The Hungarian occupation of Vidin was a period in the history of the city and region of Vidin (), today in northwestern Bulgaria, when it was called Banate of Bulgaria under the rule of King Louis I of Hungary from 1365 to 1369.

Brief war

Before 1359–1360, the former heir to the Bulgarian crown Ivan Sratsimir had established himself as the ruler of the Vidin appanage of the Second Bulgarian Empire and had turned it into a largely independent entity. In early 1365 Louis I of Hungary, who like his predecessors styled himself "king of Bulgaria" (rex Bulgariae) among other titles, demanded that Ivan Sratsimir acknowledge his suzerainty and become his vassal. After Sratsimir's refusal, the Hungarian king undertook a campaign to conquer the Tsardom of Vidin. On 1 May 1365, he set off from Hungary; he reached Vidin on 30 May and captured the city on 2 June, after a brief siege. Kommander of hungarian army palatine Nicholas Kont, the condottiere Ulrich I count of Zilli, Magister Stefan Sira, Magister Georgi Zekul and some other Hungarian knights distinguished themselves in the campaign for the capture of Tsardom of Vidin.
The Hungarians took Ivan Sratsimir and his family captive and imprisoned them in the Humnik fortress in Bosiljevo, Croatia. Shortly afterwards, the Hungarians seized the entire land of the Tsardom of Vidin (known as Bodony in Hungarian) and turned it into a province of the Kingdom of Hungary governed by a ban. Initially, the area was governed by Peter Himfi, the Count of Pozsony, and then by Denis Lackfi, styled "voivode of Transylvania, governor of Vidin and ruler of the counties of Temes and Szolnok".

Hungarian rule in Vidin
After establishing their administrative rule, the Hungarians proceeded to convert the local Bulgarian Orthodox population to Roman Catholicism with the assistance of Franciscan friars. Despite its short duration, this was one of the earliest Hungarian missionary dioceses. According to Hungarian data, the Franciscans converted 200,000 people or a third of the region's population; although the figure is considered grossly overestimated and unrealistic, among the converted were certainly Ivan Sratsimir and his royal family. That religious intolerance was reflected in the negative popular attitude towards the Hungarian overlordship, attested in a marginal note in an Orthodox religious book from the period: "This book was written by the sinful and unintelligent Dragan together with his brother Rayko in the days when the Hungarians ruled Vidin and it was great pain for the people at that time."

Ivan Sratsimir's father, Tsar Ivan Alexander, ruler of Bulgaria at Tarnovo, could do nothing to stop the Hungarian invasion and his son's capture. Several years later, however, he took advantage of Byzantine Emperor John V Palaiologos' detention at Vidin and Count of Savoy Amadeus VI's campaign on the Bulgarian Black Sea Coast to organize an Orthodox coalition and salvage Vidin. For joining the alliance, Ivan Alexander offered the Byzantine emperor the Black Sea ports south of Nesebar (Messembria); in return, however, John V had to pay 180,000 florins to Vladislav I Vlaicu, voivode of Wallachia. The Vlach voivode would, in return, seize Vidin and cede it to Ivan Alexander.

End of the banate
In 1369, the Hungarian occupation of Vidin was brought to an end. Although the initial campaign was not entirely successful because the Hungarians seized the city back, the ensuing negotiations between the Kingdom of Hungary and Ivan Alexander's allies, Vladislav I Vlaicu and Dobrotitsa, the despot of the semi-independent Dobrujan Principality of Karvuna, led to the return of the city to Bulgarian possession. It is thought that Ivan Sratsimir was reinstalled as the region's ruler in the autumn of 1369.

List of bans

References

Bibliography

  Engel, Pál (1996). Magyarország világi archontológiája, 1301–1457, I. ("Secular Archontology of Hungary, 1301–1457, Volume I"). História, MTA Történettudományi Intézete. Budapest. .
  Markó, László (2006). A magyar állam főméltóságai Szent Istvántól napjainkig: Életrajzi Lexikon ("Great Officers of State in Hungary from King Saint Stephen to Our Days: A Biographical Encyclopedia"). 2nd edition, Helikon Kiadó.

History of Vidin
Banates of the Kingdom of Hungary
1360s conflicts
1360s in Europe
14th century in Bulgaria
14th century in Hungary


Nemapogon cloacella, the cork moth,  is a species of tineoid moth. It belongs to the fungus moth family (Tineidae), and therein to the subfamily Nemapogoninae. Its junior synonym N. infimella was established by G.H. Heydenreich in the 1851 volume of his Lepidopterorum Europaeorum Catalogus Methodicus, but many sources still attribute it to G.A.W. Herrich-Schäffer, who supposedly narrowly beat Heidenreich in (re)describing the species. But as it seems, Herrich-Schäffer was merely one of the first to use the name proposed by Heydenreich, as the volume of his Systematische Bearbeitung der Schmetterlinge von Europa where he discussed the cork moth was not published until 1853 or 1854. That all nonwithstanding, the species had been already validly described by A.H. Haworth in the 1828 volume of Lepidoptera Britannica.

Description
This small moth has a wingspan of 10–18 mm. The forewings are irregularly mottled black, brown, white and grey, resembling close relatives such as the European corn moth (N. granella). The head has a tuft of pale yellow hairs.
The antennae are wire-shaped and about two-thirds as long as the front wings. The thorax is grey. The wing fringes on the forewing are alternately grey and white. The hind wings are dark grey-brown. The larva is white to pink with a reddish-brown head. The neck plate  is also reddish-brown.

Distribution and ecology
Nemapogon cloacella is a widespread species, found all across the western Palaeartic and North America, where it has recently been recorded from British Columbia. It is reportedly absent from France, but given that it occurs in all surrounding countries, this is unlikely to be correct. Its preferred habitat is woodland with a large amount of dead trees. The crepuscular adults are on the wing throughout the summer and are typically encountered at dusk but sometimes can be seen earlier in the day.

Biology
The caterpillars feed mainly on bracket fungi. Their food spectrum has been subject to considerable dispute in the past due to confusion with the European corn moth. Some claimed that N. cloacella caterpillars eat a wide range of food – dried fruit and mushrooms, seeds and other vegetable material, e.g. cereal grains, Capsicum annuum fruit, poppyseed (Papaver somniferum),  bitter almonds (Prunus amygdalus amara) or bilberries (Vaccinium), but even cork (hence its common name) and beeswax. Other authors stated that they were only found on the oak mazegill fungus (Daedalea quercina), and ascribed the wide range of foodstuffs to N. granella. But as it seems, neither extreme was correct; the caterpillars do eat preferentially fungi – not only the oak mazegill but also others (e.g. birch polypore, Piptoporus betulinus) –, feeding on plant debris and similar materials when their favorite food is not available.

Footnotes

References
  (2009): Nemapogon cloacella. Version 2.1, 2009-DEC-22. Retrieved 2010-MAY-06.
  (1942): Eigenartige Geschmacksrichtungen bei Kleinschmetterlingsraupen ["Strange tastes among micromoth caterpillars"]. Zeitschrift des Wiener Entomologen-Vereins 27: 105-109 [in German]. PDF fulltext
  [2010]: UKmoths – Nemapogon cloacella. Retrieved 2010-MAY-05.
  [2010]: Global Taxonomic Database of Tineidae (Lepidoptera) – Nemapogon cloacella. Retrieved 2010-MAY-06.
  (2003): Markku Savela's Lepidoptera and some other life forms – Nemapogon cloacellus [sic]. Version of 2003-DEC-27. Retrieved 2010-MAY-06.

External links
 lepiforum.de
 Info at wein-plus.eu

Nemapogoninae
Moths of Europe
Moths of Asia
Moths of North America


The 2008–09 UAE President's Cup was the 33rd season of the UAE President's Cup, the premier knockout tournament for association football clubs in the United Arab Emirates.

Al-Ahli went into this edition as the holders. Sharjah FC hold the most wins with 8 titles.

The cup winner were guaranteed a place in the 2010 AFC Champions League.

Round 1
24 teams play a knockout tie. 12 clubs advance to the next round. Ties played over 30 & 31 October 2008

Round 2

16 teams play a knockout tie. 8 clubs advance to the next round. Ties played over 28 & 29 November 2008

Quarter finals

8 teams play a knockout tie. 4 clubs advance to the next round. Ties played over 1 & 2 February 2009

Semi finals

4 teams play a knockout tie. 2 clubs advance to the Final Ties played on 24 February 2009

Final

13 April 2009

UAE President's Cup seasons
Uae Presidents Cup, 2008-09
President's Cup


Juan Diego is a Spanish compound name which may refer to many people, Including:

Juan Diego (actor) (1942–2022), a Spanish actor
Juan Diego Angeloni (born 1978), an Argentine rifle shooter
Juan Diego Bernardino (1460–1544), one of two Aztec peasants alleged to have had visions of the Virgin Mary as Our Lady of Galupe
Juan Diego Botto (born 1975), Argentine-Spanish actor
Juan Diego Covarrubias (born 1987), a Mexican actor
Juan Diego del Castillo (1744–1793), Spanish pharmacist and botanist
Juan Diego Flórez (born 1973), a Peruvian opera singer
Juan Diego González Alzate (born 1980), Colombian footballer
Juan Diego Gonzalez-Vigil (born 1985), Peruvian footballer
Juan Diego Madrigal (born 1986), Costa Rican footballer
Juan Diego Ramírez (born 1971), road cyclist from Colombia
Juan Diego Solanas (born 1966), Argentine film director
Saint Juan Diego (1474–1548), the first indigenous American saint
Juan Diego Ramirez (officer) (1710–1737), officer in the Spanish-Portuguese War


Masefield may refer to:
Places
 Masefield, Saskatchewan
People
 John Masefield (1878-1967), English poet
 Paul Masefield (b. 1970), English footballer


Madathilparampil Mammen Thomas (1916—1996) was an Indian Christian theologian, social thinker, and activist. He served as Governor of the Indian State, Nagaland (1990–1992), and as the Chairperson of the Central Committee of World Council of Churches (1968–1975).

Biography
Thomas was born on 15 May 1916 at Kozhenchery, Kerala India. His father Madathilparampil Mammen was a reformation leader, printer and publisher based in Kozhenchery, Kerala, and was involved in the Independence Movement in India during the Salt Satygraha. His mother was Ooriapadickal Mariamma, a school teacher. He was the eldest of nine children.

Thomas was raised in a Mar Thoma Syrian Church, in which his father was well known evangelist. In 1931, Thomas went to study Chemistry in a college in Trivandrum, Kerala, and had an evangelical spiritual experience. As a consequence, he became active in the Mar Thoma Youth Union and the Student Christian Movement, and became involved in evangelism among low-caste youth. Soon after obtaining his degree in 1935, he accepted the post of a teacher at Ashramam High School, Perumbavoor, run by the Mar Thoma Church, where the teachers used to pay part of their meager salary to the students from poor families. In 1937, instead of taking a lucrative job he went to Trivandrum, the capital of Kerala and started an orphanage there.

Thomas was the first full-time organizing secretary of Yuvajana Sakhyam (the Youth wing of the Mar Thoma Church) from 1945-47. He applied for ordination in the Mar Thoma Church, but that was rejected because of his membership in Communist party. At the same time he was rejected by the communist party because of his faith.

Thomas became known for his ecumenical work, first being on staff with the World Student Christian Federation in Geneva (1947-1953), then serving as a moderator of the Central committee of the World Council of Churches (1968-1975).

