title: Rishon LeZion

text: Founded in 1882 by Jewish immigrants from the Russian Empire who were part of the First Aliyah, it was the first Zionist settlement founded in the Land of Israel by the New Yishuv and the second Jewish farm settlement established in Ottoman Syria in the 19th century, after Petah Tikva. As of 2017, it was the fourth-largest city in Israel, with a population of .


title: Rishon LeZion

text: The city is a member of Forum 15, which is an association of fiscally autonomous cities in Israel that do not depend on national balancing or development grants.


title: Rishon LeZion

text: The name Rishon LeZion is derived from a verse from the Tanakh: "First to Zion are they, and I shall give herald to Jerusalem" (Isaiah 41:27) and literally translates as "First to Zion".


title: Rishon LeZion

text: Rishon LeZion was founded on 31 July 1882, by ten Hovevei Zion pioneers from Kharkiv, Ukraine (then the Russian Empire) headed by Zalman David Levontin. Reuven Yudalevich was also a member of the group. The British vice-consul in Jaffa, Haim Amzaleg, purchased of land southeast of present-day Tel Aviv, the site of watering holes called ‘Uyūn Qārā (literally 'fountain of the crier') from Mustafa Abdallah ali Dajan. According to Marom, ‘Uyūn Qārā offered "a convenient launching pad for early land purchase initiatives which shaped the pattern of Jewish settlement until the beginning of the British Mandate". Amzaleg signed a declaration to the settlers stating that none of the structures on this land will ever be his own.


title: Rishon LeZion

text: In addition to the problems posed by sandy soil and lack of water, the newcomers had no agricultural experience. Baron Rothschild brought in experts who drilled for water, finding the groundwater table uneven. Wells were built at a depth of 20–25 meters.


title: Rishon LeZion

text: After the Biluim arrived, the colony slowly began to develop. On 23 February 1883, the settlers found water in the wells. To mark this occasion, the village emblem was inscribed with a verse from the Torah: "We have found water." (Genesis 26:32) Fani Belkind, Israel Belkind, Shimshon Belkind, Yoel Drubin, Haim Hissin, and David Yudilovich were among the Biluim who arrived in Rishon Lezion at this time.


title: Rishon LeZion

text: In 1883, Itzhak Leib Toporovski a blacksmith of the young village created the first iron plow in the land of Israel, and in 1885 the flag that would later become the flag of Israel was raised for the first time as part of the celebrations of the 3rd anniversary of the village.


title: Rishon LeZion

text: When Baron Edmond James de Rothschild took over, sending in his administrators and agricultural guide Shaul Helzner of Mikve Israel, major progress was made in the spheres of agriculture, citrus and viticulture. In November 1883 the first rows were planted, led by ten Russian farmers who were further trained at Mikveh Israel agriculture school, also funded in part by Rothschild. The Great Synagogue, which became a major focus of life in Rishon LeZion, was built between 1885 and 1889. Under Rothschild's patronage, the Carmel-Mizrahi Winery was, established in 1886. The Baron Edmond James de Rothschild and his wife Adelheid von Rothschild came to visit the village a year later in 1887.


title: Rishon LeZion

text: In 1886, as Rishon LeZion's population of around 300 included several dozen children who required proper education, the Haviv elementary school was established in Rishon LeZion as the first modern school to teach exclusively in Hebrew. Dov Lubman Haviv taught there and Mordechai Lubman Haviv was an educational inspector. Eliezer Ben-Yehuda, the leading figure in the revival of Hebrew, was a teacher in Rishon LeZion. In 1898, the first Hebrew kindergarten in the world was established by Esther (Shapira) Ginzburg a former student of the Haviv school.


title: Rishon LeZion

text: Naphtali Herz Imber, the later famed Hebrew language poet, lived in Rishon LeZion for a few years in the late 1880s. He recited his poem, Tikvahtenu, to eager ears. In 1887, Shmuel Cohen, a young resident of Rishon with a musical background, observed the emotional response of the local Jewish farmers to Imber's poem. Using his musical skill, he put the poem to music. Cohen's musical composition was an adaptation of a Moldavian/Romanian folk-song, "Carcul cu Boi" ("the Cart with Oxen"). The catalyst of Cohen's musical adaptation facilitated the quick, enthusiastic spread of Imber's poem throughout all the Zionist communities of Palestine. Within a short few years, it spread globally to pro-Zionist communities and organizations becoming the unofficial Zionist National Anthem.


