Allyson", "Golden Showcase", "Theatre '62" and "The Alfred Hitchcock Hour".
He did "The Marriage-Go-Round" (1961), then played Humbert Humbert in Stanley Kubrick's version of "Lolita" (1962).
He starred in "Tiara Tahiti" (1962), then "Hero's Island" (1962), which he also produced. He was in "Torpedo Bay" (1963).
From 1963 to the end of the decade.
In 1963 Mason settled in Switzerland, and embarked on a transatlantic career. He began to drift into support roles, or second leads: the epic "The Fall of the Roman Empire" (1964); "The Pumpkin Eater" (1964), with Anne Bancroft; a river pirate who betrays Peter O'Toole's character in "Lord Jim" (1965); a Chinese noble in "Genghis Khan" (1965); "The Uninhibited" (1965); a guest role on "Dr Kildare"; James Leamington in the Swinging London-set "Georgy Girl" (1966), a role that earned him a second Academy Award nomination, for Best Actor in a Supporting Role.
He was in several episodes of "ITV Play of the Week" and he had the lead in "The Deadly Affair" (1967) for Sidney Lumet and "Stranger in the House" (1968).
He provided a supporting role in "Duffy" (1968) and "Mayerling" (1968) but was top billed in "The Sea Gull" (1968) for Sidney Lumet and starred as Bradley Morahan in "Age of Consent" (1969) for Michael Powell, a film which Mason also produced. He also had the star role in "Spring and Port Wine" (1970).
1970s.
Mason supported Charles Bronson in "Cold Sweat" (1970) and Lee Van Cleef in "Bad Man's River" (1971). He was a support in "Kill! Kill! Kill! Kill!" (1971) and top billed in "Child's Play" (1972) for Lumet, replacing Marlon Brando.
He was one of many stars in "The Last of Sheila" (1973) and played the evil Doctor Polidori in "" (1973). He had support roles in "The MacKintosh Man" (1973), "11 Harrowhouse" (1974), "The Marseille Contract" (1974), and "Great Expectations" (1974) and was top billed in "Mandingo" (1975).
Mason's later 70s performances included "Kidnap Syndicate" (1975), "The Left Hand of the Law" (1975), "Autobiography of a Princess" (1975), "Inside Out" (1975), "The Flower in His Mouth" (1975), "Voyage of the Damned" (1976), "Hot Stuff" (1977), "Cross of Iron" (1977), "Jesus of Nazareth" (1977), "The Yin and the Yang of Mr. Go" (1978), "The Water Babies" (1978), "Heaven Can Wait" (1978), "The Boys from Brazil" (1978), "Murder by Decree" (1979) (as Watson), "The Passage" (1979), "Bloodline" (1979) and as the vampire's servant, Richard Straker, in "Salem's Lot" (1979).
1980s.
Mason was in "North Sea Hijack" (1980), "Evil Under the Sun" (1982), "Ivanhoe" (1982), and "A Dangerous Summer" (1982).
One of his last roles, that of the corrupt lawyer Ed Concannon in "The Verdict" (1982), opposite Paul Newman, earned him his third and final Oscar nomination, for Best Actor in a Supporting Role.
He had parts in "Yellowbeard" (1983), "Alexandre" (1983), and "George Washington" (1984).
Narrator.
In 1967, Mason narrated the documentary "The London Nobody Knows". An ardent cinephile on top of his career interests, Mason narrated two British documentary series supervised by Kevin Brownlow: "Hollywood" (1980), on the silent cinema and "Unknown Chaplin" (1983), devoted to out-take material from the films of Sir Charlie Chaplin. Mason had been a long-time neighbour and friend of the comedian. In the late 1970s, Mason became a mentor to up-and-coming actor Sam Neill.
Final performances.
Having completed playing the lead role in "Dr. Fischer of Geneva" (1985), adapted from Graham Greene's eponymous novella for the BBC, he stepped into the role in "The Shooting Party" originally meant for Paul Scofield, who was unable to continue after being seriously injured in an accident on the first day of shooting. This was to be Mason's final screen performance in a feature film.
He did appear on TV in "A.D." (1985) and "The Assisi Underground" (1985).
Personal life.
Mason was a devoted lover of animals, particularly cats. He and his wife, Pamela Mason, co-authored the book "The Cats in Our Lives", which was published in 1949. James Mason wrote most of the book and also illustrated it. In "The Cats in Our Lives", he recounted humorous and sometimes touching tales of the cats (as well as a few dogs) he had known and loved.
In 1952, Mason purchased a house previously owned by Buster Keaton. He discovered reels of nitrate film thought to have been lost, stored in the house and produced by the comedian, such as "The Boat" (1921). Mason arranged to have the decomposing films transferred to safety stock and thus saved them from oblivion.
In his youth, Mason was a keen fan of his local Rugby League team, Huddersfield. In later years he also began to follow the fortunes of Huddersfield Town.
Mason was married twice:
Mason's autobiography, "Before I Forget", was published in 1981.
Death.
Mason survived a severe heart attack in 1959. He died as result of another heart attack on 27 July 1984 in Lausanne, Switzerland, and was cremated.
Mason left his entire estate to his second wife, Clarissa Kaye, but his will was challenged by his two children. The lawsuit had not been settled when she died on 21 July 1994 from cancer. Clarissa Kaye Mason left her holdings to the religious guru Sathya Sai Baba, including the actor's ashes which she had retained in their shared home. Mason's children sued Sai Baba and subsequently had Mason's ashes interred in Corsier-sur-Vevey, Vaud, Switzerland. The remains of Mason's friend Charlie Chaplin are in a tomb a few steps away. Mason's children specified that his headstone read: "Never say in grief you are sorry he's gone. Rather, say in thankfulness you are grateful he was here", words that were spoken to Portland Mason by U.S. Senator Ted Kennedy after the actor's death.


