Television Infrared Observation Satellite

TIROS, or Television Infrared Observation Satellite, is a series of early weather satellites launched by the United States, beginning with TIROS-1 in 1960.  TIROS was the first satellite that was capable of remote sensing of the Earth, enabling scientists to view the Earth from a new perspective: space.  The program, promoted by Harry Wexler, proved the usefulness of satellite weather observation, at a time when military reconnaissance satellites were secretly in development or use.  TIROS demonstrated at that time that "the key to genius is often simplicity." TIROS is an acronym of "Television InfraRed Observation Satellite" and is also the plural of "tiro" which means "a young soldier, a beginner".

Participants in the TIROS project included the National Aeronautics and Space Administration (NASA), United States Army Signal Research and Development Laboratory, Radio Corporation of America, the United States Weather Bureau, the United States Naval Photographic Interpretation Center (NPIC), the Environmental Science Services Administration (ESSA), and the National Oceanic and Atmospheric Administration (NOAA).

Description
The 270 lb (122 kg) satellite was launched into a nearly circular low earth orbit by a Thor Able rocket.  Drum-shaped with a 42-inch (1.1 m) diameter, and height of 19 inches (48 cm), the TIROS satellite carried two six-inch (15 cm) long television cameras. One of the cameras had a wide-angle lens with an f /1.6 aperture that could view an 800-mile-wide area of the Earth.  The other camera had a telephoto lens with an f /1.8 aperture and 10- to 12-power magnification compared to the wide angle camera.

The satellite itself was stabilized in its orbit by spinning like a gyroscope.  When it first separated from the rocket's third stage, it was spinning at about 136 revolutions per minute (rpm).  To take unblurred photographs, a de-spin mechanism slowed the satellite down to 12 rpm after the orbit was accomplished.

The camera shutters made possible the series of still pictures which were stored and transmitted back to earth via 2-watt FM transmitters as the satellite approached one of its ground command points.  After transmission, the tape was erased or cleaned and readied for more recording.

Series

TIROS continued as the more advanced TIROS Operational System (TOS), and eventually was succeeded by the Improved TIROS Operational System (ITOS) or TIROS-M, and then by the TIROS-N and Advanced TIROS-N series of satellites. NOAA-N Prime is the last in the TIROS series of NOAA satellites that observe Earth's weather and the environment.

The naming of the satellites can become confusing because some of them use the same name as the over-seeing organization, such as "ESSA" for TOS satellites overseen by the Environmental Science Services Administration (for example, ESSA-1) and "NOAA" (for example, NOAA-M) for later TIROS-series satellites overseen by the National Oceanic and Atmospheric Administration.

TIROS-1 (A): launched April 1, 1960, suffered electrical system failure on June 15, 1960
TIROS-2 (B): launched November 23, 1960, failed January 22, 1961
TIROS-3 (C): launched July 12, 1961, deactivated February 28, 1962
TIROS-4 (D): launched February 8, 1962, failed on June 30, 1962 (both cameras failed earlier)
TIROS-5 (E): launched June 19, 1962, failed on May 13, 1963
TIROS-6 (F): launched September 18, 1962, failed October 21, 1963
TIROS-7 (G): launched June 19, 1963, deactivated June 3, 1968
TIROS-8 (H): launched December 23, 1963, deactivated July 1, 1967
TIROS-9 (I): launched January 22, 1965, failed February 15, 1967. First Tiros satellite in near-polar orbit
TIROS-10 (OT-1): launched July 2, 1965, deactivated July 1, 1967.

As of June 2009, all TIROS satellites launched between 1960 and 1965 (with the exception of TIROS-7) were still in orbit.

TIROS Operational System
ESSA-1 (OT-3)
ESSA-2 (OT-2)
ESSA-3 (TOS-A)
ESSA-4 (TOS-B)
ESSA-5 (TOS-C)
ESSA-6 (TOS-D)
ESSA-7 (TOS-E)
ESSA-8 (TOS-F)
ESSA-9 (TOS-G)

ITOS/TIROS-M
TIROS-M (ITOS-1): January 23, 1970 launch
NOAA-1 (ITOS-A): December 11, 1970 launch
ITOS-B October 21, 1971 launch; unusable orbit
ITOS-C
NOAA-2 (ITOS-D): October 15, 1972 launch
ITOS-E July 16, 1973 launch, failed to orbit
NOAA-3 (ITOS-F): November 6, 1973 launch
NOAA-4 (ITOS-G): November 15, 1974 launch
NOAA-5 (ITOS-H): July 29, 1976 launch

TIROS-N

TIROS-N (Proto-flight) Launched 13 October 1978 into a 470-nmi orbit; deactivated on 27 February 1981.
NOAA-6 (NOAA-A prior to launch) Launched 27 June 1979 into a 450-nmi orbit. The HIRS, a primary mission sensor, failed 19 September 1983. The satellite exceeded its two-year designed lifetime by almost six years when deactivated on 31 March 1987.
NOAA-B Launched 29 May 1980. It failed to achieve a usable orbit because of a booster engine anomaly.
NOAA-7 (C) Launched 23 June 1981 into a 470-nmi orbit; deactivated June 1986.
NOAA-12 (D) Launched 14 May 1991 into a 450-nmi AM orbit, out of sequence (see below). Placed in standby mode on 14 December 1998, when NOAA-15 became operational and deactivated on 10 August 2007, setting an extended lifetime record of over sixteen years.

Advanced TIROS-N
The Advanced TIROS-N (ATN) spacecraft were similar to the NOAA-A through -D satellites, apart from an enlarged Equipment Support Module to allow integration of additional payloads. A change from the TIROS-N through NOAA-D spacecraft was that spare word locations in the low bit rate data system TIROS Information Processor (TIP) was used for special instruments such as the Earth Radiation Budget Satellite (ERBE) and SBUV/2. The search and rescue (SAR) system became independent, utilizing a special frequency for transmission of data to the ground.
NOAA-8 (E) Launched 28 March 1983 into a  orbit, out of sequence (before NOAA-D) to get the first SAR system on a US satellite operational. Deactivated 29 December 1985, following a thermal runaway which destroyed a battery.
NOAA-9 (F) Launched 12 December 1984 into 470 nmi "afternoon" orbit and was the first satellite to carry an SBUV/2 instrument. It was deactivated on 1 August 1993 but was reactivated three weeks later, after the failure of NOAA-13. The SARR transmitter failed on 18 December 1997 and the satellite was permanently deactivated on 13 February 1998.
NOAA-10 (G) Launched 17 September 1986 into a 450 nmi "morning" orbit. Placed in standby mode on 17 September 1991 (when NOAA-12 became operational) and deactivated on 30 August 2001.
NOAA-11 (H) Launched 24 September 1988 into a 470 nmi PM orbit. Placed in standby mode in March 1995 and was reactivated in May 1997 to provide soundings after an HIRS anomaly on NOAA-12. Decommissioned 16 June 2004.
NOAA-13 (I) Launched 9 August 1993 into a 470 nmi PM orbit; two weeks after launch the spacecraft suffered a catastrophic power system anomaly. Attempts to contact or command the spacecraft were unsuccessful.
NOAA-14 (J) Launched 30 December 1994 into a 470 nmi PM orbit and decommissioned 23 May 2007 after more than twelve years of operation.
NOAA-15 (K) Launched 13 May 1998 into a 450 nmi morning orbit and replaced NOAA-12 on 14 December 1998, as the primary AM spacecraft. Now secondary, with MetOp-B as the AM primary.
NOAA-16 (L) Launched 21 September 2000 into a 470-nmi afternoon orbit; replaced NOAA-14 on 19 March 2001, as the primary AM spacecraft. Decommissioned on 9 June 2014 due to major spacecraft anomaly.
NOAA-17 (M) Launched 24 June 2002 into a 450 nmi AM orbit and decommissioned 10 April 2013.
NOAA-18 (N) Launched 20 May 2005 into a 470 nmi afternoon orbit and replaced NOAA-16 as the PM primary spacecraft on 30 August 2005.
NOAA-19 (N Prime) Launched 6 February 2009 into a 470 nmi afternoon orbit and replaced NOAA-18 as the PM primary spacecraft on 2 June 2009.

References

External links

NASA page on TIROS
NASA page on ESSA
NASA page on ITOS and NOAA
NASA page on TIROS-N
NASA Goddard POES Program - POES Home
NOAA Office of Satellite Operations - POES
TIROS-1 50th Anniversary & Resources on Satellite Meteorology
NASA's YouTube video of TIROS-1

Category:1960 in spaceflight
Category:1961 in spaceflight
Category:1962 in spaceflight
Category:1963 in spaceflight
Category:Weather satellites
Category:Weather satellites of the United States


The Turning Point (1983 film)

The Turning Point (also screened with the English name Held for Questioning; ) is a 1983 East German film directed by Frank Beyer and starring Sylvester Groth, Fred Düren and Klaus Piontek. The film is based on the 1977 novel of the same name by Hermann Kant, which was based on Kant's own experience as a prisoner of war in Poland. The film tells the story of a German prisoner of war at the end of World War II who is wrongly accused of being a war criminal. The film was controversial upon release as Polish commentators criticized that the film showed the Polish army wrongly accusing someone of war crimes. Nevertheless, the film was successful and won several awards and was the East German official submission to the 56th Academy Awards for Best Foreign Language Film.

Plot
In October 1945 the 19-year-old German prisoner of war, Mark Niebuhr (Sylvester Groth) arrives together with other prisoners at a train station in Warsaw. A Polish woman waiting for her train at the station believes that he is the SS officer who murdered her daughter during a raid in Lublin. He is removed from the other prisoners and incarcerated in a single prison cell. Again and again he is interrogated by a Polish officer who is asking him to write down his life story and to tell his real name. The young former soldier asserts that he is Mark Niebuhr and maintains his innocence, not knowing why he has been detained and not understanding why he is being questioned.

After four months of solitary confinement he is transferred to a new prison cell he is sharing with Polish criminals. As a German he is subject to their hatred and is regularly harassed. He is also assigned the most dangerous works, having to remove stones from bombed houses in Warsaw. During one of his assignment he saves a child, but breaks his arm. He is transferred to a hospital where he learns that he is charged with murder.

After his hospital stay he is transferred to a new prison, where he has to share a cell with German prisoners of war. The German prisoners maintain strict military order according to their former ranks. They are led by General Eisensteck (Fred Düren) and Major Lundenbroich (Klaus Piontek) who still cling to fascist ideals. Little by little Niebuhr gets to know his fellow prisoners. Although everyone is maintaining his innocence, Niebuhr slowly realizes that they are murderers and war criminals. He begins to distance himself from his fellow prisoners and realizes his guilt as an ordinary German soldier. While his cell mates are one by one executed, the Polish authorities ultimately believe Niebuhr and release him.