title: Rishon LeZion

text: In 1933, at the 18th Zionist Congress in Prague, the Imber/Cohen Zionist National Anthem, formally adopted, was renamed the Hatikvah (The Hope). In November 2004, the State of Israel formally adopted Shmuel Cohen's 1887 musical adaptation to a newly shortened, modified version of Imber's poem, creating the modern Israeli National Anthem, the Hatikvah.


title: Rishon LeZion

text: In 1888, the medicine house, the baron's stables and the baron's clerks house were built. In 1889 the building in which the Carmel-Mizrahi Winery is located was built. A telephone was added to the winery in 1891 and in 1898 electricity was installed. In 1890, a palm boulevard was planted in the location of the future city park. The Rishon LeZion orchestra was established in 1895. In 1898, the year Theodor Herzl visited the settlement, the city park (then the village park) was established and a water tower was built next to the well.


title: Rishon LeZion

text: At the year of its founding in 1882, Rishon LeZion had a population of 150. In 1890, Rishon LeZion had a population of 359. Five years later, the figure had risen to 380, and by 1900, to 526.


title: Rishon LeZion

text: In 1900, the management of the village was transferred from the baron's office to the village council and the Jewish Colonization Association. Israel's first Prime Minister, David Ben-Gurion, worked in the winery for two months in the summer of 1907.


title: Rishon LeZion

text: In 1910, the village bell was constructed next to the medicine house, and in 1912 the first car ("First chariot without horses") appeared in the village. In 1911, 4,000 dunams of land in Rishon LeZion were planted with grapes and 254 dunams with other fruit orchards.


title: Rishon LeZion

text: In 1913, the governor of Greater Syria, Djemal Pasha, annexed the sands around Rishon Lezion to their territory and in 1915 Rishon Lezion was expanded again and was given the territory between it and the Mediterranean Sea. In 1913, Nahlat Yehuda, another Jewish settlement, was established north of Rishon Lezion. In 1915 Rishon Lezion and the surrounding area experienced a Locust attack.


title: Rishon LeZion

text: Ayun Kara was the scene of a bloody battle between Turkish and New Zealand troops on 14 November 1917. Local citizens carried the wounded to a medical facility in Rishon LeZion. A stone cenotaph was erected by the people of Rishon LeZion to the memory of the New Zealanders who fell that day, but it has since been destroyed.


title: Rishon LeZion

text: In the wake of the battle, the New Zealanders set up camp at Rishon Lezion, which was described by one officer as a "pretty little hamlet surrounded by vineyards and orange groves." Relations between the troops and villagers were good, and the troops brought the villagers the news of the Balfour Declaration.


title: Rishon LeZion

text: In 1919, the women of Rishon Lezion were given voting rights and on the same year Nehama Pohatchevsky was elected chairman of the village council which marked the first time a woman was elected to the position.


title: Rishon LeZion

text: In 1924, the British Army contracted the Jaffa Electric Company for wired electric power to the military installations in Sarafand. The contract allowed the Electric Company to extend the grid beyond the original geographical limits that had been projected by the concession it was given. The high-tension line that exceeded the limits of the original concession ran along some major towns and agricultural settlements, offering extended connections to the Jewish settlements of Rishon Le-Zion, Nes-Ziona and Rehovot (in spite of their proximity to the high-tension line, the Arab towns of Ramleh and Lydda remained unconnected). According to a census conducted in 1922 by the British Mandate authorities, Rishon LeZion had a population of 1,396 inhabitants, consisting of 1,373 Jews and 23 Muslims, increasing in 1931 census to 2,525 inhabitants, in 648 houses.


title: Rishon LeZion

text: Rishon LeZion was declared a city in 1950, by which time it had a population of around 18,000. By 1983 it had a population of 103,000. In 2006, 222,300 people were living in the city. By 2020, the population is expected to reach 253,600. In 2007, the Rishon LeZion Municipality was awarded the Ministry of Interior Prize for Proper Management.