In 1990 he was appointed as Governor of Nagaland, a state with a large number of Christians, but later resigned in 1992.

He was conferred with the honorary doctorate degree by the University of Uppsala in 1978. He was living at Manjadi, Tiruvalla. He died on 3 December 1996 and was laid to rest at Tiruvalla, Kerala.

Works
The acknowledged Christ of the Indian Renaissance (1969 SCM Press, London)
Risking Christ for Christ's Sake
Nagas towards 2000
My Ecumenical Journey 1947-75 (1990)
Response to Tyranny

References

Further reading

External links

1910 births
1996 deaths
People from Thiruvalla
Saint Thomas Christians
Indian Christian theologians
Governors of Nagaland
Christian communists
Christian and Hindu interfaith dialogue


Caloptilia azaleella (azalea leaf miner) is a moth of the family Gracillariidae. It is endemic to Japan, but has been introduced worldwide, wherever there are Azaleas.

Distribution
Initially described in the Netherlands from plants imported from Japan, it is found throughout Europe and has also been introduced to New Zealand and eastern Australia. In the southern part of Britain it occurs in sheltered gardens including Buckingham Palace, the Royal Botanic Gardens, Kew and the Royal Horticultural Society Gardens, Wisley. It has been widely reported in greenhouses. In the United States the species can be found from Florida to Texas, and as far north as Long Island, West Virginia, and the Ohio Valley. On the west coast it is found in California, Washington and British Columbia, Canada.

Description
The type locality is from Boskoop, Netherlands, and was described in 1913, from moths reared on Azalea indica, a cultivar of Rhododendron indicum, which was imported from Japan. The moths forewings are mainly dark-brown with a yellow band along the costal margin. The wingspan is  and it flies from May to October depending on location and in Britain is double-brooded and sometimes there is a partial third brood.

Ecology
Caloptilia azaleella deposits its eggs on azalea (Rhododendron spp) plants, under leaves near the midrib. Thiese are the only hosts so far recorded. The larva initially forms a mine and later rolls the leaf downwards from the tip, forming a cone. When mature a pale-brown pupa is formed in a white, membranous silken cocoon spun beneath a leaf and the moths can mate a week later.

References

External links

 Lepiforum
 Azalea Leaf Miner at UKmoths

azaleella
Leaf miners
Moths described in 1913
Endemic insects of Japan
Moths of Africa
Moths of Asia
Moths of Australia
Moths of Europe
Moths of Japan
Moths of New Zealand
Moths of North America


On 14 March 1961 an aircraft accident occurred near Yuba City, California. A United States Air Force B-52F-70-BW Stratofortress bomber, AF Serial No. 57-0166, c/n 464155, carrying two nuclear weapons departed from Mather Air Force Base near Sacramento. According to the official Air Force report, the aircraft experienced an uncontrolled decompression that required it to descend to  in order to lower the cabin altitude. Increased fuel consumption caused by having to fly at lower altitude, combined with the inability to rendezvous with a tanker in time caused the aircraft to run out of fuel. The aircrew ejected safely, and the now uncrewed aircraft crashed  west of Yuba City, tearing the nuclear weapons from the aircraft on impact. The weapons did not detonate, as their safety devices worked properly. A fireman was killed and several others injured in a road accident while en route to the accident scene.

Timeline

The following timeline is an abridged version of the description transcribed by Oskins and Maggelet from a declassified copy of the original Air Force accident report. Doe 11 was the aircraft call sign. Doe 13 was a second B-52 in formation for the first portion of the flight.

All times are hours and minutes after takeoff.

0:20  –  the pilot first noticed excessive hot air coming from the pilots' vents. All attempts to control this hot air were unsuccessful.

6:00  –  Mather Command Post contacted the aircraft on HF radio. The heat problem was discussed and wing guidance received. This consisted of several suggested corrective actions which were verified by the pilot as having been used earlier without success.

6:30  – Mather control room called the aircraft on HF radio and discussed the heat problem and the effects of the heat on the aircraft electronics and crew personnel. Wing guidance at this time was to continue the mission.

6:50  –  Mather control room contacted the aircraft and Wing guidance was to "continue mission as long as you can; call us back after second refueling tonight and advise us of your status, if it gets intolerable, of course, bring it home."

11:15  –  Mather control called Doe 11 to see if he would complete the mission. At that the response was, "We are going to try."

12:35  –  Mather control was contacted by Doe 11 and told that Doe 13's refueling was completed and "we are about ready to take off."  Control asked, "Your present status . . . has it improved?"  The pilot answered "Negative . . . worse . . . number 3 engine setting at 70% . . . we had it once before and it cleared up but at this time it has not cleared as yet."  Control advised, "Understand you will proceed on course and we will be looking for you tomorrow."

14:00  –  the outside panel of the pilot's L-4 window shattered. The heat in the cockpit was unbearable at this time and had cracked the glass case for the ball on both pilot's and co-pilot's turn and slip indicators. It is estimated that the upper compartment heat level ranged from  or higher during this period. A decision was made to depressurize the aircraft and attempt to continue the mission. Altitude was .

14:20  –  after 20 minutes of unpressurized flight, the decision was made to descend to  and continue the mission as far as possible at this altitude.

15:00  –  Mather control contacted Doe 11 and asked "Which windshield is cracked and what is your present altitude?"  Answer received, "The L-4 window shattered, heat unbearable at altitude, two sick crew members. We have descended to  and plan to go  north of TP 3.19 and return direct to Mather."  They were advised to "proceed as planned, recommend you stay low altitude, give us an estimate on your fuel as soon as you get in close enough to contact us."

16:50  –  Mather control contacted Doe 11 via HF radio requesting ETA to Mather. The aircraft reported, "We just passed TP 3.19 at 1212Z, estimate  north of TP 3.19 at 1239Z, ETA to Mather 1755Z."

18:50  –  Mather control contacted the aircraft through HF radio to check his progress.

19:45  –  McClellan called for flight plan and altitude required from last position to Mather.

20:30  –  aircraft contacted McClellan to ask Early Warning vessel "Hardware" to look out for them and would like a fix.

21:00  –  the aircraft contacted Mather control stating, "We would like a tanker up here and get a little fuel. We now figure we will be over the field at . That is a little light. We would like to have a tanker."  And, control answered Doe 11 "will be cleared for a straight in approach and will have tanker standby . . . we will not launch unless you go below ."

Doe 11's ETA to Mather at this time was given as approximately 22:30 hours after takeoff.

For approximately the next hour, several heading deviations up to 30 degrees were made by the pilot of Doe 11 to circumnavigate the weather associated with a front in this area. Turbulence was moderate. It is estimated from study of weather and Doe 11 pilot and navigator interviews that 7 or 8 minutes were lost during this frontal penetration due to these heading deviations.

21:50  –  Mather was contacted through HF radio and advised he had, "#1 main tank gauge stuck at  . . . we are not sure just how much fuel we have in it now. We have No. 2 and one other 1/4 full warning light on and I think it would be a good idea to get that tanker airborne."  Mather Control Room advised, "We have a tanker airborne. Pick him up at Red Bluff VOR and refuel back in this direction. You might keep in mind, if things get a little close up there, head into Beale AFB."  Later in this same conversation, Mather control indicated, "We will get it off the ground here ASAP."

22:10  –  Democrat contacted the aircraft on HF advising, "McClellan is requesting your present position."  The aircraft advised, " . . . just coasted in and looking for our tanker."  This was the last contact through Democrat HF radio.

22:10  –  the tanker was launched.

22:23  –  the bomber and the tanker initiated the head on rendezvous at . Normal mileage countdown was used and the bomber turned the tanker at . This left Doe 11 flying at  IAS approximately  behind the tanker after the tanker rolled out on refueling track. The bomber asked the tanker to slow down. The tanker reduced speed to  IAS, and then to  IAS. The bomber maintained  IAS to approximately  behind this tanker, and then lost power. The pilot had warned the crew earlier of the possibility of bailout and he now alerted them to prepare for bailout. He initiated a 30-degree bank to the west toward a clear area as all engines flamed out together at approximately 22:40 hours after takeoff.

The bailout sequence began at approximately  with an outside temperature of approximately , and was normal except the gunner could not jettison his turret despite full strength pull on the inner emergency release handle. The gunner was called forward and bailed out the navigator hatch, using the spare chute in the forward compartment. The pilot continued to guide the aircraft toward a clear area. The crew continued to bail out in order of navigator, spare navigator, spare pilot, EW, gunner, co-pilot and radar navigator. The pilot bailed out at . The aircraft was trimmed and calculated to be at approximately a 21:1 glide ratio at this time. The aircraft made one complete 360-degree left turn and crashed into a clear flat barley field area  west of Yuba County Airport, California, at approximately 22:50 after takeoff. The aircraft struck the ground at a 15.3-degree left bank and an estimated attitude of 5 degrees nose down at an indicated airspeed of approximately . Impact angle was approximately 45 degrees.

Book
In a 2012 book, lieutenant colonel Earl McGill, a retired Strategic Air Command B-52 pilot, claims that the aircrew, after an inflight refueling session that provided inadequate fuel, refused the offer of an additional, unscheduled inflight refueling, bypassed possible emergency landing fields, and ran out of fuel. McGill, based on his experience, blames the aircrew failures on the use of dexedrine to overcome tiredness on the 24-hour flight preceding the accident.

See also

 List of accidents and incidents involving military aircraft

Notes

References

1961 in military history
Aviation accidents and incidents involving nuclear weapons
History of Sutter County, California
Aviation accidents and incidents in the United States in 1961
Aviation accidents and incidents in California
20th-century military history of the United States
Decompression accidents and incidents
Accidents and incidents involving the Boeing B-52 Stratofortress
Aviation accidents and incidents caused by fuel exhaustion
Yuba City B-52 crash
March 1961 events in the United States
Nuclear accidents and incidents in the United States


Durch fremde Hand is the ninth studio album by L'Âme Immortelle.  The album is featured on two CDs and is the twin album of the band's previous studio album, Namenlos.  The first disc contains remix versions of the songs on the first disc of Namenlos.  A limited edition digipack, limited to 2,000 copies worldwide, was also released containing a 28-page booklet featuring artwork and song lyrics.

Track listing

Disc 1

 "Vergessen" (Die Namenlosen von Berlin by Üebermutter) – (2:15)
 "1000 Voices" (Echoes of a Thousand Voices Covered by ASP) – (5:10)
 "Behind the Light" (Beautiful Light Remix by Bella Donna) – (4:11)
 "Bleib" (Plastic Remix by Dope Stars Inc.) – (3:55)
 "Requiem" (Satya Yuga Remix by Affentanz) – (4:30)
 "Lost" (Pin-Up Remix by XPQ-21) – (3:02)
 "Blutrot" (Quiet Heart Remix by Necessary Response) – (4:45)
 "Reborn" (Hardcore Remix by Las Vegas 909) – (5:33)
 "Es Tut Mir Leid" (Entschuldigung Remix by Grendel) – (5:04)
 "Niemals" (Club Remix by Wynardtage) – (4:54)
 "Jenseits der Schatten" (Void Remix by Monozelle) – (4:52)
 "The Cleansing" (Voidian Cleansing Remix by Beyond the Void) – (3:42)
 "Namenlos" (Drifting Downwards Remix by Perfidious Words) – (5:31)

Disc 2

 Ophelia – (1:55)
 Ein Blick Zurück – (4:12)
 Suffocating Endlessly – (4:20)
 Now You’re Gone – (3:53)
 Durch Fremde Hand – (4:29)
 Das Kühle Grab – (2:53)

References

2008 albums


Kiefer-Stewart Co. v. Seagram & Sons, Inc., 340 U.S. 211 (1951), was a decision by the United States Supreme Court, which held that an agreement among competitors in interstate commerce to fix maximum resale prices of their products violates the Sherman Antitrust Act.