Cast
 Sylvester Groth as Mark Niebuhr
 Fred Düren as General Eisensteck
 Matthias Günther as Hauptsturmführer
 Klaus Piontek as Major Lundenbroich
 Alexander van Heteren as Jan Beveren
 Hans-Uwe Bauer as Obergefreiter Fenske
 Horst Hiemer as gas man
 Günter Junghans as Gestapo inspector Rodloff
 Gustaw Lutkiewicz as Szybko
 Krzysztof Chamiec as Chef
 Andrzej Pieczynski as Second Lieutenant
 Roman Wilhelmi as Ohnehals
 Horst Giese as third German POW

Production and distribution
The Turning Point premiered on 20 January 1984 and was widely released in East Germany on the day after. The film was widely praised by the East German press, with Neues Deutschland declaring the film "a testament to the friendship between the People's Republic of Poland and East Germany". The Polish reaction was very negative and the depiction of the Polish army wrongly accusing a German of war crimes was perceived as anti-Polish. Both the Polish actors in the film and Polish representatives boycotted the premiere of the film. The controversy also resulted in a withdrawal of the film from the Berlin International Film Festival, where it was originally planned to be screened and was expected to successfully compete for the awards. Despite the controversy the film became the top-grossing film of 1983 in East Germany and was released in West Germany to mixed reviews in spring 1984.

Awards and honors

Director Frank Beyer, screenwriter Wolfgang Kohlhaase and the main actor Sylvester Groth were awarded the Heinrich-Greif-Preis in 1984. The Heinrich-Greif Preis was an East German award for film and television productions, named after the German actor Heinrich Greif. The Association of Film and Television Employees (Verband der Film- und Fernsehschaffenden) awarded the critics award of the section theory and film critic in the categories Best Film and Best Actor (Sylvester Groth) in 1983. At the East German National Feature Film Festival in Karl-Marx-Stadt in 1984 the film won the Findling Award and awards in the categories Best Director (Frank Beyer), Best Script (Wolfgang Koohlaase), Best Editing (Rita Hiller), Best Production Design (Alfred Hirschmeier) and Best Young Actor (Sylvester Groth).

Internationally, The Turning Point was screened at the 40th Venice International Film Festival in 1983. The film was also chosen as East Germany's official submission to the 56th Academy Awards for Best Foreign Language Film, but did not manage to receive a nomination.

References

Notes

Bibliography

External links

 The Turning Point at filmportal.de/en
 The Turning Point on the DEFA-Stiftung

Category:1983 films
Category:East German films
Category:Films based on German novels
Category:Films directed by Frank Beyer
Category:German-language films
Category:World War II prisoner of war films
Category:Films set in Poland
Category:Films set in 1945
Category:Films set in 1946
Category:Films whose director won the Heinrich Greif Prize
Category:Films whose writer won the Heinrich Greif Prize
Category:Babelsberg Studio films


Uch Tappeh, Kabudarahang

Uch Tappeh (, also Romanized as Ūch Tappeh and Owch Tappeh) is a village in Sardaran Rural District, in the Central District of Kabudarahang County, Hamadan Province, Iran. At the 2006 census, its population was 55, in 12 families.

References

Category:Populated places in Kabudarahang County


Labuda

Labuda is a surname. Notable people with the surname include:

Frank LaBuda, American politician and judge
Jeanne Labuda (born 1947), American politician
Josef Labuda (born 1941), Slovak volleyball player
Gerard Labuda (born 1916), Polish historian
Marián Labuda (1944–2018), Slovak actor
Dušan Labuda, a founder of Slovak metal band Kalijuge


Yolande Harmer

Yolande Harmer (born Yolande Gabbai, ; 1913–1959) was an Israeli intelligence officer who operated in Egypt in 1948. She was recruited due to her connections in elite and royal circles, she has been described  as "Israel's Mata Hari". A town square in Jerusalem, 'Yolande Harmer Square', is named after her.

Biography
Yolande Gabai (later Harmer and Har-Mor) was born in Alexandria, Egypt, to a Turkish-Jewish mother. She was married three times, the first at the age of 17. Her first husband was called Jacques de Botton. She divorced him after a few years of marriage - having had a son with him, Gilbert de Botton.

Espionage career
Harmer was recruited by Moshe Sharett, secretary of the Jewish Agency political department, when he visited Egypt in 1945 or 1946. They met at a cocktail party. At the time Harmer was working as a journalist and accepted in the highest circles of Egypt society.
She was able to gather intelligence in King Farouk's court in Cairo.  She made many other important contacts including senior editors of Al-Ahram, the most widely circulating Egyptian daily newspaper, Tak ed-Din as-Sulh, the chief assistant of Abdul Rahman Hassan Azzam, and Mahmoud Mahlouf, son of the Grand Mufti of Cairo.

When the Swedish envoy to Egypt, Widar Bagge, fell in love with her, she swayed him to sympathize with the Zionist struggle for self-determination and the freedom of the Jewish people. Eli Peleg, a Yishuv emissary in Cairo, reported Harmer's success with Bagge: "Several months ago he was indifferent to our cause, but today he is an enthusiastic Zionist." The assassination of Folke Bernadotte in September 1948, however, made Bagge's enthusiasm to cool again.

Harmer provided the Yishuv with important strategic information, including the texts of resolutions adopted by the Arab League in 1947 and 1948 declaring that they  "will sacrifice all the political and economic interest of the Arab world in order to save Arab Palestine." She also uncovered Arab military plans for the end of the British Mandate for Palestine. including the creation of Kaukji's Salvation Army in late 1947. By penetrating the  US Embassy, she was able to supply information on the number of Tunisian and Algerian troops fighting the Arabs in Palestine.

However, delivering the information she gathered was problematic: She had a radio transmitter, but no-one to operate it for her. She sent the information using mail services via Europe or the United States, but precious time was often lost. During her work in Egypt she often risked not only her own life, but the life of her son.

In July 1948, Harmer was arrested. In August, after falling ill in jail, she was released and deported. She went to Paris where she worked for the Middle East Department of the Israeli Foreign Ministry, becoming a key figure in that department by 1949. During her work in Paris she maintained her Egyptian contacts, continuing to provide Israel with valuable information. In 1950 she worked in Madrid.

Harmer died of cancer in 1959.

References

Category:Egyptian Jews
Category:Israeli spies
Category:1959 deaths
Category:1913 births
Category:People convicted of spying for Israel


Moni Tonga’uiha

Moni Tonga'uiha (born 6 October 1994) is an American professional rugby union player. He currently plays as a flanker or centre for the New Orleans Gold in Major League Rugby (MLR).

Tonga'uiha has been widely praised for a break out performance in week 1 of the 2020 season including being referred to as an upcoming star by his teammate and 50 cap USA veteran Cam Dolan.

References

Category:1994 births
Category:Living people


Moorean viviparous tree snail

Moorean viviparous tree snail can refer to any one of several species of mollusc:

 Partula aurantia
 Partula exigua
 Partula mirabilis
 Partula mooreana
 Partula suturalis
 Partula taeniata
 Partula tohiveana
 Samoana diaphana

References

Category:Animal common name disambiguation pages


Hexathlon

An hexathlon is a combined event competition consisting of six different sports or contests.

Track and field
An hexathlon in athletics is an event which consists of six track and field events. The word "hexathlon" derives from the Greek words hexa, the number 6, and athlos, meaning contest. A hexathlon is not often organized, mostly at youth levels. It was on the program of the Central American and Caribbean Age Group Championships in Athletics until 2007, South American Youth Championships in Athletics until 1998 and the South American Junior Championships in Athletics until 1974.

The word hexathlon is also used for other forms of combined contests, like bridge, gaming, workouts, etc..

References
Brian Mac Sports Coach

Category:Combined track and field events
Category:Multisports

The hexathlon consists of 75m hurdles, long jump, javelin, high jump, shot put and the 800m.


Masamoto Yashiro

is a Japanese businessman who currently serves as Chairman and CEO of Shinsei Bank and as a director of China Construction Bank.

He attended Kyoto University, graduating with a degree in law, and graduate school at the University of Tokyo. He joined Standard Vacuum Oil Company in 1958 and became a director of Esso Petroleum in 1964. He was appointed Japan chairman of Citibank in 1989.

In 1999, he left Citibank to head the Ripplewood-backed effort to acquire the Long-Term Credit Bank of Japan. In 2000, he was appointed Chairman and CEO of the newly acquired and renamed Shinsei Bank. In 2004 he was also appointed as a director of China Construction Bank. He resigned as CEO of Shinsei in 2005 and as chairman in 2006, but returned as Chairman and CEO in 2008.

References

External links

Category:Japanese businesspeople
Category:1929 births
Category:People from Shinagawa
Category:Living people


Sponge Reef Project

The Sponge Reef Project is a binational scientific project between Germany and Canada to study the sponge reefs off British Columbia, Canada, reefs formed by sponges of the Hexactinellid family.

The project was started in 1999, following the discovery of the reefs in 1991; earlier, this reef type was thought to have existed mainly in the Jurassic period.

External links
The Sponge Reef Project
B.C.'s Reefs Among Science's Great Finds | Straight.com

Category:Reefs of the Pacific Ocean
Category:Reefs


ObjectDB

ObjectDB is an object database for Java. It can be used in client-server mode and in embedded (in process) mode.

Unlike other object databases, ObjectDB does not provide its own proprietary API. Accordingly, working with ObjectDB requires using one of the two standard Java APIs: JPA or JDO. Both APIs are built-in in ObjectDB, so an intermediate ORM software is not needed.

Features
ObjectDB is a cross platform software and can be used on various operating systems with Java SE 5 or higher. It can be integrated into Java EE and Spring web applications and deployed on servlet containers (Tomcat, Jetty) as well as on Java EE application servers (GlassFish, JBoss). It was tested on various JVMs, including HotSpot, JRockit and IBM J9.

The maximum database size is 128 TB (131,072 GB). The number of objects in a database is unlimited (except by the database size).

All the persistable types of JPA and JDO are supported by ObjectDB, including user defined entity classes, user defined embeddable classes, standard Java collections, basic data types (primitive values, wrapper values, String, Date, Time, Timestamp) and any other serializable classes.

Every object in the database has a unique ID. ObjectDB supports both traditional object database IDs, as well as RDBMS like primary keys, including composite primary keys and auto value generation and assignment, as part of its support of JPA, which is mainly an API for RDBMS.

Two query languages are supported. The JDO Query Language (JDOQL), which is based on Java syntax, and the JPA Query Language (JPQL), which is based on SQL syntax. JPA 2 criteria queries are also supported.