title: Rishon LeZion

text: In 2016, the Israeli government approved the expansion of Rishon LeZion onto sand dunes west of the city, upon which one of the largest commercial and residential construction projects in the Central District will be built on 1,000 dunams. Another industrial zone in the western part of the city is planned to be almost doubled in size.


title: Rishon LeZion

text: The 1922 Census conducted by the British Mandate authorities found there were 1,373 Jews living in Rishon LeZion and 23 Muslims.


title: Rishon LeZion

text: According to data from the Israel Central Bureau of Statistics as of December , the number of residents in Rishon LeZion is . Rishon LeZion is one of the fastest-growing cities in Israel, and is third-youngest city in the country, after Jerusalem and Bnei Brak, with 31.1% of the population being children and teenagers, and 61.4% of all residents being aged 40 or under. In addition, the city has attracted significant immigration, including from English-speaking countries. The city is expected to have a population of around 270,000 by 2030. Its population growth rate is about 5% per year. The majority of the city's residents are Jews.


title: Rishon LeZion

text: Rishon LeZion's main industries today are wine, construction, services and commerce. Factories and workshops are located in the old industrial zone, which has become a popular venue for pubs, dance clubs, and restaurants. Industry in the city is largely divided into two industrial centers: the old industrial zone in the north of the city and the new industrial zone in the west of the city.


title: Rishon LeZion

text: The three major malls in Rishon LeZion are "Rothschild Center" in the old downtown center, "Gold Mall" ("Kenyon HaZahav") in the New West district and the newly constructed "Azrieli Rishonim". Companies such as Coca-Cola, Gazit-Globe, Volvo and Fiat are expected to open in the Maayan Sorek area. As part of the city's 5-year plan to be completely water-independent, construction of a desalination plant is planned for Rishon, which will produce 3.7 million cubic meters of water per year. The city already hosts the large Shafdan recycling plant.


title: Rishon LeZion

text: Rishon LeZion has twenty-three elementary schools, nine middle schools, and twelve high schools. Rishon Lezion's College of Management has a student population of 10,000. Sixty percentage of twelve graders in the city qualify for a matriculation certificate.


title: Rishon LeZion

text: Rishon LeZion holds an annual wine festival. The Rishon LeZion Amphitheatre Live Park has hosted overseas artists such as Sting, Mariah Carey, Ozzy Osbourne, Metallica, Alanis Morissette, alt-J, Megadeth, Deep Purple, Avicii, Jason Derulo, Flo Rida, Wiz Khalifa and Sean Paul. The city has a municipal zoo, an amusement park (Superland), and a beach promenade. "Heychal HaTarbut" (Hall of Culture) is a venue for classical concerts, theatre performances and cultural events. It has a larger theatre for shows and two smaller ones for art workshops. The Israel Symphony Orchestra Rishon LeZion has participated in music festivals all over the world. It was awarded the ACUM Prize in 1991.


title: Rishon LeZion

text: A boardwalk (Tayelet Hatnei Pras Nobel) in honor of Jewish Nobel Prize winners was built, with cenotaphs of the laureates in Rishon LeZion.


title: Rishon LeZion

text: The city also has beautiful architecture and museums like the Rishon LeZion museum and the Yaakov Agam museum.


title: Rishon LeZion

text: Landmarks in Rishon LeZion include the history museum; the Carmel Winery; the administrative center of Edmond James de Rothschild, now a soldiers' memorial; the Great Synagogue; the Well; the old water tower; and Beit Sefer Haviv, the first Hebrew School. "Open Doors" is a holocaust memorial which is a 7-meter-high (23 ft) sculpture designed by Filipino artist Luis Lee Jr. It was erected in honor and thanks to President Manuel Quezon and the Filipinos who saved over 1,200 Jews from Nazi Germany.


title: Rishon LeZion

text: Rishon LeZion is located on the Israeli Mediterranean Coastal Plain and the northern Shephelah. The city sees the majority of its annual of precipitation between the months of October and March.


title: Rishon LeZion

text: Rishon LeZion can be divided into four main quarters: the old city, the eastern housing projects, the northern (old) industrial zone, and Western Rishon LeZion. There is also an industrial zone on the southern tip of the city, next to Gan Sorek.