Background
The petitioner, Kiefer-Stewart Company, was an Indiana drug concern which does a wholesale liquor business. Respondents, Seagram and Calvert corporations, are affiliated companies that sell liquor in interstate commerce to Indiana wholesalers. Kiefer-Stewart brought this action in a federal district court for treble damages under the Sherman Act,  and . The complaint charged that respondents had agreed or conspired to sell liquor only to those Indiana wholesalers who would resell at prices fixed by Seagram and Calvert, and that this agreement deprived Kiefer-Stewart of a continuing supply of liquor, to its great damage.

On the trial, evidence was introduced tending to show that Seagram had fixed maximum prices above which the wholesalers could not resell. The jury returned a verdict for petitioner, and damages were awarded. The United States Court of Appeals for the Seventh Circuit reversed. It held that an agreement among respondents to fix maximum resale prices did not violate the Sherman Act, because such prices promoted, rather than restrained, competition. It also held the evidence insufficient to show that respondents had acted in concert. Doubt as to the correctness of the decision on questions important in antitrust litigation prompted the Supreme Court to grant certiorari.

Holding
The Supreme Court ruled that the Court of Appeals erred in holding that an agreement among competitors to fix maximum resale prices of their products does not violate the Sherman Act. For such agreements, no less than those to fix minimum prices, cripple the freedom of traders, and thereby restrain their ability to sell in accordance with their own judgment. The Supreme Court reaffirmed United States v. Socony-Vacuum Oil Co. (1940):

See also
List of United States Supreme Court cases, volume 340
Albrecht v. Herald Co. (1968)

References

Further reading

External links

United States Supreme Court cases
United States Supreme Court cases of the Vinson Court
United States antitrust case law
1951 in United States case law
Seagram


This is a list of the members of the Australian House of Representatives in the 13th Australian Parliament, which was elected at the 1931 election on 19 December 1931. The incumbent Australian Labor Party led by Prime Minister of Australia James Scullin was defeated by the newly formed opposition United Australia Party (descended from the Nationalist Party of Australia) led by ex-Labor Joseph Lyons with coalition partner the Country Party led by Earle Page.

Notes

References

Members of Australian parliaments by term
20th-century Australian politicians


Pete Sampras defeated Jim Courier in the final, 3–6, 7–6(7–5), 6–3, 6–4 to win the singles title at the 1991 ATP Tour World Championships. It was his first Tour Finals title.

Andre Agassi was the defending champion, but was defeated by Courier in the semifinals.

Draw

Finals

Ilie Năstase group
Standings are determined by: 1. number of wins; 2. number of matches; 3. in two-players-ties, head-to-head records; 4. in three-players-ties, percentage of sets won, or of games won; 5. steering-committee decision.

John Newcombe group
Standings are determined by: 1. number of wins; 2. number of matches; 3. in two-players-ties, head-to-head records; 4. in three-players-ties, percentage of sets won, or of games won; 5. steering-committee decision.

See also
 ATP World Tour Finals appearances

References
 ATP Tour World Championships draw

Singles
Tennis tournaments in Germany
1991 in German tennis
Sports competitions in Frankfurt


Amthamine is a histamine agonist selective for the H2 subtype. It has been used in vitro and in vivo to study gastric secretion, as well as other functions of the H2 receptor.

References

Histamine agonists
Thiazoles


Moonshine is a suburb of Upper Hutt in the lower (southern) North Island of New Zealand. It comprises a rural area located northwest of urban Upper Hutt and south of Paekākāriki.

References

Suburbs of Upper Hutt


Histamine trifluoromethyl toluidide (HTFMT) is a mixed H1/H2 histamine agonist which is significantly more potent than histamine itself.

It also produces additional actions which appear to be independent of histamine receptors.

References

Histamine agonists
Imidazoles
Trifluoromethyl compounds


Proxyfan is a histamine H3 receptor ligand which is a "protean agonist", producing different effects ranging from full agonist, to antagonist, to inverse agonist in different tissues, depending on the level of constitutive activity of the histamine H3 receptor. This gives it a complex activity profile in vivo which has proven useful for scientific research.

References

Ethers
Histamine agonists
Imidazoles


Methimepip is a histamine agonist which is highly selective for the H3 subtype. It is the N-methyl derivative of immepip.

References

Imidazoles
Histamine agonists
Piperidines


Immethridine is a histamine agonist selective for the H3 subtype.

References

Histamine agonists
Imidazoles
4-Pyridyl compounds


VUF-8430 is a histamine agonist selective for the H4 subtype.

References

Histamine agonists
Guanidines
Thioureas


Nasty, Live & Funky is a live album released by the funk/R&B group Cameo in 2007. In addition to the live material, two studio tracks were included: "Come Fly With Me", and "Nasty", both written by Larry Blackmon. The "Mega-Mix" is a remix of the album's live tracks. This album is a track for track re-release of Nasty from 1996, but with a new album title and cover.

Track listing
 "Intro" – 1:03
 "Flirt" – 1:36 - Blackmon, Jenkins
 "She's Strange" – 2:37 - Blackmon, Jenkins, Leftenant, Singleton
 "Back and Forth" – 5:54 - Blackmon, Jenkins, Kendrick, Leftenant
 "Skin I'm In" – 5:09 - Blackmon
 "Why Have I Lost You" – 6:10 - Blackmon
 "Sparkle" – 4:23 - Blackmon, Lockett
 "Candy" – 4:45 - Blackmon, Jenkins
 "Shake Your Pants" (Intro) – 0:42
 "Shake Your Pants" – 4:00 - Blackmon
 "I Just Want to Be" – 1:38 - Blackmon, Johnson
 "Keep It Hot" – 5:12 - Blackmon, Lockett
 "Word Up!" – 6:44 - Blackmon, Jenkins
 "Come Fly With Me" – 3:57 - Blackmon
 "Nasty" – 3:44 - Blackmon
 "Megamix" – 6:29 - Cameo

References

Cameo (band) albums
2007 live albums


SCH-79687 is a histamine antagonist selective for the H3 subtype.

References

Chloroarenes
H3 receptor antagonists
Imidazoles
Ureas


NNC 38-1049 is a histamine antagonist selective for the H3 subtype. It has anorectic effects in animal studies and is being researched as a potential treatment for obesity.

References

Carboxamides
Aromatic ketones
Chloroarenes
H3 receptor antagonists
Piperazines
Cyclopentanes


JNJ-5207852 is a histamine antagonist selective for the H3 subtype. It has stimulant and nootropic effects in animal studies, and has been suggested as a possible treatment for some memory defects associated with epilepsy. JNJ-5207852 itself did not progress to clinical development due to poor pharmacokinetic characteristics, but the related compound JNJ-17216498 was in a Phase II clinical trial for the treatment of narcolepsy in 2007.

References

H3 receptor antagonists
Johnson & Johnson brands
Phenol ethers
1-Piperidinyl compounds


A cannabinoid receptor antagonist, also known simply as a cannabinoid antagonist or as an anticannabinoid, is a type of cannabinoidergic drug that binds to cannabinoid receptors (CBR) and prevents their activation by endocannabinoids. They include antagonists, inverse agonists, and antibodies of CBRs. The discovery of the endocannabinoid system led to the development of CB1 receptor antagonists. The first CBR inverse agonist, rimonabant, was described in 1994. Rimonabant blocks the CB1 receptor selectively and has been shown to decrease food intake and regulate body-weight gain. The prevalence of obesity worldwide is increasing dramatically and has a great impact on public health. The lack of efficient and well-tolerated drugs to cure obesity has led to an increased interest  in research and development of CBR antagonists. Cannabidiol (CBD), a naturally occurring cannabinoid and a non-competitive CB1/CB2 receptor antagonist, as well as Δ9-tetrahydrocannabivarin (THCV), a naturally occurring cannabinoid, modulate the effects of THC via direct blockade of cannabinoid CB1 receptors, thus behaving like first-generation CB1 receptor inverse agonists, such as rimonabant. CBD is a very low-affinity CB1 ligand, that can nevertheless affect CB1 receptor activity in vivo in an indirect manner, while THCV is a high-affinity CB1 receptor ligand and potent antagonist in vitro and yet only occasionally produces effects in vivo resulting from CB1 receptor antagonism. THCV has also high affinity for CB2 receptors and signals as a partial agonist, differing from both CBD and rimonabant.

History

For centuries hashish and marijuana from the Indian hemp Cannabis sativa L. have been used for medicinal and recreational purposes. In 1840, Schlesinger S. was apparently the first investigator to obtain an active extract from the leaves and flowers of hemp. A few years later, in 1848, Decourtive E. described the preparation of an ethanol extract that on evaporation of the solvent gave a dark resin, which he named “cannabin”. In 1964 the main active constituent of C. sativa L., Δ9-tetrahydrocannabinol (THC), was isolated and synthesized by Mechoulam's laboratory. Two types of cannabinoid receptors, CB1 and CB2, responsible for the effects of THC were discovered and cloned in the early 1990s. Once cannabinoid receptors had been discovered, it became important to establish whether their agonists occur naturally in the body. This search led to the discovery of the first endogenous cannabinoid (endocannabinoid), anandamide (arachidonoyl ethanolamide). Later on other endocannabinoids were found, for example 2-AG (2-arachidonoyl glycerol). These findings raised further questions about the pharmacological and physiological role of the cannabinoid system. This revived the research on cannabinoid receptor antagonists which were expected to help answer these questions. The use of the cannabinoid agonist, THC, in its many preparations to enhance appetite is a well known fact. This fact led to the logical extension that blocking of the cannabinoid receptors might be useful in decreasing appetite and food intake. It was then discovered that the blockage of the CB1 receptor represented a new pharmacological target. The first specific CB1 receptor antagonist / inverse agonist was rimonabant, discovered in 1994.

Endocannabinoids and their signaling system
The endogenous cannabinoid system includes cannabinoid receptors, their endogenous ligands (endocannabinoids) and enzymes for their synthesis and degradation.

There are two main receptor types associated with the endocannabinoid signaling system: cannabinoid receptor 1 (CB1) and 2 (CB2). Both receptors are 7-transmembrane G-protein coupled receptors (GPCRs) which inhibit the accumulation of cyclic adenosine monophosphate within cells. CB1 receptors are present in highest concentration in the brain but can also be found in the periphery. CB2 receptors are mostly located in the immune and haematopoietic systems.

Endocannabinoids are eicosanoids acting as agonists for cannabinoid receptors, and they occur naturally in the body. Cannabinoid receptor-related processes are, for example, involved in cognition; memory; anxiety; control of appetite; emesis; motor behavior; sensory, autonomic, neuroendocrine, and immune responses; and inflammatory effects.
There are two well-characterized endocannabinoids located in the brain and periphery. The first identified was anandamide (arachidonoyl ethanolamide), and the second was 2-AG (2-arachidonoyl glycerol). Additional endocannabinoids include virodhamine (O-arachidonoyl ethanolamine), noladin ether (2-arachidonoyl glyceryl ether) and NADA (N-arachidonoyl dopamine).