ObjectDB automatic schema evolution handles most changes to classes transparently, including adding and removing of persistent fields, changing types of persistent fields, and modifying class hierarchy. Renaming persistable classes and persistent fields is also supported.

Tools and utilities
The following tools and utilities are included in the ObjectDB distribution:

 Database Explorer - GUI tool for querying, viewing and editing database content.
 Database Doctor - Diagnoses and repairs possible database problems.
 Replication - Master-Slave replication (clustering) with unlimited number of slave nodes.
 Online Backup - Database backup by a simple query on an EntityManager.
 Class Enhancer - Boosts performance by preparing classes for persistence.
 Transaction Replayer - Recorder and replayer of database transactions.
 BIRT Reports Driver - Adds ObjectDB as a BIRT data source and JPQL / JDOQL queries as data sets.

References

External links

Category:Proprietary software
Category:Object-oriented database management systems
Category:NoSQL
Category:Cross-platform software


Time to Get Alone

"Time to Get Alone" is a song written by Brian Wilson for the American rock band the Beach Boys. It was released on their 1969 album 20/20 and produced by Carl Wilson.  It is a waltz in the style of baroque pop. Brian originally wrote and produced the song for the band Redwood, which would later become known as Three Dog Night.

PopMatters calls the song "a dream, right on down the line from Carl’s feathery lead vocal—and the way it contrasts with the up-and-down crunch of the waltz backdrop—to the sumptuously layered arrangement of the chorus to the immaculate production job to the unadorned coda (which is from the extended version)."

Recording
Brian Wilson originally planned to give the song (along with "Darlin'") to Redwood. The group began recording on October 12, 1967 while in the midst of sessions for the Beach Boys' Wild Honey (1967). Strings and horns overdubs were added on October 14 with drums and percussion on October 15. Danny Hutton recounted:

After one vocal session, Brian exited the booth and called up his astrologer, who told him that he was on a "down cycle". Brian, who had an aversion to Los Angeles smog, fled the studio and returned the next day with an oxygen tank and mask, taking hits from the tank and sprinting in the alley behind the studio.

According to Chuck Negron, due to the commercial failure of Smiley Smile and Brian's waning commitment to his band, "the other Beach Boys wanted Brian's immense songwriting and producing talents used strictly to enhance their own careers". Negron then noted that he would have done the same thing if in the Beach Boys' position.

The song was finished by the Beach Boys around a year later in 1968 on October 2, October 4, and November 21 at Brian Wilson's home studio with the October 4 session being captured on film. Portions of the footage was later used for an "I Can Hear Music" promotional video.

Personnel
Sourced from Craig Slowinski.
 Carl Wilson – vocals
 Al Jardine – vocals
 Brian Wilson – vocals, piano, harpsichord
 Danny Hutton – piano
 Ron Brown – bass
 Ray Pohlman – bass
 Gene Pello – drums, percussion
 Jay Migliori – flute, clarinet

Cover versions

 1993 – Three Dog Night, Celebrate: The Three Dog Night Story, 1965–1975

References

Category:1969 songs
Category:Baroque pop songs
Category:The Beach Boys songs
Category:Songs written by Brian Wilson
Category:Song recordings produced by the Beach Boys


Hell and Silence

Hell and Silence  is the second Extended Play (EP) by American  pop rock music band
Imagine Dragons, released on June 1, 2010. It was recorded at Battle Born Studios. All songs were written by Imagine Dragons and self-produced; the EP was in part mixed by Grammy nominated engineer Mark Needham. Most of the songs on this EP were remastered and included on Night Visions, excluding "All Eyes" and "Emma".

To promote the EP, the band performed five shows at SXSW 2010 including at the BMI Official Showcase.  While at SXSW they were endorsed by Blue Microphones.  They also toured the western United States with Nico Vega and Saint Motel.  They also performed at Bite of Las Vegas Festival 2010, New Noise Music Festival, Neon Reverb Festival, and Fork Fest. The name of the EP comes from a line in "Emma".

In popular culture
"All Eyes" was featured in the Degrassi: The Next Generation episode Drop It Like It's Hot (Part One). "I Don't Mind" was featured in the promo commercials for American Idol season 11 and MTV's World of Jenks.

"Hear Me" was featured in the soundtrack to the feature film Answers to Nothing, MTV's The Real World: Las Vegas, and performed live on PBS' Vegas In Tune.

Track listing
Track listing and credits taken off of the physical CD copy. All songs written and produced by Imagine Dragons (Ben McKee, Daniel Wayne Sermon, Dan Reynolds, Andrew Tolman and Brittany Tolman), except where noted.

Reception
Jason Bracelin, writing in the Las Vegas Review Journal, gave a glowing review of the EP by stating "Dan Reynolds sounds like a dude with a bull's-eye for a heart".  He continues "With its staccato vocal delivery and huge keys, "All Eyes" sounds destined for the airwaves, the same of which could be said of the wistful "Emma," with its dizzy synth lines and coed harmonies, and the climactic "I Don't Mind," which is powered by ricocheting guitars."

References

External links
 Imagine Dragons Official site
 All Eyes original press
 Blue Microphones YouTube Channel
 u/alleyes on reddit.com

Category:2010 EPs
Category:Imagine Dragons EPs


Al-Merreikh Al-Thagher

Al-Merreikh Al-Thagher Sport Club () also known as Merreikh Port Sudan is a football club in Port Sudan, Sudan.

National
Sudan Premier LeagueChampion (0):Runners-up (0):Third Place (1): 2000 12 Place (1):2007Sudan Cup
Champion (0):
Runners-up (0):

Bort Sudan League

Performance in CAF competitionsCAF Cup: 1 appearance
2001 – First Round

External links
Team profile – soccerway.com

Category:Football clubs in Sudan
Category:Red Sea (state)


Haicheng County

Haicheng County was a historic county in South China, dating to the Ming Dynasty. During the late Ming Dynasty, Haicheng was one of China's most important ports, earning the moniker "Little Suzhou-Hangzhou" (小蘇杭), a reference to the historically prominent trading centers of Hangzhou and Suzhou.

History

Haicheng was elevated to county status on 17 January 1567 during the Ming Dynasty, and was the site of Yuegang (Moon Harbor), a major seaport handling the majority of maritime trade with Southeast Asia. Haicheng County was merged with Longxi County in 1960 to form the modern-day Longhai City in Fujian Province. For most of its history, the administrative center of the county was in Shima (石碼).

References

Category:Former counties of China
Category:County-level divisions of Fujian
Category:History of Fujian
Category:1960s disestablishments in China


The Potter and the Clay

The Potter and the Clay is a 1914 American silent short film directed by George Melford.

Plot

Cast
 Douglas Gerrard as Bertram Trent – a Man of Wealth
 Ollie Kirke (Ollie Kirkby) as Elsie Trent, Bertram's Wife
 Cleo Ridgeley (Cleo Ridgely) as Dorothy Trent, the Daughter
 Marin Sais as Rose Masters
 Elsie Maison as Lillian Masters, Rose's Daughter
 Thomas G. Lingham as Gates, a Gambler
 Jane Wolfe

Production
The film was produced by Kalem Company.

Release
The film was distributed by General Film Company, and was released in American cinemas on September 21, 1914.

References

External links

Category:American films
Category:1914 films
Category:American silent short films
Category:1910s drama films
Category:American drama films
Category:American black-and-white films
Category:Films directed by George Melford


John Alexander Valencia

John Alexander Valencia Hinestroza  (born January 4, 1982) is a Colombian retired footballer who played as a defender.

Career
Valencia began his career in the youth ranks of top Colombian side Independiente Medellín and made his first team debut in 2005. During the 2005 season he was also sent on loan to Romanian club Oțelul Galați. After a brief stay in Romania he returned to Colombia signing with Atlético Bucaramanga. His play with Bucaramanga helped him receive interest from Atlético Junior who than signed Valencia for the 2007 season. Since signing, Valencia established himself as a starter for the Barranquilla club. Valencia helped the club in capturing Categoría Primera A championships in 2010 and 2011.

On January 24, 2012, Valencia signed with Major League Soccer side Chivas USA. His 2013 contract option was declined by the club on February 14, 2013.

Titles

References

External links
Profile at BDFA

Category:1982 births
Category:Living people
Category:Footballers from Medellín
Category:Colombian footballers
Category:Independiente Medellín footballers
Category:ASC Oțelul Galați players
Category:Atlético Bucaramanga footballers
Category:Atlético Junior footballers
Category:Chivas USA players
Category:Deportes Tolima footballers
Category:Rionegro Águilas footballers
Category:Categoría Primera A players
Category:Major League Soccer players
Category:Colombian expatriate footballers
Category:Expatriate footballers in Romania
Category:Expatriate soccer players in the United States
Category:Association football defenders


Izabelin, Lublin Voivodeship

Izabelin  is a village in the administrative district of Gmina Sosnowica, within Parczew County, Lublin Voivodeship, in eastern Poland. It lies approximately  south-east of Parczew and  north-east of the regional capital Lublin.

References

Izabelin


East Canyon State Park

East Canyon State Park is a state park of Utah, USA, featuring a  reservoir.  The park is located northeast of Salt Lake City in Morgan County, Utah.

Park facilities
Located in a narrow-walled canyon, East Canyon State Park is at an elevation of . Park facilities are open year-round, and include a concrete boat launching ramp, paved parking, restrooms, showers, a fish cleaning station, a 33 unit RV campground with full and partial hookups, two covered group-use pavilions, boat rental, and a snack bar.

East Canyon Dam
The East Canyon Dam  is a ,  arch concrete dam. Its base is  wide, and its crest is  wide. The reservoir is fed by East Canyon Creek, and is part of the Weber Basin Project. It was constructed between 1964 and 1966.

References

External links
 East Canyon State Park

Category:Protected areas established in 1962
Category:Protected areas of Morgan County, Utah
Category:State parks of Utah


Discovery and development of tubulin inhibitors

Tubulin inhibitors are chemotherapy drugs that interfere directly with the tubulin system, which is in contrast to those chemotherapy drugs acting on DNA. Microtubules play an important role in eukaryotic cells. Alpha- and beta-tubulin, the main components of microtubules, have gained considerable interest because of their function and biophysical properties and has become the subject of intense study. The addition of tubulin ligands can affect microtubule stability and function, including mitosis, cell motion and intracellular organelle transport. Tubulin binding molecules have generated significant interest after the introduction of the taxanes into clinical oncology and the general use of the vinca alkaloids.  These compounds inhibit cell mitosis by binding to the protein tubulin in the mitotic spindle and preventing polymerization or depolymerization into the microtubules. This mode of action is also shared with another natural agent called colchicine.