title: Rishon LeZion

text: The old city of Rishon includes the original neighborhoods, some buildings dating back to Rishon's founding in 1881. This quarter is located in the city center, between and around Herzl and Jabotinsky Streets. It includes the following neighborhoods:


title: Rishon LeZion

text: Nahalat Yehuda (on the northernmost tip of Rishon); Neve Hillel; Bnot Hayil; Abramovich; Katzenelson; Remez (Giv'at Levinson), on the southwestern tip of old Rishon; Rishonim (Gan Nahum), to the east of Remez


title: Rishon LeZion

text: The Eastern Housing Projects ( "Shikunei HaMizrah") was Rishon's quick expansion to the east. It is dominated by the housing projects ("shikunim") there, in the "Shikunei HaMizrah" neighborhood itself. The eastern projects stopped developing when they reached the fences of the Tzrifin military base. When and if Tzrifin is sold to private contractors as planned, this quarter is expected to expand significantly with new lucrative housing projects. Other smaller neighborhoods include Revivim, Kidmat Rishon, Ne'urim, Rambam, Neve Hadarim, HaShomer, Kfar Arye, Mishor HaNof and Kiryat Simha.


title: Rishon LeZion

text: The industrial zones in Rishon LeZion are called "Mabat", an abbreviation for "Miskhar, Bilui VeTa'asiya" (Commerce, Pastime and Industry). The northern zone is the oldest and original industrial zone, once full of light industry and glass factories. Today, it is known for its prolific nightlife.


title: Rishon LeZion

text: West Rishon LeZion is the conglomeration of the new neighborhoods of the city, built in the 1980s and 90s. The west also has a higher land value because of its relative proximity to the Mediterranean Sea. It includes the entire city west of Tzahal Road. The quarter includes the new industrial zone (Western "Mabat"), and a number of residential neighborhoods: Neve Eliyahu (or Ramat Eliyahu), Neot Shikma, Neve Dekalim, Neve Hof (or Pueblo Español), Neve Yam, Kiryat Rishon, Kiryat Cramim, Kiryat Ganim, Neot Ashalim, Kiryat Hatanei Pras Nobel ("lit" Nobel Prize Laureates' Town)


title: Rishon LeZion

text: In handball, Hapoel Rishon LeZion and Maccabi Rishon LeZion dominate the handball league. Hapoel has won more than seven domestic championships and cups in a row, with stars like goalkeeper Vladimir Zaikman and field-players Idan Maimon and Dudi Balsar. Its biggest rival, Maccabi took the championship title from Hapoel in 2005/06. Handball is also a dominant sport in Rishon LeZion high schools. The "Amit Amal" high school handball team has won the world championship several times.


title: Rishon LeZion

text: In chess, the "Rishon LeZion Chess Club", founded in 1939, is one of the leading clubs in Israel, in senior, women and youth leagues. Israeli grandmasters such as Boris Alterman play for Rishon. World champion Garry Kasparov was a former member.


title: Rishon LeZion

text: Hapoel Rishon LeZion is the major football club, currently playing in the second tier, although the club played in the past in the top division, even as recently as 2011–12. The club also appeared in two cup finals, in 1946 and in 1996 and won the 2012–13 Toto Cup Leumit. Other active football teams are Moadon Sport Shikun HaMizrah (playing in Liga Alef), Hapoel Nahalat Yehuda (playing in Liga Bet), and Moadon Sport Rishon LeZion (playing in Liga Gimel). Other football clubs previously played in the city, such as Maccabi Rishon Lezion, which played at the top division during the 1940s and the two seasons after the Israeli Declaration of Independence, as well as smaller clubs which played in the lower tiers, such as Beitar Rishon LeZion, Hapoel Bnei Zion and Hapoel HaMegabesh Rishon LeZion.


title: Rishon LeZion

text: The main football stadium in Rishon LeZion is the 6,000-seats Haberfeld Stadium, which hosts matches of Hapoel Rishon LeZion. Other, smaller stadiums, are located in Shikun Hamizrah, in Nahlat Yehuda, and in the Superland complex.


title: Rishon LeZion

text: The Maccabi Rishon LeZion basketball team is a long-time member of Ligat HaAl, the top division. The team plays at Bet Maccabi Arena, which seats 2,500. Maccabi The team was a rival to Israel's top club and European champion, Maccabi Tel Aviv in the 1990s. It was surprise Ligat HaAl champion in the 2015-16 season.