Mechanism of action

CB1 receptors are coupled through Gi/o proteins and inhibit adenylyl cyclase and activate mitogen-activated protein (MAP) kinase. In addition, CB1 receptors inhibit presynaptic N- and P/Q-type calcium channels and activate inwardly rectifying potassium channels. CB1 antagonists produce inverse cannabimimetic effects that are opposite in direction from those produced by agonists for these receptors.

CB1 receptors are highly expressed in hypothalamic areas which are involved in central food intake control and feeding behavior. This strongly indicates that the cannabinoid system is directly involved in feeding regulation. These regions are also interconnected with the mesolimbic dopamine pathway, the so-called "reward" system. Therefore, CB1 antagonists might indirectly inhibit the dopamine-mediated rewarding properties of food. Peripheral CB1 receptors are located in the gastrointestinal (GI) tract, liver and in adipose tissue. In the GI, CB1 receptors are located on nerve terminals in the intestines. Endocannabinoids act at the CB1 receptors to increase hunger and promote feeding and it is speculated that they decrease intestinal peristalsis and gastric emptying. Thus, antagonism at these receptors can inverse these effects. Also, in peripheral tissues, antagonism of CB1 receptors increases insulin sensitivity and oxidation of fatty acids in muscles and the liver. A hypothetical scheme for the metabolic effects of CB1 receptor antagonists is shown in Figure 1.

Drug design
The first approach to develop cannabinoid antagonists in the late 1980s was to modify the structure of THC, but the results were disappointing. In the early 1990s new family of cannabinoid agonists was discovered from the NSAID (non-steroidal anti-inflammatory) drug pravadoline which led to the discovery of aminoalkyl indole antagonists with some but limited success.  As the search based on the structure of agonists was disappointing it was no surprise that the first potent and selective cannabinoid antagonist belonged to an entirely new chemical family. In 1994 the first selective cannabinoid antagonist,  SR141716 (rimonabant), was introduced by Sanofi belonging to a family of 1,5-diarylpyrazoles.

Rimonabant

Rimonabant, also known by the systematic name [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride)], is a 1,5-diarylpyrazole CB1 receptor antagonist (Figure 2). Rimonabant is not only a potent and highly selective ligand of the CB1 receptor, but it is also orally active and antagonizes most of the effects of cannabinoid agonists, such as THC, both in vitro and in vivo. Rimonabant has shown clear clinical efficacy for the treatment of obesity.

Binding
Binding of an agonist ligand to the CB1 receptor provokes a conformational change and leads to the active state of the receptor which is responsible for the signal transduction. However, there is an additional mechanism that can lead to the active state in the absence of ligand. As numerous other GPCRs, CB1 receptor displays a high level of constitutive activity and thus it can spontaneously adopt an active conformational state in the absence of agonist binding, keeping elevated basal levels of intracellular signaling. This can be explained by the two state-model of receptor activation in which receptors are in equilibrium between two states, active and inactive (R* and R). An agonist will stabilize the active state leading to activation, a neutral antagonist binds equally to active and inactive states, whereas an inverse agonist will preferentially stabilize the inactive state (Figure 3).

Rimonabant has been reported in many cases to behave as an inverse agonist rather than as a neutral antagonist and it is likely that it binds preferentially to the inactive state of the CB1, thereby decreasing the activation of the signaling pathway. The key binding interaction is a hydrogen bond formed between the carbonyl group of rimonabant and the Lys192 residue of the CB1 receptor. This bond stabilizes the Lys192-Asp366 salt bridge of the intracellular end of transmembrane helices 3 and 6 (Figure 4). This specific salt bridge is present in the inactive state of the receptor but absent in the active state.

In the inactive state of CB1 rimonabant binds within the transmembrane-3-4-5-6 aromatic microdomain. The binding of rimonabant involves direct aromatic stacking interactions between its 2,4-dichlorophenyl ring and the Trp279/Phe200/Trp356 residues on the one side and the para-chlorophenyl ring and the Tyr275/Trp255/Phe278 residues on the other side. The lipophilic piperidinyl moiety fits nicely in a cavity formed by the amino acid residues Val196/Phe170/Leu387 and Met384 (Figure 4).

Pharmacophore
Most CB1 antagonists reported so far are close analogs or isosteres of rimonabant. A general CB1 inverse agonist pharmacophore model can be extracted from the common features of these analogs, diarylpyrazoles (Figure 4). This pharmacophore contains a cyclic core, C, (e.g. pyrazole in rimonabant) substituted by two aromatic moieties, A and B. A hydrogen bond acceptor unit, D, connects C with a cyclic lipophilic part, E. In some cases unit E directly connects to C. In Figure 4 rimonabant is used as an example. Unit A represents a 4-chlorophenyl group and unit B a 2,4-dichlorophenyl ring. Unit C is the central pyrazole ring and unit D represents the carbonyl group which serves as the hydrogen bond acceptor. Unit E represents a lipophilic aminopiperidinyl moiety.

Structure-activity relationships
Optimal binding at the CB1 receptor requires a para-substituted phenyl ring at the pyrazole 5-position. The 5-substituent of the pyrazole is involved in receptor recognition and antagonism. The para-substituent of the phenyl ring could be chlorine, bromine or iodine, but it has been shown that an alkyl chain could also be tolerated. Numbering of the central pyrazole ring is shown in Figure 2.

A 2,4-dichloro-substituted phenyl ring at the pyrazole 1-position is preferred for affinity as well as for the activity. It has been shown that additional halogens on this phenyl ring decrease affinity.

It is also favorable to have a ring substitution at the 3-carboxamide group, such as the 1-piperidinyl group in rimonabant. Replacement of the amino piperidinyl substituent by alkyl amides, ethers, ketones, alcohols or alkanes resulted mostly in decreased affinity. Replacement of the piperidinyl by pentyl or a heptyl chain gave the compounds agonistic properties. Based on these results it was concluded that the pyrazole 3-position seems to be involved in agonism, while the 1-,4-,5-positions appear to be involved in antagonism.

Research has shown that the absence of the carboxamide oxygen results in decreased affinity. Furthermore, the presence of carboxamide oxygen contributes in conferring the inverse agonist properties, whereas analogs lacking this oxygen are found to be neutral antagonists. These results support the hypothesis that the carboxamide oxygen forms a hydrogen bond with Lys192 residue at the CB1 receptor.

Diarylpyrazole derivatives
SR141716 (rimonabant) analogs have recently been described by several groups, leading to a good understanding of the structure-activity relationship (SAR) within this chemical group. While most compounds described are less potent than SR141716, two of them are worth mentioning, SR147778 and AM251, although both may have action at mu opioid receptors as well.

SR147778 (surinabant), a second generation antagonist, has a longer duration of action than rimonabant and enhanced oral activity. This enhanced duration of action is probably due to the presence of the more metabolically stable ethyl group at the 4-position of its pyrazole ring. Another change is the replacement of the 5-phenyl chlorine substituent by bromine.

The diarylpyrazole derivative, AM251, has been described where chlorine substituent has been replaced by iodine in the para position of the 5-phenyl ring. This derivative appeared to be more potent and selective than rimonabant.

21 analogs possessing either an alkyl amide or an alkyl hydrazide of variant lengths in position 3 were synthesized. It was observed that affinity increases with increased carbon chain length up to five carbons. Also the amide analogs exhibited higher affinity than hydrazide analogs. However, none of these analogs possessed significantly greater affinity than rimonabant but nevertheless, they were slightly more selective than rimonabant for the CB1 receptor over the CB2 receptor.

Several attempts have been made to increase the affinity of the diarylpyrazole derivatives by rigidifying the structure of rimonabant. In terms of the general pharmacophore model the units A, B and/or C are connected by additional bonds leading to rigid molecules. For example, the condensed polycyclic pyrazole NESS-0327 showed 5000 times more affinity for the CB1 receptor than rimonabant. However, this compound possesses a poor central bioavailability.

Another compound, the indazole derivative O-1248, can be regarded as an analog of rimonabant wherein its 5-aryl group is fused to the pyrazole moiety. However, this structural modification resulted in a 67-fold decrease in CB1 receptor affinity.

These diarylpyrazole derivatives of rimonabant are summarized in Table 1.

Other derivatives
Structurally different from the 1,5-diarylpyrazoles are the chemical series of the 3,4-diarylpyrazolines. Within this series is SLV-319 (ibipinabant), a potent CB1 antagonist which is about 1000-fold more selective for CB1 compared with CB2 and displays in vivo activity similar to rimonabant.

Another approach used to develop analogs of rimonabant was to replace central pyrazole ring by another heterocycle. An example of this approach are 4,5-diarylimidazoles and 1,5-diarylpyrrole-3-carboxamides.

A large number of fused bicyclic derivatives of diaryl-pyrazole and imidazoles have been reported. An example of these is a purine derivative where a pyrimidine ring is fused to an imidazole ring. Otenabant (CP-945,598) is an example of a fused bicyclic derivative developed by Pfizer.

Several research groups have studied six-membered ring pyrazole bioisosteres. For example, one 2,3-diarylpyridine derivative was shown to be potent and selective CB1 inverse agonist. The structure of this compound demonstrates the possibility that the amide moiety of rimonabant could be split into a lipophilic (benzyloxy) and a polar (nitrile) functionality. Other six-membered ring analogs are for example pyrimidines and pyrazines.

In addition to the five and six-membered ring analogs there are other cyclic derivatives such as the azetidines. One example is the methylsulfonamide azetidine derivative which has a 1,1-diaryl group that mimics the 1,5-diaryl moiety of the diarylpyrazoles. The sulfonyl group serves as a hydrogen bond acceptor. The 1,1-diaryl group is also present in derivatives such as the benzodioxoles and hydantoins.

Acyclic analogs have also been reported. These analogs contain a 1,2-diaryl motif which corresponds to the 1,5-diaryl substituents of rimonabant. An example of an acyclic analog is taranabant (MK-0364) developed by Merck.

Determination of crystal structures of CB1 and CB2 receptors facilitated the design of structurally different CBR antagonists.

Representatives of these analogs are summarized in Table 2.

CB1 receptor antibodies
Antibodies against the CB1 receptor have been developed and introduced into clinical use in Russia. They include brizantin (®) and dietressa (®). Brizantin is indicated for the treatment of nicotine withdrawal and smoking cessation and dietressa is indicated for weight loss. Dietressa is available over-the-counter in Russia.

Current status
Rimonabant (Acomplia) has been approved in the European Union (EU) since June 2006 for the treatment of obesity. On 23 October 2008 the European Medicines Agency (EMEA) has recommended the suspension of the marketing authorization across the EU for Acomplia from Sanofi-Aventis based on the risk of serious psychiatric disorders. On 5 November 2008 Sanofi-Aventis announced discontinuation of rimonabant clinical development program.

Sanofi-Aventis has also discontinued development of surinabant (SR147778), a CB1 receptor antagonist for smoking cessation (31 October 2008).

Merck has stated in its press release on 2 October 2008 that they will not seek regulatory approval for taranabant (MK-0364) to treat obesity and will discontinue its Phase III clinical development program. Data from Phase III clinical trial showed that greater efficacy and more adverse effects were associated with the higher doses of taranabant and it was determined that the overall profile of taranabant does not support further development for obesity.

Another pharmaceutical company, Pfizer, terminated the Phase III development program for its obesity compound otenabant (CP-945,598), a selective antagonist of the CB1 receptor. According to Pfizer their decision was based on changing regulatory perspectives on the risk/benefit profile of the CB1 class and likely new regulatory requirements for approval.