History
The first known compound which binds to tubulin was colchicine, it was isolated from the autumn crocus, Colchicum autumnale, but it has not been used for cancer treatment. First anticancer drugs approved for clinical use were Vinca alkaloids, vinblastine and vincristine in the 1960s. They were isolated from extracts leaves of the Catharanthus roseus (Vinca rosea) plant at the University of Western Ontario in 1958. First drug belong to the taxanes and paclitaxel, discovered in extracts from the bark of the yew tree, Taxus brevifolia, in 1967 by Monroe Wall and Mansukh Wani but, its tubulin inhibition activity was not known until 1979. Yews trees are poor source of active agents that limited the development of taxanes for over 20 years until discover the way of synthesis. In December 1992 paclitaxel was approved to use in chemotherapy.

Tubulin and the microtubule system

Function

Microtubules are the key components of the cytoskeleton of eukaryotic cells and have an important role in various cellular functions such as intracellular migration and transport, cell shape maintenance, polarity, cell signaling and mitosis. They play a critical role in cell division by involving in the movement and attachment of the chromosomes during various stages of mitosis. Therefore, microtubule dynamics is an important target for the developing anti-cancer drugs.

Structure
Microtubules are composed of two globular protein subunits, α- and β-tubulin. These two subunits combine to form an α,β-heterodimer which then assembles in a filamentous tube-shaped structure. The tubulin hetero-dimers arrange themselves in a head to tail manner with the α-subunit of one dimer coming in contact with the β-subunit of the other. This arrangement results in the formation of long protein fibres called protofilaments. These protofilaments form the backbone of the hollow, cylindrical microtubule which is about 25 nanometers in diameter and varies from 200 nanometers to 25 micrometers in length. About 12–13 protofilaments arrange themselves in parallel to form a C-shaped protein sheet, which then curls around to give a pipe-like structure called the microtubule. The head to tail arrangement of the hetero dimers gives polarity to the resulting microtubule, which has an α-subunit at one end and a β-subunit at the other end. The α-tubulin end has negative (–) charges while the β-tubulin end has positive (+) charges.  The microtubule grows from discrete assembly sites in the cells called Microtubule organizing centers (MTOCs), which are a network of microtubule associated proteins (MAP).

Two molecules of energy rich guanosine triphosphate (GTP) are also important components of the microtubule structure. One molecule of GTP is tightly bound to the α-tubulin and is non-exchangeable whereas the other GTP molecule is bound to β-tubulin and can be easily exchanged with guanosine diphosphate (GDP). The stability of the microtubule will depend on whether the β-end is occupied by GTP or GDP. A microtubule having a GTP molecule at the β-end will be stable and continue to grow whereas a microtubule having a GDP molecule at the β-end will be unstable and will depolymerise rapidly.

Microtubule dynamics
Microtubules are not static but they are highly dynamic polymers and exhibit two kinds of dynamic behaviors : 'dynamic instability' and 'treadmilling'. Dynamic instability is a process in which the microtubule ends switches between periods of growth and shortening. The two ends are not equal, the α-tubulin ringed (-)end  is less dynamic while the more dynamic β-tubulin ringed (+) end grows and shortens more rapidly. Microtubule undergoes long periods of slow lengthening, brief periods of rapid shortening and also a pause in which there is neither growth nor shortening.
Dynamic instability is characterized by four variables:  the rate of microtubule growth;  the rate of shortening;  frequency of transition from the growth or paused state to shortening (called  a 'catastrophe') and the frequency of transition from shortening to growth or pause (called a 'rescue'). The other dynamic behavior called treadmilling  is the net growth of the microtubule at one end and the net shortening at the other end. It involves the intrinsic flow of tubulin sub-units from the plus end to the minus end. Both the dynamic behaviors are important and a particular microtubule may exhibit primarily dynamic instability, treadmilling or a mixture of both.

Mechanism of action

Agents which act as inhibitors of tubulin, also act as inhibitors of cell division.
A microtubule exists in a continuous dynamic state of growing and shortening by reversible association and dissociation of α/β-tubulin heterodimers at both the ends. This dynamic behavior and resulting control over the length of the microtubule is vital to the proper  functioning of the mitotic spindle in mitosis i.e., cell division.

Microtubule is involved in different stages of the cell cycle. During the first stage or prophase, the microtubules required for cell division begins to form and grow towards the newly formed chromosomes forming a bundle of microtubules called the mitotic spindle. During prometaphase and metaphase this spindle attaches itself to the chromosomes  at a particular point called the kinetochore and undergoes several growing and shortening periods in tuning  with the  back and forth oscillations of the chromosomes. In anaphase also, the microtubules attached to the chromosomes  maintain a carefully regulated shortening and lengthening process. Thus the presence of a drug which can suppress the microtubule dynamics is sufficient to block the cell cycle and result in the death of the cells by apoptosis.

Tubulin inhibitors thus act by interfering with the dynamics of the microtubule, i.e., growing (polymerization) and shortening (depolymerization). One class of inhibitors operate by inhibiting polymerization of tubulin to form microtubules  and are called polymerization inhibitors like the colchicine analogues and the vinca alkaloids. They decrease the microbule polymer mass in the cells at high concentration and act as microtubule-destabilizing agents. The other class of inhibitors operate by inhibiting the depolymerization of polymerized tubulin and increases the microtubule polymer mass in the cells. They  act as microbule-stabilizing agents and  are called depolymerization inhibitors like the paclitaxel analogues. These three classes of drugs seems to operate by slightly different mechanism.

Colchicine analogues blocks cell division by disrupting the microtubule. It has been reported that the β-subunit of tubulin is involved in colchicine binding. It binds to the soluble tubulin to form colchicine-tubulin complex.  This complex along  with the normal tubulins then undergoes polymerization to form  the microtubule. However the presence of this T-C complex prevents further polymerization of the microtubule . This complex brings about a conformational change which blocks the tubulin dimers  from further addition and thereby prevents the growth of the microtubule. As the T-C complex slows down the addition of new dimers, the microtubule disassembles due to structural imbalance or instability during the metaphase of mitosis.

The Vinca alkaloids bind to the β-subunit of tubulin dimers at a distinct region called the Vinca-binding domain. They bind to tubulin rapidly, and this binding is reversible and independent of temperature (between 0 °C and 37 °C). In contrast to colchicine, vinca alkaloids bind to the microtubule directly. They do not first form a complex  with the soluble tubulin nor do they  copolymerize to form the microtubule, however they are capable of bringing about a conformational change in tubulin in connection with tubulin self-association. Vinca alkaloids bind to the tubulin with high affinity at the microtubule ends but with low affinity at the tubulin sites present along the sides of the microtubule cylinder. The binding of these drugs at the high affinity sites results in strong kinetic  suppression of tubulin exchange even at low drug concentration while their  binding to the low affinity sites in relatively high drug concentration depolymerizes microtubules.

In contrast to colchicine and vinca alkaloids, paclitaxel enhances microtubule polymerization promoting both the nucleation and elongation phases of the polymerization reaction, and it reduces the critical  tubulin sub-unit concentration (i.e., soluble tubulin concentration at steady- state). Microtubules polymerized in presence of paclitaxel are extremely stable. The binding mechanism of the paclitaxel mimic that of the GTP nucleotide along with some important  differences. GTP binds at one end of the tubulin dimer keeping  contact with the next dimer along each of the protofilament while the paclitaxel  binds to one side of β-tubulin keeping contact with the next protofilament. GTP binds to unassembled tubulin dimers whereas paclitaxel binding sites are located only in assembled tubulin. The hydrolysis of GTP permits the disassembly and the regulation of the microtubule system; however, the activation of tubulin by paclitaxel results in permanent stabilization of the microtubule. Thus the suppression of microtubule dynamics was described to be the main cause of the inhibition of cell division and of tumor cell death in paclitaxel treated cells.

Tubulin binding drugs

Tubulin binding molecules have gained much  interest among cytotoxic agents due to its success in clinical oncology. They differ from the  other anticancer drugs in their mode of action because they target  the mitiotic spindle and not the DNA. Tubulin binding drugs have been classified on the basis of their mode of action and binding site as:

I. Tubulin depolymerization inhibitors

a) Paclitaxel site ligands, includes the paclitaxel, epothilone, docetaxel, discodermolide etc.

II. Tubulin polymerization inhibitors

a) Colchicine binding site, includes the colchicine, combrestatin, 2-methoxyestradiol, methoxy benzenesulfonamides (E7010) etc.

b) Vinca alkaloids binding site, includes vinblastine, vincristine, vinorelbine, vinfluine, dolastatins, halichondrins, hemiasterlins, cryptophysin 52, etc.