title: Rishon LeZion

text: The Maccabi Rishon LeZion handball team is a long-time member of Ligat Ha'Al, the top division. Maccabi Rishon LeZion is the most time handball champion.


title: Rishon LeZion

text: The city also is home to the new 3,000-seats Athletics Municipal Stadium, which was built between 2001 and 2013, with the intention to host international athletics competitions.


title: Rishon LeZion

text: Rishon LeZion can be accessed by road from several major highways. Public transportation includes bus, train and share taxi.


title: Rishon LeZion

text: The Rishon LeZion HaRishonim Railway Station is located to the south of the city center, in the middle of HaRishonim Interchange, at the intersection of the new Highway 431 and the Rishon LeZion – Ness Ziona road. There are direct trains from the HaRishonim Railway Station to Tel Aviv, Lod, Bnei Brak, Petah Tikva, Rosh HaAyin, Hod HaSharon and Kfar Saba. All stations of Israel Railways can be accessed using the transfer stations at Tel Aviv and Lod.


title: Rishon LeZion

text: The Rishon LeZion Moshe Dayan Railway Station is in the western part of the city, situated on the new rail line from Tel Aviv to Ashdod via Moshe Dayan station and Yavne (West). There are future long-range plans for someday connecting the Rishonim station with Moshe Dayan station, while constructing a couple of additional railway stations in between them.


title: Rishon LeZion

text: Egged, Dan, Afikim, Metropoline, and Kavim. Rishon LeZion has an intracity bus network operated by Egged and Dan. Most lines are metropolitan, continuing to Bat Yam, Holon, Tel Aviv and Jaffa. The bus lines are augmented by share taxis operated by Moniyot HaIr.


title: Rishon LeZion

text: During the Gulf War in 1991, the mayor of Münster, Germany, made a surprise visit to Rishon LeZion. According to Haaretz, he felt he could not sit quietly at home while missiles were falling on his sister city. Throughout the war, he stayed at the home of Rishon LeZion mayor Meir Nitzan and accompanied him on visits to sites hit by missiles.


title: Rishon LeZion

text: In 2009 a memorial was erected in Rishon LeZion to the 10,000 German and Austrian Jews who found refuge in the Philippines during the Shoah.


title: Homer's Enemy

text: "Homer's Enemy" is the twenty-third episode of the eighth season of the American animated television series "The Simpsons". It was first broadcast on the Fox network in the United States on May 4, 1997. "Homer's Enemy" was directed by Jim Reardon and written by John Swartzwelder, based on an idea pitched by executive producer Bill Oakley.


title: Homer's Enemy

text: In the episode, Frank Grimes is hired as a new employee at the Springfield Nuclear Power Plant. Despite Homer's attempts to befriend him, Grimes is angered by Homer's laziness and incompetence. He decides to make Homer his enemy, and tries to expose his flaws through public humiliation. In the subplot, Bart buys a run-down factory for a dollar. The episode explores the comic possibilities of a realistic character with a strong work ethic hired for a job where he has to work alongside a man like Homer.


title: Homer's Enemy

text: Grimes was partially modeled after Michael Douglas's character in the film "Falling Down". Hank Azaria voiced Frank Grimes and based some of the character's mannerisms on actor William H. Macy. Frank Welker guest stars as the voice of the dog whom Burns wants as his executive vice president. In its original broadcast on the Fox network, "Homer's Enemy" acquired a 7.7 Nielsen rating. It was viewed in approximately 7.5 million homes, finishing the week ranked 56th. "Homer's Enemy" is considered to be one of the darkest episodes of "The Simpsons", and it split critical opinion. It is a favorite of several members of the production staff, including Bill Oakley, Josh Weinstein and Matt Groening, but it is one of the least favorites of Mike Reiss.