A number of initiatives have been published to develop CB1 antagonists that target only peripheral CB1 receptors by restricting their ability to cross the blood brain barrier. Among these initiatives 7TM Pharma has reported the development of TM38837.
A review has now published on the approaches and compounds being pursued as peripherally restricted CB1 receptor blockers.

See also
 Endocannabinoid enhancer
 Endocannabinoid reuptake inhibitor

References

Drug discovery


Sir William Purdie Treloar, 1st Baronet (13 January 1843 – 6 September 1923) was an English businessman who was Sheriff of London in 1889–1900 and Lord Mayor of London in 1906–1907. He established an active "Cripples' Fund" as his mayoral appeal.

Career
Treloar was born in London, and educated at King's College School. He was head of the firm of Treloar and Sons (haberdashery), and Director and Trustee of T. Cook and Son. He was selected an Alderman of the City of London for the Ward of Farringdon Without from 1892, a Sheriff of the City of London in 1899 and Lord Mayor of the City of London in 1906–1907.

On St Thomas's Day, 21 December 1881, he became a Common Councilman for the Ward of Farringdon Without. He served as a Common Councilman until he became its Alderman in 1892. As Alderman of the Ward it is said that one represents the World, the Flesh and the Devil i. e., Fleet Street, the home of the newspaper press; the Central Meat Market; and the Temple.

He was the author of A Lord Mayor's Diary 1906-7 (1920) and of the earlier works Ludgate Hill: Past and Present (1881, 2nd ed 1892), Prince of Palms (1884), With the Kaiser in the East, 1898 (1915) and Wilkes and the City (1917).

Lord Mayor of London
Sir William Treloar established a "Cripples' Fund" as his mayoral appeal, for which he gained 10,000 pounds of donations for his Alton Hospital during his tenure as Lord Mayor of London 9 November 1906 to 1907. Sir William and Lady Treloar greeted their first patients at Alton railway station on 8 September 1908 and a new branch was opened at Sandy Point, Hayling Island, in September 1919, with 50 patients.

As a result of this in 1908 he opened Treloar College and Treloar School, near Alton, Hampshire, which has become part of the Treloar Trust a charity supporting the UK's leading specialist centre providing education, independence training and opportunities for young people with physical disabilities.

Treloar maintains its links with The City and Livery Companies: each Lord Mayor of the City of London automatically becomes a trustee of Treloar Trust and visits the college and school.

During his period of office as Lord Mayor he made a ceremonial visit to Cornwall, the county from which his ancestors came. He received the Freedom of Helston at Helston Guildhall and had the honour of leading the full dress Furry Dance at noon on 8 May 1907.

Honours

He was knighted by Queen Victoria on 29 March 1900 at Windsor Castle as a Knight bachelor. On 8 May 1907 he was in Helston, Cornwall "the home of my fathers" and was given the Freedom of the Borough of Helston and then Freedom of the Borough of Truro. On 8 July 1907, Treloar conducted the opening of Simmons Park in Okehampton, Devon. After this date, a Swiss-style chalet – named Chalet Treloar – was built by the riverside in his honour. On 17 July 1907 he was created a baronet, of Grange Mount in the Parish of All Saints, Upper Norwood, in the Borough of Croydon.

Sir William died at his home Grange Mount, in Upper Norwood on 6 September 1923 aged 80 and was buried alongside his wife at Shirley, Surrey.

References

Further reading
 Lawrence, C. E. (1925) William Purdie Treloar. A Monograph, London: John Murray

External links
Treloar Trust official page
Portraits of Sir William P. Treloar in the National Portrait Gallery.

|-

1843 births
1923 deaths
People educated at King's College School, London
Baronets in the Baronetage of the United Kingdom
Sheriffs of the City of London
20th-century lord mayors of London
20th-century English politicians
19th-century English politicians
Founders of English schools and colleges
Knights Bachelor


Pitolisant, sold under the brand name Wakix among others, is a medication for the treatment of excessive daytime sleepiness in adults with narcolepsy. It is a histamine 3 (H3) receptor antagonist/inverse agonist. It represents the first commercially available medication in its class. Pitolisant enhances the activity of histaminergic neurons in the brain that function to improve a person's wakefulness.

The most common side effects include difficulty sleeping, nausea, and feeling worried.

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.

Medical uses
Pitolisant is indicated in adults for the treatment of narcolepsy. Narcolepsy is a chronic sleep disorder that causes overwhelming daytime drowsiness. Pitolisant is also indicated to improve alertness and reduce excessive daytime sleepiness in adults with obstructive sleep apnea.

Side effects
The most common side effects include insomnia, headache, nausea, anxiety, irritability, dizziness, depression, tremor, sleep disorders, tiredness, vomiting, vertigo, and dyspepsia (heartburn). Rare but serious side effects are abnormal loss of weight and spontaneous abortion.

Pharmacology
Pitolisant is an inverse agonist of the histamine 3 (H3) autoreceptor. The H3 autoreceptors regulate histaminergic activity in the central nervous system (and to a lesser extent, the peripheral nervous system) by inhibiting histamine synthesis and release upon binding to endogenous histamine. By preventing the binding of endogenous histamine at the H3, as well as producing a response opposite to that of endogenous histamine at the receptor (inverse agonism), pitolisant enhances histaminergic activity in the brain.

History
Pitolisant is marketed in the European Union by Bioprojet Pharma. It was approved for medical use in the European Union in March 2016.

The FDA approved pitolisant for excessive daytime sleepiness in participants with narcolepsy based primarily on evidence from two trials (Trial 1/NCT01067222, Trial 2/NCT01638403). An additional trial (Trial 3/NCT01800045), in which participants with a different type of narcolepsy were exposed to the same dose of pitolisant, was used to add data for evaluation of side effects. The trials were conducted in Europe and South America.

The two primary trials enrolled adults with narcolepsy and excessive daytime sleepiness. Participants received pitolisant, placebo, or an approved drug for narcolepsy for eight weeks. For participants receiving pitolisant, the dose could be increased during the first three weeks but had to remain the same for the next five weeks. Neither the participants nor the healthcare providers knew which treatment was being given during the trial.

The benefit of pitolisant was evaluated by comparing changes in daytime sleepiness during the trial between pitolisant- and placebo-treated participants. To measure the daytime sleepiness, the investigators used a scale called the Epworth Sleepiness Scale (ESS). The ESS asks participants to rate the likelihood that they would fall asleep while doing eight daily activities (such as sitting and reading or watching television). Participants rate each item from zero (would never doze) to three (high chance of dozing).

Pitolisant was approved by the U.S. Food and Drug Administration (FDA) in August 2019. It was granted orphan drug designation for the treatment of narcolepsy, fast track designation for the treatment of excessive daytime sleepiness  and cataplexy in people with narcolepsy, and breakthrough therapy designation for the treatment of cataplexy in people with narcolepsy.

References

External links

Chloroarenes
CYP2D6 inhibitors
Ethers
H3 receptor antagonists
1-Piperidinyl compounds
Stimulants
Orphan drugs


Country Store is a variety of muesli manufactured by Kellogg's. It is high in fibre and available only in the European Union. It is not sold in the United States due to its higher production cost compared to processed artificial cereals such as Froot Loops and Apple Jacks (using artificial flavours and colours would increase profits for Kellogg's but is illegal in Europe so the company only sells natural cereals there). Country Store was introduced into the United Kingdom and Ireland around 1974 with a TV advert voiced by Michael Jayston.

Ingredients
Country Store contains a number of natural ingredients, including sugar, brown sugar, glucose-fructose syrup, salt, milk whey powder, oats, maize, wholewheat, sultanas, wheat bran, hazelnuts, dried apple and barley malt flavouring.

External links

Kellogg's cereals
British brands
Irish brands


Riad Jarjour is a Syrian Christian clergyman who has served as General Secretary of the Middle East Council of Churches between 1994 and 2003. Born in Aleppo and grew up in the city of Homs.

Biography
While in high school, he spent one year in Green Bay, Wisconsin, as an exchange student. He completed his B.A. degree at Hagazian College and M.Div. at the Near East School of Theology, both in Beirut, Lebanon, and in 1978 was ordained a Minister in the Evangelical Synod of Syria and Lebanon.

Further studies include the STM degree in Islamic studies from the Near East School of Theology, and the D.Min. degree at McCormick Theological Seminary, Chicago, Ill. A chaplain in South Lebanon for several years, he joined the Middle East Council of Churches in 1978 as Director of the Youth Program, and in 1983 became co-director, with his wife, Roseangela, of the Ayia Napa Conference Center in Ayia Napa, Cyprus.

In 1985 he was named Associate General Secretary of the MECC and Director of its Unit on Education and Renewal. The MECC has become increasingly involved in Christian-Muslim dialogue under the Rev. Jarjour's leadership.

Jarjour presently is the general secretary of the Arab Group For Muslim-Christian Dialogue.

Legacy
During his nine-year tenure with the MECC, Jarjour has brought the council's program closer to the grass roots of the churches, rationalized its structure. He managed to maintain the council's effective ministries despite the shrinking financial resources. He also worked to strengthen the ministry of the council among its member churches and especially in the Holy land. He supported the cause of the Palestinian people, and advocated for the preservation of the Arab identity of Jerusalem.

He has organized and led several events like the Muslim-Christian conference on Jerusalem (Beirut, June 14–17, 1996) and several other substantial events over the following years. Over the years, the council's role as the venue for communication between middle eastern Christians and Muslims was greatly enhanced. Rev. Jarjour was among the key contributors to and editors of the landmark document of the Arab Working Group for Christian Muslim Dialogue, “Dialogue and Coexistence: An Arab Muslim-Christian Covenant” (finalized in Cairo in December 2001).

Jarjour was instrumental in planning and administering an important meeting between the heads of the Middle East's churches (The Council of Nicosia). Under his administration the council's relief work in Iraq continued to be effective and timely. The council was also on the ground to respond to the earthquakes in Iran and Turkey. He administered the program on Justice, Peace and Human Rights which evolved into an effective instrument for analysis, training and promoting vital concerns not only of Christians but of all groups in middle eastern society.

Jarjour's led the Arab Group for Christian Muslim Dialogue on activities in the region and internationally, which culminated in an important document on Christian Muslim dialogue (The Christian Muslim covenant). He also developed the activities of the world association for Christian communication in the Middle East.

He is also a frequent speaker in international circles, on the ecclesiastical, religious, social and historical situation of the Middle East region.

External links
 Arab Group For Muslim-Christian Dialogue

Syrian Christians
People from Homs
Living people
Year of birth missing (living people)


William Horton (17 February 1905 – 19 January 1992) was an English professional rugby league footballer who played in the 1920s and 1930s. He played at representative level for Great Britain, England and Yorkshire, and at club level for Wakefield Trinity (Heritage № 307) (captain), as a , or , i.e. number 11 or 12, or 13, during the era of contested scrums.

Background
Bill Horton was born in Knottingley, Wakefield, West Riding of Yorkshire, England, and he died aged 86.

Playing career

International honours
Bill Horton won caps for England while at Wakefield Trinity in 1928 against Wales, in 1929 against Other Nationalities, in 1932 against Wales, in 1933 against Australia, in 1936 against Wales, and won caps for Great Britain while at Wakefield Trinity in 1928 against Australia (3 matches), New Zealand (3 matches), in 1929-30 against Australia, in 1932 against Australia (3 matches), New Zealand, and in 1933 against Australia (3 matches).