Taoyuan Aerotropolis

Taoyuan Aerotropolis () is a large urban planning development at the Taiwan Taoyuan International Airport in Taoyuan City, Taiwan.
The 4,500 hectare development, centered around the existing airport, will include a districts for transportation, logistics, industry, and residential development, and has been called "one of Taiwan’s largest national infrastructure projects ever." The Aerotropolis is expected to create 200,000-300,000 new jobs, generate annual revenues of NT$2.3 trillion (US$75.4 billion), and accommodate 4.5 million tons of container cargo a year.
The development may require the acquisition of up to 3,200 hectares of land and the relocation of over 40,000 people
A third runway and terminal will be added to Taiwan Taoyuan International Airport, boosting the capacity of the airport from 40 million to over 60 million passengers by 2025. Previously approved during the administration of Ma Ying-jeou, the Aerotropolis project proved to be controversial, "due to allegations of forced relocations, the prospect of added pollution, and insinuations of irregularities in land acquisition."
The Taoyuan City Mayor Cheng Wen-tsan, serving since 2014, has promised that the current, revamped version of the project will be developed according to five principles:
It will also strive to deliver low energy consumption, low pollution, and low water usage, along with high added value—guidelines that the mayor has dubbed "three lows and one high"—which will help resolve problems left from the Ma administration's approach to development.


Comedown (drugs)

Comedown or crashing is a phase of drug withdrawal that involves the deterioration in mood and energy that occurs when a psychoactive drug, typically a stimulant, clears from the blood. The improvement and deterioration of mood (euphoria and dysphoria) are represented in the cognitive schema as high and low elevations; thus, after the drug has "elevated" the mood (a state known as a high), there follows a period of "coming back down," which often has a distinct character from withdrawal in stimulants. Generally, a comedown ("down", "low", sometimes "crash") can happen to anyone as a transient symptom, but in people who are dependent on the drug (especially those addicted to it), it is an early symptom of withdrawal and thus can be followed by others.
Various drug classes, most especially stimulants and to a lesser degree opioids and sedatives, are subject to comedowns. A milder analogous mood cycle can happen even with blood sugar levels (thus sugar highs and sugar lows), which is especially relevant to people with diabetes mellitus and to parents and teachers managing children's behavior, as well as in adults with ADHD. Stimulant comedowns are unique in that they often appear very abruptly after a period of focus or high, and are typically the more intensely dysphoric phase of withdrawal than that following complete elimination from the bloodstream. Besides general dysphoria, this phase can be marked by frustration, anger, anhedonia, social withdrawal, and other symptoms characteristic to a milder mixed episode in bipolar disorder. Alertness and other general stimulant effects are still present.
For example, in an MDMA (ecstasy) comedown, if the user experiences severe, persisting emotional distress, such as panic attacks,
severe generalized anxiety, or insomnia following an MDMA session, a physician may prescribe a benzodiazepine (specifically,
lorazepam) and/or sleep aid (e.g., zolpidem), to alleviate those effects.