title: Homer's Enemy

text: After spending most of his life alone and working hard to make ends meet, Frank Grimes is hired at the Springfield Nuclear Power Plant after Mr. Burns learns of Grimes's hardship in a human-interest piece on the local news. Originally scouted to become the SNPP's Executive Vice-President, Grimes is later assigned to Sector 7G after another local news story moves Burns to hire a heroic dog to the EVP position instead. In 7G, Grimes must work alongside Homer Simpson and his two friends Lenny and Carl, quickly becoming aghast at Homer's laziness and incompetence, particularly after learning that he is the plant's health and safety inspector. When Grimes prevents Homer from accidentally drinking a flask of sulfuric acid by knocking it from his hands, Mr. Burns admonishes Grimes and reduces his pay, as the spilled acid destroyed a wall. Outraged, Grimes declares that he and Homer are now enemies. At Moe Szyslak's suggestion, Homer invites Grimes to his home for a lobster dinner, hoping to make amends. However, Grimes only grows more incensed by Homer's ability to live a comparatively more comfortable and successful life despite his sloth and ignorance, while Grimes has worked hard his whole life and has little to show for it. Denouncing Homer as a fraud, Grimes leaves in anger.


title: Homer's Enemy

text: The next day, Homer attempts to follow Marge's suggestion by acting as a model employee to impress Grimes, but his efforts fail as he is just as incompetent as before. Grimes rants to Lenny and Carl about Homer's obvious incompetence, but they insist that, despite his faults, Homer is a decent person. Instead of calming down, Grimes decides to prove Homer's lack of intelligence by tricking him into entering a children's contest to design a nuclear power plant in an attempt to humiliate him in front of everyone. Grimes's plan backfires when Homer's derivative model wins the contest and, when Homer's co-workers applaud rather than ridicule him, Grimes has a nervous breakdown and runs amok in the plant, mocking Homer's habits by imitating them. When Grimes gets carried away by grabbing hold of high-voltage wires without safety gloves, he is fatally electrocuted. At Grimes's funeral, Homer falls asleep and talks in his dream, making Reverend Lovejoy and the attendees laugh as Grimes's coffin is lowered into the earth.


title: Homer's Enemy

text: Meanwhile, after being dragged along to city hall by Marge for the purchase of a personalized license plate, Bart buys an abandoned factory for a dollar at a foreclosure auction. He and Milhouse spend their days wrecking the building until it collapses one night during Milhouse's watch, causing the rats in the building to swarm into Moe's Tavern.


title: Homer's Enemy

text: "Homer's Enemy" was written by John Swartzwelder, directed by Jim Reardon and executive produced by Bill Oakley and Josh Weinstein. One of the goals of Oakley and Weinstein was to create several episodes in each season that would "push the envelope conceptually." The idea for the episode was first conceived by Bill Oakley, who thought that Homer should have an enemy. The thought evolved into the concept of a "real world" co-worker who would either love or hate Homer. The writers chose the latter as they thought it would have funnier results.


title: Homer's Enemy

text: "Homer's Enemy" explores the comic possibilities of a realistic character with a strong work ethic placed alongside Homer in a work environment. In an essay for the book "Leaving Springfield", Robert Sloane describes the episode as "an incisive consideration of "The Simpsons"'s world. Although "The Simpsons" is known for its self-reflectivity, the show had never looked at (or critiqued) itself as directly as it does in ['Homer's Enemy']." In the episode, Homer is portrayed as an everyman and the embodiment of the American spirit; however, in some scenes his negative characteristics and silliness are prominently highlighted. By the close of the episode, Grimes, a hard-working and persevering "real American hero," is relegated to the role of antagonist; the viewer is intended to be pleased that Homer has emerged victorious. In an interview with "Simpsons" fan site NoHomers.net, Josh Weinstein said:


title: Homer's Enemy

text: The animators and character designers had a lot of discussion about what Frank Grimes should look like. He was originally designed as a "burly ex-marine guy with a crew cut", but would later be modeled after Michael Douglas in the movie "Falling Down" and director Jim Reardon's college roommate. Hank Azaria provided the voice of Frank Grimes, even though such a role would normally have been performed by a guest star. Among few others, the producers considered asking Nicolas Cage to play Grimes but decided Azaria was more suitable because the role involved a great deal of frustration and required extensive knowledge of the show. Azaria felt that the role should instead go to William H. Macy. According to Azaria, "I based the character on William Macy. I can't really copy him vocally, but I tried to get as close as I could and copy his rhythms and the way he has that sort of seething passion underneath that total calm exterior." The producers worked a lot with Azaria to help him perfect the role, and gave him more guidance than they normally would. Azaria felt that it was the role he worked hardest on, adding "I think it's the one we did the most takes on, the most emotional, it felt like the one I worked on the hardest from a performance point of view, in preparation and in execution."