 Vinblastine and vincristine were isolated from the Madagascar periwinkle Catharanthus roseus. Madagascar traditionally used the vinca rosea to treat diabetes. In fact it has been used for centuries throughout the world to treat all kinds of ailments from wasp stings in India, to eye infections in the Caribbean. In the 1950s researchers began to analyse the plant and discovered that it contained over 70 alkaloids. Some were found to have effect on lower blood sugar levels and others act as hemostatics. The most interesting thing was that vinblastine and vincristine, were found to lower the number of white cells in blood. A high number of white cells in the blood indicates leukemia, so a new anti-cancer drug had been discovered. These two alkaloids bind to tubulin to prevent the cell from making the spindles that it needs to be able to divide. This is different from the action of taxol which interferes with cell division by keeping the spindles from being broken down. Vinblastine is mainly useful for treating Hodgkin's lymphoma, advanced testicular cancer and advanced breast cancer. Vincristine is mainly used to treat acute leukemia and other lymphomas.
 Vinorelbine was developed under the direction of the French pharmacist Pierre Poiter, who, in 1989, obtained an initial license for the dug under the brand name Navelbine. Vinorelbine is also known as vinorelbine tartrate, the drug is a semi-synthetic analogue of another cancer-fighting drug, vinblastine. Vinorelbine is included in the class of pharmaceuticals known as vinca alkaloids, and many of its characteristics mimic the chemistry and biological mechanisms of the cytotoxic drugs vincristine and vinblastine. Vinorelbine showed promising activity against breast cancer and is in clinical trial for the treatment of other types of tumors.
 Vinflunine is a novel fluorinated vinca alkaloid currently in Phase II clinical trials, which in preclinical studies exhibited superior antitumor activity to vinorelbine and vinblastine. Vinflunine block mitosis at the metaphase/anaphase transition, leading to apoptosis. Vinflunine is a chemotherapy drug used to treat advanced transitional cell bladder and urothelial tract cancer. It is also called Javlor. It is licensed for people who have already had cisplatin or carboplatin chemotherapy.
 Cryptophycin 52 was isolated from the blue–green algae Nostoc sp. GSV 224. The cryptophycins are a family of related depsipeptides showing highly potent cytotoxic activity. Cryptophycin 52 was originally developed as a fungicide, but was too toxic for clinical use. Later the research was focused on treating cryptophycin as a microtubule poison, preventing the formation of the mitotic spindle. Cryptophycin 52 showed high potent antimitotic activity to resist spindle microtubule dynamics. As well, the interest in this drug has been further arose by the discovery that cryptophycin shows reduced susceptibility to the multidrug resistance pump, and shows no reduction of activity in a number of drug-resistant cell lines.
 Halichondrin B was first isolated from Halichondria okadai, and later from the unrelated sponges Axinella carteri and Phankella carteri. Halichondrin B is a complex polyether macrolide which is synthesized and arrests cell growth at subnanomolar concentrations. Halichondrin B is noncompetitive inhibitor of the binding of both vincristine and vinblastine to tubulin, suggesting the drugs bind to the vinca binding site, or a site nearby. The isolation of halichondrin B is from two unrelated genera of sponge, has led to speculate that halichondrin B is a microbial in reality, rather than sponge metabolite because sponges support a wide range of microbes. If this is the case, fermentation technologies could provide a useful supply of halichondrin B.
 Dolastatins were isolated from the sea hare Dolabella auricularia, a small sea mollusc, and thought to be the source of poison used to murder the son of Emperor Claudius of Rome in 55 A.D. Dolastatins 10 and 15 are novel pentapeptides and exhibit powerful antimitotic properties. They are cytotoxic in a number of cell lines at subnanomolar concentrations. The peptides of dolastatins 10 and 15 noncompetitively inhibit the binding of vincristine to tubulin. Dolastatin 10 is 9 times more potent than dolastatin 15 and both are more potent than vinblastin. The dolastatins also enhance and stabilize the binding of colchicine to tubulin.
 Hemiasterlins were isolated from the marine sponge, Cymbastela sp. The hemiasterlins are a family of potent cytotoxic peptides. Hemiasterlin A and hemiasterlin B show potent activity against the P388 cell line and inhibit cell division by binding to the vinca alkaloid site on tubulin. Hemiasterlin A and B exhibit stronger antiproliferative activities than both the vinca alkaloids and paclitaxel.
 Colchicine an alkaloid prepared from the dried corns and seeds of the meadow saffron, Colchicum autumnale, is an anti-inflammatory drug that has been in continuous use for more than 3000 years. Colchicine is an oral drug, known to be used for treating acute gout and preventing acute attacks of familial Mediterranean fever (FMF). However, the use of colchicine is limited by its high toxicity in other therapies. Colchicine is known to inhibit cell division and proliferation. Early study demonstrated that colchicine disrupts the mitotic spindle. Dissolution of microtubules subsequently was shown to be responsible for the effect of colchicine on the mitotic spindle and cellular proliferation.
 Combretastatins is isolated from the South African Willow, Combretum caffrum. Combretastatin is one of the simpler compounds to show antimitotic effects by interaction with the colchicine binding site of tubulin, and is also one of the most potent inhibitors of colchicine binding. Combretastatin is not recognized by the multiple drug resistance (MDR) pump, a cellular pump which rapidly ejects foreign molecules from the cell. Combretastatin is also reported to be able to inhibit angiogenesis, a process essential for tumor growth. Except those factors, one of the disadvantage of combretastatin is the low water solubility.
 E7010 is the most active of sulfonamide antimitotic agent, which has been shown to inhibit microtubule formation by binding at the site of colchicines. It is quite soluble in water as an acid salt. Methoxybenzene-sulfonamide showed good results against a wide range of tumor cells including vinca alkaloid resistant solid tumors. Results from animals studies indicated activity against colorectal, breast and lung cancer tissues.
 2-Methoxyestradiol is a natural metabolite of the mammalian hormone oestradiol and is formed by oxidation in the liver. 2-methoxyestradiol is cytotoxic to several tumor cell lines, binds to the colchicine site of tubulin, inducing the formation of abnormal microtubules. 2-Methoxyestradiol exhibits potent apoptotic activity against rapidly growing tumor cells. It also has antiangiogenic activity through a direct apoptotic effect on endothelial cells.
 Docetaxel,  is a semi-synthetic analogue of paclitaxel, with a trade name Taxotere. Docetaxel has the minimal structure modifications at C13 side chain and C10 substitution showed more water solubility and more potency than paclitaxel. Clinical trials have shown that patients who develop hypersensitivity to paclitaxel may receive docetaxel without an allergic response.
 Paclitaxel was isolated from the bark of the Pacific yew tree Taxus brevifolia Nutt. (Taxaceae). Later it was also isolated from hazelnut trees (leaves, twigs, and nuts) and the fungi living on these trees but the concentration is only around 10% of the concentration in yew trees. Paclitaxel is also known as Taxol and Onxol to be an anti-cancer drug. The drug is the first line treatment for ovarian, breast, lung, and colon cancer and the second line treatment for   AIDS-related Kaposi's sarcoma. (Kaposi sarcoma is a cancer of the skin and mucous membranes that is commonly found in patients with acquired immunodeficiency syndrome, AIDS). It is so effective that some oncologists refer to the period before 1994 as the "pre-taxol" era for treating breast cancer.
 Epothilones  are derived from a fermenting soil bacteria, Sorangium cellulosum and it was found to be too toxic for use as an antifungal. Epothilones are microtubule stabilizing agents with a mechanism of action similar to taxanes, including suppression of microtubule dynamics, stabilization of microtubules, promotion of tubulin polymerization, and increased polymer mass at high concentrations. They induce mitotic arrest in the G2-M phase of the cell cycle, resulting in apoptosis. Epothilone A and epothilone B exhibit both antifungal and cytotoxic properties. These epothilones are competitive inhibitors of the binding of paclitaxel to tubulin, exhibiting activity at similar concentrations. This finding leads to assume that the epothilones and paclitaxel adopt similar conformations in vivo. However, the epothilones are around 30 times more water-soluble than paclitaxel and more available, being easily obtained by fermentation of the parent myxobacterium and could be prepared by total synthesis. The epothilones also shows not to be recognized by multidrug resistant mechanisms, therefore it has much higher potency than paclitaxel in multidrug resistant cell lines.
 Discodermolide was initially found to have immunosuppressive and antifungal activities. Discodermolide is a polyhydroxylated alketetraene lactone marine product, isolated from the Bahamian deep-sea sponge, Discodermia dissoluta, inhibited cell mitosis and induced formation of stable tubulin polymer in vitro and considered to be more effective than paclitaxel with EC50 value of 3.0μM versus 23μM. The drug, a macrolide (polyhydroxylated lactone), is a member of a structural diverse class of compounds called polyketides with notable chemical mechanism of action. It stabilizes the microtubules of target cells, essentially arresting them at a specific stage in the cell cycle and halting cell division. It is a promising marine-derived candidate for treating certain cancers.

Structure activity relationship (SAR)

Colchicine is one of the oldest known antimitotic drugs and in the past years much research has been done in order to isolate or develop compounds having similar structure but high activity and less toxicity. This resulted in the discovery of a number of colchicine analogues. The structure of colchicine is made up of three rings, a trimethoxy benzene ring (ring A), a methoxy tropone ring (ring C) and a seven-membered ring (ring B) with an acetamido group located at its C-7 position. The trimethoxy phenyl group of colchicine not only helps in stabilizing the tubulin-colchicine complex but is also important for antitubulin activity in conjunction with the ring C. The 3-methoxy group increased the binding ability whereas the 1-methoxy group helped in attaining the correct conformation of the molecule. The stability of the tropone ring and the position of the methoxy and carbonyl group are crucial for the binding ability of the compound. The 10-methoxy group can be replaced with halogen, alkyl, alkoxy or amino groups without affecting tubulin binding affinity, while bulky substituents reduce the activity. Ring B when expanded showed reduced activity, however the ring and its C-7 side chain is thought to affect the conformation of the colchicine analogues rather than their tubulin binding ability. Substitution at C-5 resulted in loss of activity whereas attachment of annulated heterocyclic ring systems to ring B resulted in highly potent compound.

Paclitaxel has achieved great success as an anti-cancer drug, yet there has been continuous effort to improve its efficacy and develop analogues which are more active and have greater bioavailability and specificity. The importance of C-13 substituted phenylisoserine side chain to bioactivity of paclitaxel has been known for a long time. Several replacements at the C-3' substitution have been tested. Replacement of the C-3' phenyl group with alkyl or alkyneyl groups greatly enhanced the activity, and with CF3 group at that position in combination with modification of the 10-Ac with other acyl groups increased the activity several times. Another modification of C-3' with cyclopropane and epoxide moieties were also found to be potent. Most of the analogues without ring A were found to be much less active than palitaxel itself. The analogues with amide side chain at C-13 are less active than their ester counterpart. Also deoxygenation at position 1 showed reduced activity. Preparation of 10-α-spiro epoxide and its 7-MOM ether gave compounds having comparable cytotoxicity and tubulin assembly activity as that of paclitaxel. Substitution with C-6-α-OH and C-6-β-OH gave analogues which were equipotent to paclitaxel in tubulin assembly assay. Finally the oxetane ring  is found to play an important role during interaction  with tubulin.

Vinblastine is a highly potent drug which also has serious side effects especially on the neurological system. Therefore, new synthetic analogues were developed with the goal of obtaining more efficient and less toxic drugs. The stereochemical configurations at C-20', C-16' and C-14' in the velbanamine portion are critical and inversion leads to loss of activity. The C-16' carboxymethyl group is important for activity since decarboxylated dimer is inactive. Structural variation at C-15'- C-20' in the velbanamine ring is well tolerated. The upper skeletal modification of  vinblastine gave vinorelbine which shows comparable activity as that of vinblastine. Another analogue prepared was the difluoro derivative of vinorelbine which showed improved in vivo antitumor activity. It was discovered that fluorination at C-19' position of vinorelbine dramatically increased the in vivo activity. Most of the SAR studies involve the vindoline portion of bis-indole alkaloids because modification at C-16 and C-17 offers good opportunities for developing new analogues. The replacement of the ester group with an amide group at the C-16 resulted in the development of vindesine. Similarly replacement of the acetyl group at C-16 with L-trp-OC2H5, d-Ala(P)-(OC2H5)2, L-Ala(P)-(OC2H5)2 and I-Vla(P)-(OC2H5)2 gave  rise to new analogues having anti- tubulin activity. Also it was found that the vindoline's indole methyl group is a useful position to functionalize potentially and develop new, potent vinblastine derivatives. A new series of semi-synthetic C-16 -spiro-oxazolidine-1,3-diones prepared from 17-deacetyl vinblastine showed good anti-tubulin activity and lower cytotoxicity. Vinglycinate a glycinate prodrug derived from the  C-17-OH group of vinblastine showed similar antitumor activity and toxicity as that of vinblastine.