Ruth Lingford

Ruth Lingford is an Independent animator. Since 2005, she has taught at the Harvard University. She now holds a position as Faculty member in the Visual and Environmental Studies, where she is Senior lecturer and Director of Undergraduate Studies. She previously taught at the Royal College of Art and the National Film and Television School, UK. Before investing herself in Animation, she was an Occupational therapist working with the elders and people suffering from mental disorders. Lingford completed a BA in Fine Arts and Art History at the Middlesex Polytechnic (Middlesex University) from 1987 to 1990 and a MA at the Royal College of Art until 1992. In 2008, she received an Honorary Doctor of Arts degree from the University of Wolverhampton.
Animation work.
Early work.
Lingford began her work in animation when she made "Baggage" and "Crumble" (both 1992) as part of her MA. "Baggage" and "Crumble" circulated in some film festivals, after their debut at the Royal College of Art's graduation show, including the Animefest Zagred, and the Clermont-Ferrand International Short Film Festival. After their limited festival run, and struggles to find stability, Lingford made "What She Wants" (1994) with funding of a grant from the Animate! programme (co-founded by for the Arts Council of England/Channel 4). For "What She Wants", Lingford resorted to use her Amiga 1500 computer – having no access to animation equipments –, doing individual frames on Deluxe Paint. Lingford had learnt rudimentary usage of the computer in a workshop at the RCA, when hand-drawn animation remained the dominant technique. "What She Wants"'s individual images were saved across approximately 20 Floppy disks.
"Death and the Mother" and other acclaimed works.
On her next project, Ruth Lingford was invited at the Museum of the Moving Image, for an 'unusual' residency. Developing a second commission for Channel 4, "Death and the Mother" (1997), Lingford returned again to her rudimentary methods of computer animation. The creative process, however, would take place in full view of the people navigating through the museum : Lingford would be working in a glass room. The film drew inspiration from German expressionist woodcut, and catapulted Lingford on the international animation scene. Upon completion, in 1997, "Death and the Mother" won many awards, including one at Annecy International Animated Film Festival of the same year. The surface, content and reputation of "Death and the Mother" drew attention to Lingford from Orly Yadin and Sylvie Bringas. She was asked to collaborate on their project, "Silence" (1998), where Lingford would be working along Tim Webb on the animation of "Silence"'s sequence. Lingford worked on the first half of the film, which takes place in an animated Theresienstadt, while Webb worked on the second half, which takes place in Sweden. On "Silence", she returned to Deluxe Paint to draw preliminary images which were finished by Yadin. Overall, the visuals she helped build in "Silence" won several important awards including: the Gold Hugo for Animation Short at the 1998 Chicago International Film Festival and the Grand Prix of the 1999 Odense Film Festival.
Lingford's following project, "Pleasures of War", of the same year, moved against "the 'plastic' gloss-orientation of much computer-generated imagery". Perhaps due to the success of "Silence", she approached novelist and Christian theologian Sara Maitland, who Lingford remembered for her short story "The Swallow and the Nightingale" (from her "Far North and Other Dark Tales" collection)". Pleasures of War" was scripted by Maitland, who also collaborated on the general design of the work, based on the deuterocanonical Book of Judith – a story in which two women bargain sexual favors to protect their city from besiegers. Within the film is collaged newsreel from armed conflicts around the world and the victims of these conflicts.
From the 2000s onward.
"The Old Fools" (2002) was Ruth Lingford's following project, again, commissioned by Channel 4. It is an adaptation of the Philip Larkin's homonymous poem – written while her mother was in nursing home. In terms of style, "The Old Fools" marks a departure from Lingford's computer-drawn evocative imagery; its aesthetics, rather combining DV footage, are drawings and typography animated in After Effects and Painter. With the Shynola collective, Lingford worked next on a music video for the music band Unkle, "An Eye for an Eye" (2002). The collaboration was successful, and remained inlined with Lingford's previous imagery : "a sublimely creepy evocation of the biological drives and desires". Lingford also collaborated on a fellow Harvard professors' film: "Secrecy" (2008), where her animated sequences served "to create a contrast between imaginary and literal realms of the secrecy system". Likewise, she animated sequences from another film – "We Still Live Here: Âs Nutayuneân" (2010) – by Anne Makepeace.
"Little Deaths" (2010), Lingford's latest standalone work, begun after she received a 2008–09 Harvard Film Study Center Fellowship. In the pre-production process, she wanted to 'interview' people about their orgasms. Lingford recalled she expected her interviewees to lack proper words to describe their private experiences, but they did not. She used their commentary, in "celebrat[ing] key aspects of our experience that are often suppressed," and continued to develop her experimental aesthetic of animation "to evoke the elusive physical and emotional experience of orgasm".
As of recently, Lingford has been part of the band "What Time Is It, Mr. Fox?" for whom she has animated the song "The Ladies' Tree", and sang as a back vocalist.