County honours
Bill Horton won cap(s) for Yorkshire while at Wakefield Trinity.

County Cup Final appearances
Bill Horton played right-, i.e. number 12, in Wakefield Trinity's 9-8 victory over Batley in the 1924–25 Yorkshire County Cup Final during the 1924–25 season at Headingley Rugby Stadium, Leeds on Saturday 22 November 1924, played right- in the 3-10 defeat by Huddersfield in the 1926–27 Yorkshire County Cup Final during the 1926–27 season at Headingley Rugby Stadium, Leeds on Wednesday 1 December 1926, played left-, i.e. number 11, in the 0-8 defeat by Leeds in the 1932–33 Yorkshire County Cup Final during the 1932–33 season at Fartown Ground, Huddersfield on Saturday 19 November 1932, played left- in the 5-5 draw with Leeds in the 1934–35 Yorkshire County Cup Final during the 1934–35 season at Crown Flatt, Dewsbury on Saturday 27 October 1934, played left- in the 2-2 draw with Leeds in the 1934–35 Yorkshire County Cup Final replay during the 1934–35 season at Fartown Ground, Huddersfield on Wednesday 31 October 1934, played left- in the 0-13 defeat by Leeds in the 1934–35 Yorkshire County Cup Final second replay during the 1934–35 season at Parkside, Hunslet on Wednesday 7 November 1934, and played left- in the 2-9 defeat by York in the 1936–37 Yorkshire County Cup Final during the 1936–37 season at Headingley Rugby Stadium, Leeds on Saturday 17 October 1936.

Notable tour matches
Bill Horton played left-, i.e. number 11, in Wakefield Trinity's 6-17 defeat by Australia in the 1933–34 Kangaroo tour of Great Britain match during the 1933–34 season at Belle Vue, Wakefield on Saturday 28 October 1933.

Club career
Bill Horton made his début for Wakefield Trinity during August 1924, he played his last match for Wakefield Trinity during the 1937–38 season, and he appears to have scored no drop-goals (or field-goals as they are currently known in Australasia), but prior to the 1974–75 season all goals, whether; conversions, penalties, or drop-goals, scored 2-points, consequently prior to this date drop-goals were often not explicitly documented, therefore '0' drop-goals may indicate drop-goals not recorded, rather than no drop-goals scored. In addition, prior to the 1949–50 season, the archaic field-goal was also still a valid means of scoring points.

Genealogical information
Bill Horton married Sybil Irene (née Webber) (birth registered during second ¼ 1903 in Bristol district – death unknown) during June 1927 in Wakefield. They had children; John A. Horton (birth registered during first ¼ 1928 in Wakefield district).

References

Lindley, John (1960). Dreadnoughts - A HISTORY OF Wakefield Trinity F. C. 1873 - 1960. John Lindley Son & Co Ltd. ISBN n/a

External links
Knottingley In 1968 - 25 July 1968 - Aire Street History
RootsWeb > Archiver > WEST-RIDING > 1999-03 > 0920940220
RootsWeb > Archiver > WEST-RIDING > 1999-03 > 0922827299
RootsWeb > Archiver > KILBURN-UK > 2002-01 > 1010751181
(archived by web.archive.org) Green & Gold makes its début

1905 births
1992 deaths
England national rugby league team players
English rugby league players
Great Britain national rugby league team players
Place of death missing
Rugby league locks
Rugby league players from Wakefield
Rugby league second-rows
Sportspeople from Knottingley
Wakefield Trinity captains
Wakefield Trinity players
Yorkshire rugby league team players


Prince Paul may refer to:
Prince Paul of Romania
Prince Paul of Thurn and Taxis
Prince Paul of Württemberg
Prince Paul of Yugoslavia
Prince Paul (producer)


Channel M Breakfast is a regional breakfast television programme, produced by the Greater Manchester local television station, Channel M. Launched on Monday 16 April 2007 and broadcast from the headquarters of Channel M at Urbis in Manchester city centre, the programme covered news, sport, features and entertainment from Greater Manchester and was the only regional television programme of its kind in the United Kingdom.

It was broadcast on weekdays between 6am and 9am and was presented by Byron Evans and Nikki Dean. The editor was Vanessa Williams.

The programme was axed on Friday 15 May 2009 as part of severe cutbacks to programming output and staffing levels at the station.

After the programme ended, for a short while, the first two hours (6am to 8am) was used to broadcast live footage of the area's traffic cameras accompanied by a simulcast of Real Radio North West, and when the live footage from the traffic cameras ceased a holding slide was shown during the Real Radio simulcasts.

References

External links
Channel M Breakfast official site

Mass media in Manchester
2007 British television series debuts
2009 British television series endings
Breakfast television in the United Kingdom


Robert de Vere, 19th Earl of Oxford (b. after 23 August 1575 – 7 August 1632) was a British soldier, and the penultimate Earl of Oxford.

Life

Robert was the son of Hugh de Vere (a great-grandson of John de Vere, 15th Earl of Oxford) and Eleanor Walsh. He was the second cousin of Henry de Vere, 18th Earl of Oxford.

When Henry died sometime between 2 and 9 June 1625, Robert emerged as the heir apparent to the earldom. Robert's claim was by his descent from the 15th Earl of Oxford, but his title was not immediately confirmed, although his right to the peerage was acknowledged by the Lord Chief Justice, Sir Ranulph Crewe in his celebrated "Time hath his revolutions" judgment. He was considered to have an inadequate estate in England, and only after a long debate in the House of Lords in April 1626 did he eventually secure his title and right to attend Parliament. He subsequently returned to his home in the Low Countries, where he had made a career for himself as a soldier in the Dutch army.

He married Beatrice, or Bauck, daughter of the Dutch nobleman Sierck van Hemmema. In 1632, Robert was killed while taking part in the siege of Maastricht. His title passed to his five-year-old son Aubrey, who would, in turn, become the last in an almost 600-year line of de Vere earls of Oxford.

References

1575 births
1632 deaths
16th-century English nobility
17th-century English nobility
Robert de Vere, 19th Earl
Robert


Q-D-Š is a triconsonantal Semitic root meaning "sacred, holy", derived from a concept central to ancient Semitic religion. From a basic verbal meaning "to consecrate, to purify", it could  be used as an adjective meaning "holy", or as a  substantive referring to a "sanctuary, sacred object, sacred personnel."

The root is reflected as q-d-š (Phoenician , Hebrew ) in Northwest Semitic and as q-d-s () in Central and South Semitic.
In Akkadian texts, the verb conjugated from this root meant to "clean, purify."

Canaanite religion
It was used this way in Ugaritic, as for example, in the words qidšu (meaning "holy place" or "chapel") and qad(i)šu (meaning "consecrated gift" or "cultic personnel").
In some Ugaritic texts, qdš is used as a divine epithet. For example, the gods are referred to as "the sons of holiness" or "the holy ones" (bn qdš), and in the Ugaritic  Legend of Keret, the hero is described as "the son of El and the offspring of the Benevolent One and qdš ".

William Foxwell Albright believed that Qudšu (meaning "holiness") was a common Canaanite appellation for the goddess Asherah, and Albright's mentee Frank Moore Cross claimed qdš was used as a divine epithet for both Asherah and the Ugaritic goddess, Athirat.
Johanna Stucky claims she may have been a deity in her own right.

Depictions of a goddess in inscriptions from Dynastic Egypt, thought to be Canaanite since she is referred to as Qdš (often transliterated in English as Qedesha, Qudshu or Qetesh), show a woman in the nude, with curly hair and raised arms carrying lilies and serpents. Qdš is also depicted in the pantheon of gods at Memphis, Egypt possibly indicating worship of her as independent deity there. The word qdš also appears in the Pyrgi Tablets, a Phoenician text found in Italy that dates back to 500 BCE.

Hebrew
Qudšu was later used in Jewish Aramaic to refer to God.

Words derived from the root qdš appear some 830 times in the Hebrew Bible.
Its use in the Hebrew Bible evokes ideas of separation from the profane, and proximity to the Otherness of God, while in nonbiblical Semitic texts, recent interpretations of its meaning link it to ideas of consecration, belonging, and purification.

The Hebrew language is called "The Holy Tongue" ( "Lashon HaKodesh") in Judaism.
In addition, the Hebrew term for the Holy Temple in Jerusalem is Beit Hamikdash (, "the holy house"), and Ir Ha-Kodesh (, "City of the Holy"), the latter being one of the tens of Hebrew names for Jerusalem.

Three theological terms that come from this root are Kiddush, which is sanctification of the Sabbath or a festival with a blessing over wine before the evening and noon meals, Kaddish, which is the sanctification prayer, and mourner's prayer, and Kedushah which is the responsive section of the reader's repetition of the Amidah.

Qedeshah () is a word derived from the Q-D-Š root, which is used in the Hebrew Bible to describe a particular sort of woman. Historically this has been understood to be a sacred prostitute in a temple fertility cult. However modern scholarship has revealed that the evidence for this is extremely tenuous. Modern scholars have provided significant criticism of the common belief that any culture in the Mediterranean and Ancient Near East ever practised sacred prostitution.  Mayer Gruber (1986) suggested the word's usage reflected a more primitive base-meaning in the Q-D-Š root of "set apart", hence "she who is set apart for sexual services, a prostitute".  But this interpretation of the root has not generally been taken up.  The question of how a word with a root meaning of "consecrated one" evidently came to be associated with common prostitution continues to be a topic of ongoing discussion.

Two different words describing places in the Hebrew Bible use this root. One is Kedesh, which refers to a Canaanite village first documented in Joshua 20:7 and later in 2 Kings 15:29. The other is Kadesh, a place in the south of Ancient Israel, mentioned in  and .

Arabic
The verb form of Q-D-S in Arabic (qadus) means "to be holy" or "to be pure, immaculate". Quds can be used as a noun to denote "paradise" or as an adjective meaning "purity" or "holiness". The definite noun form, al-Quds (, "the holy one"), is the most common of seventeen Arabic Names of Jerusalem and derives from the Aramaean word for "temple" (qōdšā). The Turkish word for Jerusalem, , derives from the Arabic name.
Two other names for Jerusalem also derive from the Q-D-S root: Bayt al-Muqqadas ("the holy house") and Bayt al-Maqdis. The wider area around Jerusalem, or the Holy Land, is referred to in Arabic and in Islamic sources as al ard al-muqaddasa (also Bilād al-Muqaddasa), as it is full of shrines and connections to prophets and saints. The Christian Bible is known in Arabic as al-Kitāb al-Muqaddas. Muqaddas in Arabic means not only "holy" and "sacred", but also "hallowed, sanctified, dedicated, consecrated."

Al-Quds also appears in Arabic as part of a phrase to refer to the Holy Spirit, Rúḥu 'l-Quds (or Rūḥu 'l'Qudus), with Ruh meaning "spirit".
This phrase appears in the Qur'an a number of times, where it is thought to refer in some cases to the angel Gabriel.

The concept of Rúḥu 'l-Quds is also discussed at length by the Sufi mystic, ʻAbd al-Karim al-Jili, who further distinguishes between two other concepts derived from the Q-D-S root in Arabic: qudsi ("holy one") and aqdasi ("most holy one"). The qudsi is one who "unceasingly contemplates the Divine consciousness sirr ['secret'], which is his origin" and is "illuminated" by it, whereas the aqdasi ("most holy one") is one who is actually united with this Essence.