Limitations

Side effects
 chemotherapy-induced peripheral neuropathy, a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.
 stomatitis (ulceration of the lips, tongue, oral cavity)
 nausea, vomiting, diarrhea, constipation, paralytic ileus, urinary retention
 bone marrow suppression
 hypersensitivity reactions – flushing, localized skin reactions, rash (with or without) pruritus, chest tightness, back pain, dyspnea, drug fever, or chills
 musculoskeletal effects – arthralgia and/or myalgia
 severe weakness
 hypotension
 alopecia
 neurotoxicity

Human factors
Limitations in anticancer therapy occur mainly due to two reasons; because of the patient's organism, or because of the specific genetic alterations in the tumor cells. From the patient, therapy is limited by poor absorption of a drug which can lead to low concentration of the active agent in the blood and small amount delivery to the tumor. Low serum level of a drug can be also caused by rapid metabolism and excretion associated with affinity to intestinal or/and liver cytochrome P450. Another reason is the instability and degradation of the drugs in gastro-intestinal environment. Serious problem is also variability between patients what causes different bioavailability after administration equal dose of a drug and different tolerance to effect of chemotherapy agents. The second problem is particularly important in treatment elderly people.  Their body is weaker and need to apply lower doses, often below therapeutic level. Another problem with anticancer agents is their limited aqueous solubility what substantially reduces absorption of a drug. Problems with delivery of drags to the tumor occur also when active agent has high molecular weight which limits tissue penetration or the tumor has large volume prevent for penetration.

Drug resistance
Multidrug resistance is the most important limitation in anticancer therapy. It can develop in many chemically distinct compounds. Until now, several mechanisms are known to develop the resistance. The most common is production of so-called "efflux pumps". The pumps remove drugs from tumor cells which lead to low drug concentration in the target, below therapeutic level. Efflux is caused by P-glycoprotein called also the multidrug transporter. This protein is a product of multidrug resistance gene MDR1 and a member of family of ATP-dependent transporters (ATP-binding cassette). P-glycoprotein occurs in every organism and serves to protect the body from xenobiotics and is involved in moving nutrients and other biologically important compounds inside one cell or between cells. P-glycoprotein detects substrates when they enter the plasma membrane and bind them which causes activation of one of the ATP-binding domains. The next step is hydrolysis of ATP, which leads to a change in the shape of P-gp and opens a channel through which the drug is pumped out of the cell. Hydrolysis of a second molecule of ATP results in closing of the channel and the cycle is repeated. P-glycoprotein has affinity to hydrophobic drugs with a positive charge or electrically neutral and is often over-expressed in many human cancers. Some tumors, e.g. lung cancer, do not over-express this transporter but also are able to develop the resistance. It was discovered that another transporter MRP1 also work as the efflux pump, but in this case substrates are negatively charged natural compounds or drugs modified by glutathione, conjugation, glycosylation, sulfation and glucuronylation.
Drugs can enter into a cell in few kinds of ways. Major routes are: diffusion across the plasma membrane, through receptor or transporter or by the endocytosis process. Cancer can develop the resistance by mutations to their cells which result in alterations in the surface of cells or in impaired endocytosis. Mutation can eliminate or change transporters or receptors which allows drugs to enter into the tumor cell.
Other cause of drug resistance is a mutation in β tubulin which cause alterations in binding sites and a given drug cannot be bound to its target. Tumors also change expression isoforms of tubulin for these ones, which are not targets for antimitotic drugs e.g. overexpress βIII-tubulin. In addition tumor cells express other kinds of proteins and change microtubule dynamic to counteract effect of anticancer drugs.
Drug resistance can also develop due to the interruption in therapy.

Others
 Marginal clinical efficacy – often compounds show activity in vitro but do not have antitumor activity in clinic.
 Poor water solubility of drugs which need to be dissolved in polyoxyethylated castor oil or polysorbate what cause hypersensitivity reactions. It has been suggested this solvents can also reduce delivery of the drugs to target cells.
 Bioavailability
 Dose limit – higher doses cause high toxicity and long-term use lead to cumulative neurotoxicity and hematopoietic toxicity.
 Neuropathy which is significant side effect can develop at any time in therapy and require an interruption of treatment. After symptoms have resolved therapy can be started again but the break allow tumor for develop of resistance.
 Poor penetration through the blood–brain barrier.

Future drug development
Because of numerous adverse effect and limitations in use, new drugs with better properties are needed. Especially are desired improvements in antitumor activity, toxicity profile, drug formulation and pharmacology.
Currently have been suggested few approaches in development of novel therapeutic agents with better properties
 Discovery agents which are not a substrate for efflux pump or modifications of drugs in toward lower affinity to transporting proteins. Discover P-glycoprotein inhibitors with higher affinity to the transporter then drugs, is next approach. For improving oral bioavailability is suggested co-administration of P-gp and cytochrome inhibitors with anticancer drugs.
 Development of inhibitors that have their binding site in α-tubulin. This part of tubulin dimer remains unused because all currently use drugs bind to the β-tubulin. Research in this field can open new opportunity in treatment and provide new class of inhibitors.
 One of the targets for anticancer drugs can be tumor vasculature. The advantage in this case is relatively easy access of therapeutic agents to the target. It is known that some compounds can inhibit the formation of new blood vessels (inhibit the process of angiogenesis) or shut down existing ones. Tumor cells die very fast after cutting off the oxygen supply what suggest these agents are especially interesting. What more, it seems the agents act only with tumor vasculature and do not interact with normal tissues. The mechanisms is not known but has been suggested that the reason are differences between young tissue of tumor and mature tissue of normal vasculature. Antivascular agents are similar to colchicine and bind to the colchicine binding site on β-tubulin so development of novel agents acting with colchicine binding site (which is not used by any of currently approved drugs) seems to be a promising approach.
 Therapy with combination of two or more drugs which have various binding sites and/or different mechanism of action but have non overlapping adverse effects. This would allow use of drugs in low concentration what reduce strength of side effects associated with high doses of anticancer agents. Better efficiency might be also a result of maintenance low concentrations of drugs for long period instead of drastic changes in the amount of administered drugs.
 Liposomes and polymer-bound drugs comprise promising improvements in delivery system. Liposomes allow for delivery considerable amounts of drag to the tumor without toxic effect in normal tissues and slowly release drugs what result in prolongation of pharmaceutical action. Similar properties have drugs bound to polymer. In addition, use of water-soluble polymers allow hydrophilic anticancer agents become soluble. The nature of polymer-drug linkage can be designed to be stable in normal tissues and break down in tumor environment, which is more acidic. This approach allow for release active agent exactly in the target.
 Discover new compounds active against drug-resistant cancers with different mechanism than drugs have been already known.
 Elucidation of all resistance mechanisms and design drugs which avoid it.

See also

 Tubulin
 Microtubule
 Cancer
 Chemotherapy
 Drug design
 Vinblastine
 Vincristine
 Vinorelbine
 Vinflunine
 Cryptophycin
 Halichondrin B
 Colchicine
 Combretastatins
 2-Methoxyestradiol
 Docetaxel
 Paclitaxel
 Epothilones
 Discodermolide
 eribulin, a newer agent

References

tubulin inhibitors
Category:Articles containing video clips
Category:Mitotic inhibitors


William L. Lane

William L. Lane (1931–1999) was an American New Testament theologian and professor of biblical studies.

Background and education
Lane has earned his B.A. from Wesleyan University, his M.Div. from Gordon Divinity School (1955), his Th.M. from Westminster Theological Seminary (1956), and his Th.D. from Harvard Divinity School.

Academic career
Lane began his academic career as professor of New Testament and Judaic studies at Gordon-Conwell Theological Seminary. He went on to serve as professor of religious studies at Western Kentucky University for fifteen years. During this time, he became a mentor to Christian singer and songwriter Michael Card. He was also recognized with the faculty award for "Distinguished Contributions in Research or Creativity" for the 1983–1984 academic year. Lane joined the faculty of Seattle Pacific University as dean of the School of Religion in 1989. He was named "Professor of the Year" by the student body in 1992, and served as the Paul T. Walls Chair in Wesleyan and Biblical Studies from 1993 until his retirement in 1997.

In addition to these roles, Lane also served as one of the translators of the New American Standard Bible, and the New International Version.

Death and legacy
In retirement, Lane moved with his wife to Franklin, Tennessee, where they established a residential biblical research library and discipleship center. Lane died in the research library he came to Franklin to establish. Nashville, Tennessee, on March 8, 1999.

Publications
Lane was the author or editor of several notable works, including The Encyclopedia of Modern Christian Missions (1967), The New Testament Speaks (1969), The Gospel According to Mark in The New International Commentary on the New Testament (1974), and the two-volume commentary on the  Epistle to the Hebrews in the Word Biblical Commentary (1991), which was awarded the 1993 Christianity Today Critic's Choice for "Book of the Year".

Works

Books

Editorial

Articles

References

Category:1931 births
Category:1999 deaths
Category:American theologians
Category:New Testament scholars
Category:Translators of the Bible into English
Category:Seattle Pacific University faculty
Category:Western Kentucky University faculty
Category:Gordon-Conwell Theological Seminary faculty
Category:Westminster Theological Seminary alumni
Category:Harvard Divinity School alumni
Category:Wesleyan University alumni
Category:20th-century translators
Category:Bible commentators
Category:American translators


Telecrates tesselata

Telecrates tesselata is a moth in the family Xyloryctidae. It was described by Lucas in 1900. It is found in Australia, where it has been recorded from Queensland.

The wingspan is about 20 mm. The forewings have a large pear shape blotch of white from the costa at the base widening to the inner margin and a second cream white blotch from one-eighth to one-fourth the costa, obliquely outward to the middle of the wing. There is a third blotch from before the middle to half the costa as a band across the wing, widening out beyond the middle, and filling the inner margin from half to three-fourths the inner margin, the edge rounded and finely dentate. A fourth blotch is found to three-fourths the costa, reaching half across the wing, the posterior border twice dentate. There is also a hindmarginal narrow band drawn to a line to the anal angle. The hindwings are ochreous yellow diffused with fuscous along hindmargin chiefly over the apex.

References

Category:Telecrates
Category:Moths described in 1900


Robert Clark (businessman)

Sir Robert Anthony "Bob" Clark DSC (6 January 1924 – 3 January 2013) was a British naval officer and businessman.  Clark attended King's College, Cambridge before leaving at the age of 18 to join the Royal Naval Volunteer Reserve during the Second World War.  Discovered to be colour blind he was relegated to non-seagoing posts, a prospect he found unappealing.  He volunteered for service with the Special Operations Executive and saw active service in Italy, first on amphibious missions and later as a liaison officer with partisans in the Piedmont Mountains.  Clark was captured by the Germans, and was later awarded the Distinguished Service Cross for his gallantry.