Qudsi is also used in Arabic to refer to a Jerusalemite, or a native/resident of Jerusalem. It and its derivatives, such as Maqdisi and al-Muqaddasi are used in Arabic surnames or as appellatives assigned to those who come from or live in Jerusalem.

The religious terms Hadith Qudsi ("holy hadith") and Tafsir Qudsi ("sacred commentary") also incorporate qudsi, though in this case it is used as an adjective, rather than a noun or pronoun. Tafsir Qudsi is a form of Quranic commentary, while Hadith Qudsi refers to the "utterances of God through the Prophet", thus enjoying a status higher than that the hadith writings in general, though lower than that of the Qur'an.

Other derivatives of Q-D-S in Arabic include qudus, which means "purity", "sanctity", "saint" or "holy", and qadas, which is used to refer to a "small cup or plate", often used to put forth offerings at holy sites. Taqdis means to "purify, sanctify, consecrate to God," taqqadus is to "be purified, sanctified, consecrated," and taqâdus means to "play the saint". Istiqdas means "to deem holy."

Maltese
The root Q-D-S in Maltese is used in a religious sense, and means "holy, sanctified, saintly", its use is very similar to that of Christian Arabs, as the Maltese language uses mostly Arabic terms and even some Muslim terms in religion. Some examples are qaddis (holy, saint), tqaddis (sanctification), qdusija (holiness, saintliness), maqdas (temple, place of worship), mqaddes (sacred, hallowed) and quddiesa (mass), amongst many more.

See also

 Al-Quds (disambiguation)
 Battle of Kadesh
 Bris Kodesh
 Kadesh Campaign
 Kadosh
 Kitáb-i-Aqdas
 Kodesh Hakodashim
 Qadas
 Qadesh (disambiguation)
 Sifrei Kodesh

References

Bibliography

Triconsonantal roots
Aramaic words and phrases
Arabic words and phrases
Hebrew words and phrases
Holiness


DJ Cameo is an English DJ and former host of "Pirate Sessions", a now-defunct Sunday afternoon grime show on the digital UK radio station BBC 1Xtra. He later hosted the Tuesday night UKG show, but on 4 November 2015 it was announced that he would be replaced by a new DJ called Jamz Supernova who would be playing R&B. The music Cameo produces varies from 2-step vocals, to 4x4, to grime, and sublow. In 2004, Cameo was voted winner of the "Best Newcomer" Award for the garage scene's 2004 Peoples Choice Awards held in London. Cameo also received two back to back awards on behalf of Uptown Records, winner of best record shop.

Biography
DJ Cameo began his DJing career in 1997 playing in local bars and clubs in West London. His main influences at that time were Tuff Jam, EZ and the Dreem Teem. In March 1999, Cameo landed a set on London's 92.5 Taste FM alongside MCs Mr. Kaos and Double G, together collectively known as The Specialist Crew and later Special Edition. In their weekly 4pm–6pm Sunday show, they were amongst the early pioneers of a changing scene and introduced the concept of 'radio raving' with 2 MCs effectively 'bringing a rave into your living room'. This allowed Cameo to be heard on the UK underground music scene and to gain experience in working on a radio station. With success on Taste FM, Cameo also featured on other pirate stations such as Delight FM, Ice FM and Lush FM.

In 2001, he secured a job at Uptown Records, a European underground music store and has since been promoted to head buyer for the UK garage department. That same year, Cameo teamed up with Danny C and MC Viper to produce "Addicted". Cameo then got involved with producer J-Sweet to produce the underground track "Hi Grade" featuring Mr. Kaos and Double G that was then signed to the MOBO 2002 compilation, and more recently the 2003 garage anthem "Original Bad Girl Style" featuring Gemma Fox for Ministry of Sound's Street Beats compilation.

In October 2005, Cameo started his own label, On A Level, and Kamikaze Recordings working with artists such as Jon E Cash, DaVinChe, Terror Danger, P-Jam, Dexplicit, Vital, Delinquent, TnT, J-Sweet, IMP, Jiggalo, Black Jack and Scandalous. Also in 2005, the Garage Anthems CD compilation, mixed by Cameo was released on Virgin Records. Cameo went on to become head A&R of Def Jam mobile, a ringtone company offering UK and US tracks for download. That same year, Cameo promoted his Hot Off The Block Grime Allstars concert tour alongside Rebecka Prochnik. It showcased established and new UKG talent in a live concert format enabling fans around the world to truly experience the UKG phenomena on their doorstep. A world tour was set up with dates in New York, Germany, Spain, Sweden and Paris. The UK was also covered with dates at Glastonbury Festival, V Festival, Cargo and various universities. The tour included acts such as Crazy Titch & J2K, Lethal B, Roll Deep, JME, Skepta, Bruza, No Lay, L Man, Purple and Tinchy Stryder, to name a few. It aimed to take the UKG scene to another level providing artists and producers with unlimited global exposure.

In early 2006, on behalf of 1xtra and BBC Radio 3, Cameo hosted Urban Classic, a music event which brought urban street stars such as Bruza Purple Pace Tor, Faith Sfx and Davinche together with the BBC Symphony Orchestra for a performance at the Hackney Empire. Cameo also appeared on the TV drama series Dubplate Drama.

Discography
Garage Anthems 2005
The Sound of the Pirates
DJ Cameo Presents Bassline
Black Heart EP (2015)

References

External links
DJ Cameo playing on Taste FM on YouTube
Taste FM 92.5 on YouTube
Interview With Underground Kulture

Year of birth missing (living people)
Living people
Black British radio presenters
Grime music artists
UK garage musicians
BBC Radio 1Xtra presenters
English people of Saint Lucian descent
Electronic dance music DJs


Treasure Coast Square is a shopping mall in Martin County, Florida, United States. It comprises 115 stores, including anchor stores Dillard's, JCPenney, and Macy's, as well as a food court and Regal 16-screen movie theater. The mall is managed by Simon Property Group, and opened in 1987.

History
Developed by Edward J. DeBartolo, the mall opened in 1987 with original anchor tenants J. C. Penney, Jordan Marsh, and Lord & Taylor. The mall's opening caused the decline of the existing Martin Square Mall in nearby Stuart, from which J. C. Penney relocated, and Boca Mall (now known as Mizner Park) in Boca Raton.

The opening of the mall attracted nearly 800,000 square feet of new retail development in its area in the first ten years of opening.

References

External links
 Treasure Coast Square Mall home page

Simon Property Group
Shopping malls in Florida
Buildings and structures in Martin County, Florida
Tourist attractions in Martin County, Florida
Shopping malls established in 1987


Gabaculine is a naturally occurring neurotoxin first isolated from the bacteria Streptomyces toyacaensis, which acts as a potent and irreversible GABA transaminase inhibitor, and also a GABA reuptake inhibitor. Gabaculine is also known as 3-amino-2,3-dihydrobenzoic acid hydrochloride  and 5-amino cyclohexa-1,3 dienyl carboxylic acid. Gabaculine increased GABA levels in the brain and had an effect on  convulsivity in mice.

Mechanism of action
Gabaculine includes a comparable structure to GABA and a dihydrobenzene ring. This comparable GABA structure is used in order to be able to take the place of GABA during the first steps of transamination, including transaldimination and 1,3-prototrophic shift to the pyridoxamine imine. Following this, a proton from the dihydrobenzene ring is abstracted by an enzymatic base, thus causing the ring to become aromatic. The aromatic stabilization energy of the aromatic ring is what causes this reaction to be irreversible, thus causing the complex not to react further.

Preclinical studies
Animal studies to determine the effect of gabaculine on GABA levels in the brain were heavily conducted around the 1970s. These in vivo studies involved mostly the use of mice that underwent intravenous administration of this drug. Each of these studies concluded that gabaculine has a great potential to increase the GABA levels in the brain of these mice in a time dependent manner.
Along with determining the effect of GABA levels, in vivo studies were conducted to investigate the ability of gabaculine to inhibit convulsions in mice. Results indicated that gabaculine provided a clear anticonvulsant effect against seizures induced by high doses of chemoconvulsants or electroshock.
The toxicity of this compound was also investigated using animal mouse models. This study showed that at anticonvulsant doses, gabaculine is extremely potent and toxic when compared to other GABA transaminase inhibitors, with an ED50 of 35 mg/kg and  of 86 mg/kg. Because of this potential lethal effect, gabaculine was proved to be too toxic for use as a drug however, it can still be used as a compound to alter GABA levels in studies of experimental epilepsy.

Regulation
Gabaculine has not been approved by the FDA as a pharmaceutical entity; however, it can be used as a chemical compound for research purposes only. This compound is not considered a hazardous substance according to OSHA 29 CFR 1910.1200.

References

Amino acids
Gamma-Amino acids
Neurotoxins
GABA transaminase inhibitors
GABA reuptake inhibitors
GABA analogues


Ancient Spirit Rising is the fifth album by Domine. It was recorded in January 2007 and released under Japanese label Avalon in February 2007.

Track listing
All tracks by Enrico Paoli except where noted.

 "The Messenger" – 6:24
 "Tempest Calling" – 5:59
 "The Lady of Shalott" – 9:14
 "Stand Alone (After the Fall)" – 4:28
 "Ancient Spirit Rising" – 9:22
 "On the Wings of the Firebird" – 6:32
 "Another Time, Another Place, Another Space" (Riccardo Iacono, Paoli) – 7:10
 "Sky Rider" – 4:56
 "How the Mighty Have Fallen" – 7:42

Personnel
 Morby – vocals
 Enrico Paoli – guitars
 Riccardo Paoli – bass
 Riccardo Iacono – keyboards
 Stefano Bonini – drums

References

External links

2007 albums
Domine albums


David Hall was an Irish Labour Party politician. He was elected to Dáil Éireann as a Labour Teachta Dála (TD) for the Meath constituency at the 1923 general election, and was re-elected at the June 1927 general election. He did not contest the September 1927 general election.

References

Year of birth missing
Year of death missing
Labour Party (Ireland) TDs
Members of the 4th Dáil
Members of the 5th Dáil
Politicians from County Meath


Ian James Brooks (21 April 1928 – 20 April 2022) was a New Zealand politician of the Labour Party.

Early life and career
Brooks was born in Blenheim on 21 April 1928, the son of Ernest Brooks, and was educated at Marlborough College. He worked in the grocery trade for eight years and was then a senior clerk at the New Zealand Post Office for twenty years. He was a part-time farmer, and his 1940s Allis-Chalmers model C tractor is on display at Marlborough Museum.

In 1954, he married Lowis Rita Terrill, the daughter of Leonard Terrill. They had two sons and two daughters.

Political career

Brooks unsuccessfully contested the  electorate in the , but he was beaten by the incumbent, Tom Shand of the National Party. After Shand's death only days after the general election, Brooks had a decisive win against Shand's son in the resulting by-election in February  turning a 2500 vote loss from three months earlier into an 1100 vote winning margin. The Police once urged him to cancel an electorate meeting in Hanmer Springs as they had received a death threat against him over his opposition to the Vietnam War. He held the Marlborough electorate until he was defeated in  by National's Ed Latter for what was usually a safe National seat.

He stood once more in the Marlborough electorate in the  but was narrowly defeated by National's Doug Kidd.

Life after politics
In his spare time, Brooks grew bulbs. His parents were in The Salvation Army and Brooks joined them as a child, and remained an active member in Blenheim, playing the bass saxhorn in the Salvation Army band. Brooks was widowed by the death of his wife, Lowis, in 2016. He died on 20 April 2022 at Wairau Hospital in Blenheim, the day before his 94th birthday.

References

External links
Wedding photo hosted by Marlborough Museum

1928 births
2022 deaths
New Zealand Labour Party MPs
Unsuccessful candidates in the 1975 New Zealand general election
Unsuccessful candidates in the 1969 New Zealand general election
Members of the New Zealand House of Representatives
New Zealand MPs for South Island electorates
People educated at Marlborough Boys' College


Nipecotic acid is a GABA uptake inhibitor used in scientific research.

See also
 Deramciclane
 Tiagabine
  Niacin

References

3-Piperidinyl compounds
GABA reuptake inhibitors
Glycine receptor antagonists


Alberto Frison (born 22 January 1988) is an Italian footballer.

Club career

Treviso
Born in Mirano, Veneto. Frison started his professional career at Veneto side Treviso. He played for Treviso's youth set-up from 2000 to 2007 and was part of the Primavera under-20 team since the 2005–06 season. Frison was primary deployed as the first choice goalkeeper for the Primavera squad, before being promoted to the first team in 2006. He was awarded the number 12 jersey in the first team, and worked as the fourth choice goalkeeper behind Vlada Avramov, Alex Cordaz and Maxminio Montresor. Frison officially graduated from the youth team in June 2007, and was loaned to Lega Pro Prima Divisione side Manfredonia in July 2007. With the Lega Pro Prima Divisione club, Frison was the first choice goalkeeper, ahead of Giacomo Bindi and Manolo Leacche. His performances at the club were not enough to avoid relegation as Manfredonia finished last in Group A and were relegated to the Lega Pro Seconda Divisione as a result.

On 30 June 2008, Frison returned to Treviso, and ahead of the 2008–09 Serie B season, the goalkeeper was retained to the first team, to act as an understudy to Cordaz. On 1 September, however, Frison transferred to fellow Serie B side Vicenza in a co-ownership deal, for €300,000, and in exchange, veteran Matteo Guardalben moved from Vicenza to Treviso as part of the deal, for €50,000.

Vicenza
Frison officially joined Vicenza on the deadline day of the 2008 summer transfer window. At Vicenza, he was awarded the number 1 jersey, and he worked as understudy to veteran goalkeeper, Marco Fortin, but Frison went on to make 8 league appearances that season. In June 2009 Vicenza bought Frison outright from Treviso for an additional €5,000. Treviso went bankrupted in summer 2009.

During the 2009–10 Serie B campaign, Frison continued as the club's second choice goalkeeper behind Fortin and ahead of Cristian Cicioni and José Rocchi. On 18 January 2010, Serie A side Genoa signed Frison on a six-month loan deal from Vicenza. In return, Danilo Russo moved to Vicenza in a co-ownership agreement. Once at Genoa, Frison was given the number 1 jersey, and served as the third choice goalkeeper behind Marco Amelia and Alessio Scarpi. Despite making no Serie A appearances for the Ligurian club, Frison played a friendly match for Genoa at the end of season.

Frison returned to Vicenza on 30 June 2010, ahead of the 2010–11 Serie B season. Upon his return to the club, Frison became a regular at the biancorossi, making 12 league starts for the club in this first half of the new season. On 19 January 2011, however, he was loaned out to Frosinone. On 31 January 2011, Pierluigi Frattali transferred from Frosinone to Vicenza, in exchange. During his loan spell with Frosinone, Frison became the first choice keeper, making 17 league appearances. On 30 June 2011, Frison returned to Vicenza following the expiration of the loan deal.

Following his return to Vicenza, Frison took the number 88 jersey, and was expected to compete with veteran Paolo Acerbis for a starting spot. He instantly became the club's starting goalkeeper following his return and would go on to become an indispensable part of the team's 2011–12 squad, making over 45 appearances in all competitions with 41 appearances in the league. In January 2012, Frison was strongly linked with a move to several clubs. Frison remained at Vicenza, but was unable to prevent the club's eventual relegation to the Lega Pro Prima Divisione following the play-off loss on aggregate to Empoli.

Catania
On 6 July 2012, Frison transferred to Catania in a co-ownership agreement on a five-year contract. The total cost of the transfer was €650,000, though fullback Raffaele Imparato transferred to Vicenza as part-exchange for free. Frison was expected to compete with Argentina international Mariano Andújar for a starting role following the loan return of Juan Pablo Carrizo to Lazio, the departure of Tomáš Košický to Novara and the expiration of Andrea Campagnolo's contract. Since his arrival at the Sicilian club, Frison has served as a backup to Andújar, and has made three appearances in the 2012–13 Coppa Italia. He would go on to make his Serie A debut, in an away loss to Milan on 28 April 2013, after Andújar was handed a three-match suspension from league play. On 5 May 2013, Frison earned his first Serie A clean sheet in a 3–0 home victory over Siena. In June 2013, Catania signed Frison outright for another €700,000.

Frison became a first choice since mid of 2013–14 Serie A season. He followed the club relegated to 2014–15 Serie B.

In January 2015 Frison was signed by Serie A club U.C. Sampdoria in a temporary deal.

Due to a match-fixing scandal, Catania was relegated to Lega Pro at the start of 2015–16 season. On 31 August 2015, Serie B newcomer Salernitana signed Frison on loan with an obligation to sign outright at the end of season, as well as Moses Odjer in a temporary deal with an option to sign outright. At the same time Cataina signed keeper Luca Liverani (in a 1-year contract), forwards Andrea Russotto and Caetano Calil in definitive deals. However, on 2 September he was released.

Sambenedettese
On 4 August 2016 Frison was signed by Sambenedettese in a 1-year contract.

International career
Frison has been capped for Italy national youth teams since 2004, all in friendly matches. He was named in the 23-man preliminary squad for the 2005 UEFA European Under-17 Football Championship, which Italy automatic qualified as host, but was excluded from the 18-men final squad. After Enrico Alfonso was sent off in the group stage of the tournament, Frison was originally eligible for selection to the squad as emergency backup, but was injured. Frison played his only match for the under-18 team in 2005, ahead of Enrico Alfonso and Paolo Tornaghi.

He was capped for the Italy under-20 team at the 2007–08 Four Nations Tournament, and in an unofficial friendly against Serie D Best XI. Since 2008–09 season, he was called–up to the U21 Serie B representative team. He played in internal friendlies, which the team split into blue and white teams and against each other.

On 1 October 2010, Frison received a call-up from the under-21 team for the first time. He participated in both legs of the 2011 UEFA European Under-21 Football Championship play-off round as an unused substitute. Italy were eliminated and Frison would no longer be eligible to the U21 team of 2011–13 season, effectively ending his short U21 career.

Personal life
He is the son of former football goalkeeper Lorenzo Frison, who played professionally for teams such as Palermo and Pescara in the 1970s and the 1980s.

References

External links

Profile at Football.it
Profile at La Gazetta dello Sport (2009–10)
FIGC National Team data

1988 births
Living people
People from Mirano
Italian men's footballers
Italy men's youth international footballers
Men's association football goalkeepers
Treviso FBC 1993 players
Manfredonia Calcio players
LR Vicenza players
Genoa CFC players
Frosinone Calcio players
Catania FC players
UC Sampdoria players
Serie B players
Footballers from the Metropolitan City of Venice


was a Japanese football player and manager. He played for Japan national team. He also managed Japan's national team.

Biography
Okano coached the Japan national team from 1961 to 1971, becoming the manager for the 1970-1971 season. From 1998 to 2002 he served as the president of the Japan Football Association. Okano was a member of the International Olympic Committee (IOC) from 1990 to 2012, becoming an honorary member in 2012.

Playing career
Okano was born in Taito, Tokyo on August 28, 1931. His parents ran a well-established confectionery shop in Tokyo’s Ueno district. During the war his family escaped from the American air raids to Gunma Prefecture, but Okano stayed to attend a high school. In April 1949 he enrolled to the University of Tokyo and joined a football club there. In 1953 his team won the first national university championships. In 1955, he was selected Japan national team. He played 2 games for Japan in 1955.

Coaching career

In March 1957, Okano graduated in psychology from the Faculty of Letters, and in early 1961 spent three months in West Germany to train as a football coach. Upon return he was appointed as a Japan national team coach under manager Ken Naganuma, he also served as an interpreter for German coach Dettmar Cramer. In 1968 Summer Olympics, Japan won the bronze medals. In 2018, this team was selected Japan Football Hall of Fame. In 1970, he was promoted to the manager as successor Naganuma. He managed at 1970 Asian Games. However, at 1972 Summer Olympics qualification in 1971, following Japan's failure to qualify for 1972 Summer Olympics, Okano resigned.

In October 1974 he joined the Japan Football Association (JFA). Soon after that he became executive director of the Japanese Olympic Committee (JOC); in 1977 he was appointed as its general secretary and in 1989 as its executive director. In September 1990 he became a member of the IOC, and in 1995 of the FIFA Olympic Tournaments' Organizing Committee. He also served as 9th president of JFA (1998-2002) and 1st president of East Asian Football Federation (2004-2006).

In 2005, Okano was selected Japan Football Hall of Fame. Okano died from lung cancer on 2 February 2017 at a Tokyo hospital. He was 85.

National team statistics

Honour
 Blue Ribbon Medal of Honour (1990)
 IOC Silver Pin (1998)
 Blue Dragon Award (South Korea) (2003)
 The Order of the Rising Sun, Gold Rays with Neck Ribbon (2004)
 Japan Football Hall of Fame (2005)
 Honorary member of the International Olympic Committee (2012 - 2017)

References

External links

 Japan National Football Team Database
Japan Football Hall of Fame at Japan Football Association
Japan Football Hall of Fame (Japan team at 1968 Olympics) at Japan Football Association

1931 births
2017 deaths
University of Tokyo alumni
Association football people from Tokyo
Japanese men's footballers
Japan men's international footballers
Japanese football managers
Japan national football team managers
Japanese International Olympic Committee members
People from Taitō
Recipients of the Order of the Rising Sun, 3rd class
Men's association football forwards
Deaths from lung cancer


Phaclofen, or phosphonobaclofen, is a selective antagonist for the GABAB receptor. It was the first selective GABAB antagonist discovered, but its utility was limited by the fact that it does not cross the blood brain barrier.

References

GABAB receptor antagonists
Phosphonic acids
Chlorobenzenes


was a Japanese football player and manager. He managed Japan national team.

Playing career
Takahashi was born in Fukushima on April 11, 1916. He played for Waseda University. He won 1938 Emperor's Cup with Sei Fuwa, Sekiji Sasano, Kunitaka Sueoka, Shogo Kamo and so on. After graduation from university, he played for Hitachi from 1941 to 1958.

Coaching career
From 1955, Takahashi started managering career too. In 1957, he became manager for Japan national team as Shigemaru Takenokoshi successor for tour for China. In 1959, he became manager for Japan U-20 national team for 1959 AFC Youth Championship and won 3rd place. In 1960, he managed for Japan national team as Takenokoshi successor again. He managed at 1962 World Cup qualification and 1962 Asian Games until 1962. After that, he managed for Hitachi.

On February 5, 2000, Takahashi died of pneumonia in Meguro, Tokyo at the age of 83. In 2009, he was selected Japan Football Hall of Fame.

References

External links
Japan Football Hall of Fame at Japan Football Association
Japan Soccer Archive: Biography and pictures

1916 births
2000 deaths
Waseda University alumni
Association football people from Fukushima Prefecture
Japanese men's footballers
Kashiwa Reysol players
Japanese football managers
Japan national football team managers
Men's association football forwards