A chance meeting after the war led to a position at the law firm of Slaughter & May, where he was soon made a partner.  He switched career to become a merchant banker with Hill Samuel, where he developed an expertise in company mergers and acquisitions.  Clark acted as chairman or director for numerous firms and sat on many governments bodies and committees.  Clark met Robert Maxwell in 1969 when Maxwell attempted to outbid Rupert Murdoch for the News of the World, starting a lifelong acquaintance.  He led Hill Samuel through their takeover by TSB before Maxwell brought him on as a non-executive director at his Mirror Group of media companies.

Clark became embroiled in the scandal at the Mirror Group that unfolded after Maxwell's death in 1991.  Clark claimed to be ignorant of Maxwell's £492 million defrauding of the company and its pension scheme, and faced a non-confidence vote by the shareholders.  He survived to be made chairman of the group and to rebuild it after the scandal.

Early life
Bob Clark was born on 6 January 1924 in Finchley, London. His parents were Gladys and Jack Clark, his father being a mechanical engineer who was once apprenticed to Sir Charles Parsons. Clark attended Highgate School in London and was evacuated with the school to Westward Ho! in Devon on the outbreak of the Second World War. Clark was a keen football player and was captain of the Highgate team as well as being head boy of the school. He went up to King's College, Cambridge to study modern languages.  Whilst there he gained a blue in football, the first from the college in 20 years, and played against their rivals at Oxford University.

Navy career

Clark left Cambridge at the age of 18 to join the Royal Naval Volunteer Reserve as an officer. During initial training at HMS Collingwood, near Portsmouth, Clark discovered that he was colour blind and only passed the medical examination by persuading the man sitting behind him to whisper the answers to him. Clark served aboard  on convoy escort operations in the Atlantic and Mediterranean before attending HMS King Alfred at Hove. Whilst there his colour blindness was discovered and he was banned from seagoing postings.

Frustrated at not being able to fight the enemy directly, Clark volunteered for service with the Special Operations Executive (SOE), an irregular warfare unit, in June 1943, having claimed to have had experience working with small boats. He undertook commando training at Arisaig in the Scottish Highlands and further SOE training at Helford in Cornwall. After completing his training, Clark was dispatched to Algeria in September 1943 and thence to Monopoli in south-east Italy in December. He was attached to the SOE's No 1 Special Force and undertook amphibious sabotage, reconnaissance operations and running of agents into enemy-held beaches by canoe. His wireless operator for these missions was Marjorie Lewis, his future wife, who had joined the First Aid Nursing Yeomanry (FANY; often used as a cover for women who joined SOE) in 1943. On 1 March 1944 Clark, who had previously only held the acting rank of sub-lieutenant, was confirmed in a substantive (though temporary) rank.

Clark volunteered for parachute training with SOE and was subsequently allocated to Operation Clarion, the designation for British assistance provided to anti-German partisans in northern Italy. He parachuted into the Piedmont Mountains, south of Turin, in November 1944 with a radio operator, Petty Officer Edward Cauvain, to act as liaison officer to the partisans there. When Clark made his parachute jump he had Falla, his childhood teddy bear, inside his battledress for comfort and good luck. Despite this, he landed  off course and into a tree, breaking two ribs. Clark was rescued by a local partisan, Sergio Curetti of the 3rd Division of Italian partisans.

Clark set about arming the resistance and training them in methods of warfare. He had been instructed to avoid arming the communists where possible, his superiors fearing for their actions after the war, but finding the communists to be the most organised and well-motivated group in his area proceeded to arm them anyway. He arranged an air drop of arms and explosives, and led the partisans on several railway sabotage expeditions. Clark later recalled that "blowing up railway engines was very great fun". For his work with the partisans he was awarded the Distinguished Service Cross, the third-highest award for gallantry in the Royal Navy. Clark was betrayed and captured by a German patrol in December 1944 whilst trying to hide in a haystack with four partisans.

Clark managed to avoid summary execution at the hands of the Germans and was held in several Italian prisons where he was interrogated frequently. He was later transferred to the Marlag und Milag Nord prisoner of war camp near Bremen. Marjorie Lewis did not know that Clark was still alive until he sent her an uncoded message, strictly against standing SOE orders, reading "Bob sends love to Marjorie". After the camp was liberated Clark returned to London, sending ahead a telegram to Marjorie, stating: "Arriving London from Germany. Meet me". They met and the two shook hands; they were later married in 1949.  Clark's teddy bear Falla, which he had had since the age of two, had accompanied him throughout his time as a prisoner and is thought to be the only teddy bear to have parachuted behind enemy lines and survived as a prisoner of war.  Clark served in the Pacific Theatre and was promoted to lieutenant on 1 March 1946 before he was demobilised later that year.

Post-war
Clark intended to move to Sudan after the war but a chance meeting with his old commanding officer, Hilary Scott, in St James's led to him being offered a position as a clerk at the law firm of Slaughter & May. Clark later said of the meeting: "I knew nothing about the law, but I accepted. And luck worked."  He proved to be skilled at arranging mergers of companies and within six years of joining the firm was made a partner, at the age of 29 years.  At Slaughter & May, Clark worked exclusively for the firm's merchant bank clients and was involved in the bitter takeover of Millspaugh by Hadfield.  In 1957 Clark became a director of Marchwiel Holdings, better known as Alfred McAlpine the civil engineering firm, and would remain on their board until 1996.

Through his work Clark became acquainted with the partners of the Philip Hill, Higginson, Erlanders merchant bank (later known as Hill Samuel), one of the two largest in the country. The three men were all over   tall, "frightfully clever" and looking for a fourth partner.  Clark, a tall man himself, fitted their apparent criteria and in 1961 accepted the fourth partnership at the bank; he retired from his partnership at Slaughter & May on 30 September 1961. At Hill Samuel he headed the issues and mergers department and advised on some of the largest company mergers in British history. Clark handled the General Electric Company plc's takeovers of Associated Electrical Industries and English Electric under Arnold Weinstock, and the expansions of Racal, Beecham Group and Courtaulds. He also worked to win the firm business abroad. In 1967 he acted for the Astor family in the sale of The Times newspaper to Lord Thomson of Fleet. With the parties deadlocked and the final price disputed by £50,000, Clark successfully reached an agreement by flipping a coin.  He correctly called the fall and won the Astors the additional £50,000.  Clark kept the half-crown he had used as a memento and had it mounted on a silver stand. Clark helped to draft the 1968 City Takeover Code that remains in force and regulates how takeovers are carried out in British companies. He chaired the National Film Finance Corporation from 1969 to 1976 and sat on a committee to represent Rolls-Royce's creditors during the nationalisation process. Clark worked with Robert Maxwell when he attempted to purchase the News of the World in 1969.  Maxwell was beaten by his rival, Rupert Murdoch (whom Clark sued for libel during the course of the bid), but became friends with Clark and retained him as banker to his British Printing Corporation.

Clark chaired the government's Industrial Development Advisory Board from 1973 to 1980. In this position he found himself frustrated by Secretary of State for Industry Tony Benn's decision to ignore the board's advice and found workers' co-operative schemes at struggling firms Triumph Engineering and Fisher-Bendix in the early 1970s. Clark decided not to resign but to stay on and try to restrain Benn in the future. Benn bore him no ill-will for this and in 1974 asked him to join the government committee into the future of ailing car-makers Austin and British Leyland. He agreed to take the chair of Leyland in 1976 as a stop-gap measure but ended up holding the post for more than a year before the company, beset with strikes, nationalised and he handed the chair to Michael Edwardes. Clark remained a board member and in 1986 undertook discussions with General Motors in an attempt to get an increased bid for Leyland Vehicles, a bid later stopped by public outcry over the inclusion of the Land Rover name.

Clark became chairman of Hill Samuel Bank in 1974, a post he would hold until 1987. He was knighted on 10 February 1976, receiving the honour from the Queen at Buckingham Palace, and became a director of the Bank of England on 4 June, following the death of Sir John Norman Valette Duncan. He was subsequently reappointed director for the four-year terms beginning 1 March 1977 and 1 March 1981.

Clark was appointed chief executive officer of the Hill Samuel holding group in 1976 and was chairman from 1980 to 1988. Clark refused a takeover by Merrill Lynch, but after deregulation in 1986 he was convinced that Hill Samuel was not large enough to compete and, facing hostile takeovers from Kerry Packer and FAI Insurance, arranged takeover talks first with UBS and then with TSB. TSB acquired Hill Samuel in 1988, and Clark became a director in 1987 and then deputy chairman in 1989 for two years. He was on the boards of many other companies, holding directorships at Eagle Star (1976 to 1987) Royal Dutch Shell (1982 to 1994), Vodafone (1988 to 1998), IMI (1981 to 1989) and Marley (1985 to 1989) – he later became the first non-family chairman of the latter. He served on the Review Body on Doctors' and Dentists' Remuneration from 1979 to 1986 and was a trustee of the Charing Cross and Westminster Medical School from 1981 to 1995. In 1982 he received an honorary Doctorate of Science from the Cranfield Institute of Technology. Clark was appointed vice-chairman of pharmaceutical firm SmithKline Beecham in 1987, a post he held for eight years. He was also chairman of the United Drapery Stores, where he was responsible for refusing a takeover bid from Heron Foods before accepting one made by Hanson plc.

Mirror Group
Maxwell bought the Mirror Group in 1986 and floated it in May 1991, appointing Clark to the board of directors. Maxwell claimed that the offer he made Clark would appeal to even a "one-eyed Bulgarian peasant". Clark claimed that he tried to make Maxwell follow conventional business practices and remained convinced that "until quite close to the end, he never did anything I asked him not to do". It was only after Maxwell's unusual death on 5 November 1991 that financial mismanagement of the Mirror Group came to light. There was evidence of 29 unusual payments of £230 million from Mirror to other Maxwell companies within one year in a fraud that eventually cost the company, and its pension fund, £492 million. Clark claimed that there had been no evidence for the directors to act on against Maxwell, telling the shareholders at an extraordinary general meeting (EGM) that "No system of internal control, however elaborate, can stop fraudulent collusion by a group of individuals holding authority and trust. None of us [directors] would have taken on the job had we thought Maxwell was a crook. How many can stand up and say: 'We said he was a crook a year ago'?"  Clark's position was disputed by the Department of Trade and Industry, which determined that the two non-executive directors, Clark and Alan Clements, should have questioned the payments. At the EGM Clark almost lost his usual polite nature when he was accused of being a Maxwell "crony" by Rupert Allason and had to rule a no-confidence vote as out of order.

The liquidators of the Mirror asked him to stay on to clean up the company, and he was made chairman and Clements became deputy chairman. Clark brought in David Montgomery as chief executive officer and Lord Hollick as a director to rebuild the company.  Hollick remained for just five months before he fell out with Clark, who said: "He mistook politeness for weakness. It is always a big mistake."

Clark eventually stabilised the company and left as chairman in 1998.  He co-founded the RP&C International (Rauscher Pierce & Clark) investment bank in 1993 and remained a director until his death. He raised enough for a 25% stake and partnered with a Texas bank to provide the rest. Clark was also deputy chairman of Fenchurch from 1992 to 1995 and remained on its board until 1998. He chaired insurance broker Lownes Lambertin, formerly part of Hill Samuel, in 1995.

Personal life

Clark and his family lived for almost 50 years at a house in Surrey, the former home of horticulturist Gertrude Jekyll, that had been designed by Edwin Lutyens and which Clark described as "the best investment I ever made". Clark was a keen antiquarian, collecting old books and keeping a record of each one that he read. He maintained an interest in sport as well as the opera, having acted as director of the English National Opera from 1983 to 1987. He collected teddy bears, having more than 300 in total (including Falla), and was also interested in the life of Captain Cook, retracing one of his voyages himself. Clark was vice-chairman of the Salisbury Cathedral spire appeal. He was contacted in 1991 by Curetti, the Italian partisan who first helped him out of a tree in the war, and the pair visited each other regularly thereafter. Clark died on 3 January 2013.

References

Category:1924 births
Category:2013 deaths
Category:Recipients of the Distinguished Service Cross (United Kingdom)
Category:Knights Bachelor
Category:Royal Naval Volunteer Reserve personnel of World War II
Category:British Special Operations Executive personnel
Category:Alumni of King's College, Cambridge
Category:British bankers
Category:People educated at Highgate School


Torsö (crater)

Torsö Crater is a small impact crater in the Argyre quadrangle of Mars, located at 44.29° S and 51.18° W. It is 15.3 km in diameter. Its name was approved in 1976 by the International Astronomical Union (IAU) Working Group for Planetary System Nomenclature (WGPSN), and refers to a town in Sweden. Along the rim of Torsö Crater, a number of gullies are visible.

See also
 List of craters on Mars: O-Z

References

Category:Impact craters on Mars
Category:Argyre quadrangle


Ram Singh Bishnoi

Ram Singh Vishnoi was an Indian National Congress politician and senior leader from Rajasthan, India. He was an MLA from Luni constituency for seven times.. His grandson Mahendra Bishnoi is currently an MLA from Luni.

Personal life
Ram Singh Vishnoi was born in village Tilwasni, Bilara, Jodhpur. he was married to Amri devi Bishnoi. Former Luni MLA Malkhan Singh is his son

See also
 Mahendra Bishnoi
Luni VidhanSabha
Bishnoi Political Family

References

Category:Members of the Rajasthan Legislative Assembly
Category:1951 births
Category:2004 deaths
Category:Indian National Congress politicians from Rajasthan


If You Are the One 2

If You Are the One 2 (Chinese: 非诚勿扰2) is a 2010 Chinese film directed by Feng Xiaogang. It is the sequel to the 2008 film If You Are the One.

Plot
Qin (Ge You) and Liang (Shu Qi) question their relationship after watching their friends' lavish divorce ceremony.

Cast
Ge You
Shu Qi
Yao Chen
Sun Honglei
Ady An
Liao Fan
Zhao Bing
Feng Shaofeng
Guan Xiaotong
Zhang Hanyu
Zhao Baogang
Wu Yicong

References

External links

Category:Chinese films
Category:Films directed by Feng Xiaogang
Category:Films with screenplays by Wang Shuo
Category:Huayi Brothers films

Category:Chinese romantic comedy films


Luciano José Cabral Duarte

Luciano José Cabral Duarte (January 21, 1925 – May 29, 2018) was a Brazilian prelate of the Roman Catholic Church. He served as auxiliary bishop of Aracajú from 1966 till 1971, when he became archbishop of Aracajú. He resigned in 1998 and was succeeded by José Palmeira Lessa. He was professor of philosophy and one of the founders at the Federal University of Sergipe.

Life
Luciano José Cabral Duarte was the son of José de Góes Duarte and Célia Cabral. He was baptized in the Diocesan Cathedral, in Aracaju, on February 7, 1925.

He studied at the School of Apprentice Crafts, then Technical School, now IFS, before joining the Minor Seminary of the Sacred Heart of Jesus at the age of 11. He was always the first in the class. In 1942, he moved to the Seminary of Olinda, in Pernambuco. In February 1945 he transferred to St. Leopold (Rio Grande do Sul) where he completed the ecclesiastical studies necessary to become a priest.

He was ordained ordained to the priesthood on January 18, 1948. On July 14, 1966, he was appointed auxiliary bishop of Aracajú and titular bishop of Gadiaufala. Palmeira Lessa received his episcopal consecration on the following October 2 from José Vicente Távora, archbishop of Aracajú, with the bishop of Estância, José Bezerra Coutinho, and the bishop of Propriá, José Brandão de Castro, serving as co-consecrators. He took the motto "Scio Cui Credidi". On February 12, 1971, he was appointed archbishop of Aracajú. He retired on August 26, 1998, and was succeeded by José Palmeira Lessa.

Cabral Duartelived at his residence in Aracaju, due to his fragile state of health, until he died in the afternoon of May 29, 2018, at the age of 93.

Publications
Europa, Ver e Olhar. Aracaju : Sociedade de Cultura Artística De Sergipe/Livraria Regina, 1960
Europa e Europeus. São Paulo: Livraria Edurora Flamboyant, 1961 (reedição de Europa, ver e Olhar)
Viagem aos Estados Unidos. Aracaju: Sociedade Artística de Sergipe/ Livraria Regina, 1962
Índia a Vôo de Pássaro. Aracaju : Sociedade Artística de Sergipe/Livraria Regina, 1970
Estrada de Emaús. Petrópolis, RJ: Editora Vozes Ltda., 1971
A Igreja às Portas do Ano 2000
"La Nature de l'intelligence dans le thomisme et dans la philosophie de Hume"(Tese de doutorado em Filosofia, na Sorbone)

References

External links
 Entry about Luciano José Cabral Duarte at catholic-hierarchy.org

Category:1925 births
Category:2018 deaths
Category:People from Aracaju
Category:20th-century Roman Catholic bishops
Category:21st-century Roman Catholic bishops
Category:Brazilian Roman Catholic archbishops


WAPI

WAPI may refer to:

 WAPI (AM), a radio station (1070 AM) licensed to Birmingham, Alabama, United States
 WVTM, a television station (channel 13) licensed to Birmingham, Alabama, United States, which held the call sign WAPI-TV from 1958 to 1980
 WJQX, a radio station (100.5 FM) licensed to Helena, Alabama, which held the call sign WAPI-FM from 2010 to 2013
 Warsteiner Premium Pilsener, a German beer
 Washington Asian Pacific Islander Community Services
 Water Pasteurization Indicator
 WLAN Authentication and Privacy Infrastructure, a Chinese national standard for wireless LANs
 Workflow APIs and Interchange Formats, a specification from the Workflow Management Coalition (WfMC)
 World Association of Professional Investigators
 Wapi Rural LLG in Papua New Guinea
 WAPI, ICAO code for Mathilda Batlayeri Airport


Norman Thomas (disambiguation)

Norman Thomas may refer to:

 Norman Thomas (1884–1968), American socialist, pacifist and presidential candidate for the Socialist Party of America
Normam Thomas of the Norman Thomas Quintette, a vaudeville act that was also filmed by Vitaphone
 Norman G. Thomas (born 1930), American astronomer
 Norman Thomas (Australian politician) (1894–?), New South Wales politician
 Norman Thomas (broadcaster) (1947/8–2011), British radio personality

See also


Ennismore

Ennismore is the second solo studio album by the English singer Colin Blunstone of rock band the Zombies. It was originally released in November 1972 on the label Epic. The lead single "I Don't Believe in Miracles" peaked at No. 31 on the UK Singles Chart, and "How Could We Dare to Be Wrong" peaked No. 45. Ennismore was reissued on CD by Sony in 2003.

As with Blunstone's 1971 debut album One Year, Ennismore was produced by Rod Argent and Chris White and most of the songs were backed by Argent's band Argent.

Critical reception

Robin Platts of AllMusic retrospectively gave the album four out of five stars and wrote that "Opinions differ as to which of the two is Blunstone's best album, but both One Year and Ennismore are consistently strong records and are bound to please anyone who has enjoyed Colin's work with the Zombies."

Track listing
"I Don't Believe in Miracles" (Russ Ballard) – 3:03
"Quartet: Exclusively for Me" (Colin Blunstone, David Jones) – 2:30
"Quartet: A Sign from Me to You" (Blunstone) – 3:58
"Quartet: Every Sound I Heard" (Blunstone, David Jones) – 2:26
"Quartet: How Wrong Can One Man Be" (Blunstone) – 2:02
"I Want Some More" (Blunstone) – 3:08
"Pay Me Later" (Blunstone, Phil Dennys) – 2:46
"Andorra" (Rod Argent, Chris White) – 3:18
"I've Always Had You" (Blunstone) – 2:32
"Time's Running Out" (Blunstone) – 2:41
"How Could We Dare to Be Wrong" (Blunstone, Phil Dennys) – 3:24

Personnel
Colin Blunstone – vocals; guitar
Rod Argent – piano; keyboards
Russ Ballard – guitar; piano; keyboards
Steve Bingham – bass guitar
Jim Rodford – bass guitar
Robert Henrit – drums
Byron Lye Foot – drums
Jim Toomey – drums
Terry Poole – drums; bass guitar
Phil Dennys – piano; keyboards
Pete Wingfield – piano; keyboards
Derek Griffiths – guitar
Michael Snow – guitar; keyboards

Production
Rod Argent – producer
Chris White – producer
Peter Vince – engineer
Steve Campbell – cover photography
Chris Gunning – string arrangements
Dan Loggins – adviser
David Lowe – photography

References

External links

Category:1972 albums
Category:Colin Blunstone albums
Category:Albums recorded at Abbey Road Studios
Category:Albums produced by Rod Argent
Category:Albums produced by Chris White (musician)
Category:Epic Records albums


Dorothy May De Lany

Dorothy May De Lany (24 March 1908–19 October 1970) was a New Zealand hotel worker and trade unionist. She was born in Bluff, Southland, New Zealand on 24 March 1908.

References

Category:1908 births
Category:1970 deaths
Category:New Zealand trade unionists
Category:People from Bluff, New Zealand


Wenzl

Wenzl may refer to:

 Wenzl (surname)
 Birman–Wenzl algebra, family of algebras