title: Homer's Enemy

text: Josh Weinstein has expressed regret about killing off Grimes after only one episode, describing him as "such an amazing character." In an interview with "The Believer", producer George Meyer said, "Grimes's cardinal sin was that he shined a light on Springfield. He pointed out everything that was wrongheaded and idiotic about that world. And the people who do that tend to become martyrs. He said things that needed to be said, but once they were said, we needed to destroy that person. I'll admit, we took a certain sadistic glee in his downfall. He was such a righteous person, and that somehow made his demise more satisfying." Lisa has few speaking lines in the episode, due to Yeardley Smith getting the flu after recording all of her lines in "In Marge We Trust".


title: Homer's Enemy

text: The subplot, where Bart buys a factory, was added so that there would be some lighter scenes to split up the main plot. According to Weinstein, "We wanted to have a Bart or Lisa kids' story to contrast the heaviness and reality of Frank Grimes."


title: Homer's Enemy

text: In its original broadcast on the Fox network, "Homer's Enemy" acquired a 7.7 Nielsen rating. It was viewed in approximately 7.5 million homes, finishing the week ranked 56th. "The Simpsons" was the sixth highest rated show on Fox the week it was broadcast, behind "The X-Files", a broadcast of the film "The Mask", "Melrose Place", "King of the Hill" and "Beverly Hills, 90210". In Australia, the episode premiered on June 29, 1997, while in the UK it premiered on August 10, 1997.


title: Homer's Enemy

text: According to Josh Weinstein, when the episode was first broadcast, many fans felt it was too dark, lacked humor and that Homer was portrayed as overly bad-mannered. Weinstein considers this episode one of the most controversial of the seasons he ran, as it involves sharp observational humor that he thinks many fans "didn't get." Weinstein also talks about a "generation gap"—he believes the episode was originally panned by viewers, but has since become a favorite among fans who grew up with the show.


title: Homer's Enemy

text: Warren Martyn and Adrian Wood, authors of "I Can't Believe It's a Bigger and Better Updated Unofficial Simpsons Guide", described the episode as "one of the series' darkest episodes [that] ends on a real downer but is nevertheless also one of the wittiest and cleverest in ages." Similarly, comedian Rick Mercer called it a "great episode, and one of the darkest ever produced."


title: Homer's Enemy

text: Many critics have listed "Homer's Enemy" as one of the best episodes of the series, including John Orvted of "Vanity Fair", Entertainment.ie, Screen Rant, "The Guardian", and "Time". "IGN" ranked Frank Grimes as number 17 on a list of "The Top 25 "Simpsons" Peripheral characters", making him the least-frequently shown character to appear in that list.


title: Homer's Enemy

text: Several members of the staff have included the episode among their favorites. In a 2000 "Entertainment Weekly" article, Matt Groening ranked it as his sixth favorite "Simpsons" episode. It is also a personal favorite of Josh Weinstein, who cites the scene when Grimes visits the Simpson home as one of his favorite scenes, while "The Office" creator Ricky Gervais has called it "the most complete episode." In her autobiography "My Life as a 10-Year-Old Boy", Nancy Cartwright, the voice of Bart, praises Azaria's performance as Grimes, and uses it as an example of how "Accent, pitch, pacing, range and intention" can allow an actor to voice many characters. She writes,


title: Homer's Enemy

text: However, former "Simpsons" executive producer Mike Reiss listed "Homer's Enemy" as one of his two least favorite episodes, stating, "I just think the episode was in bad taste." Likewise, Jon Bonné of MSNBC used "Homer's Enemy" as an example of a bad episode of the eighth season and wrote "even now [in 2000], when subsequent episodes have debased Homer in new and innovative ways, the Grimes episode stands out as painful to watch."


title: Homer's Enemy

text: In August 2014, writing for "The Verge", Chris Plante listed "Homer's Enemy" as one of his favorite episodes of "The Simpsons", and Homer falling asleep and talking in his dream at Grimes's funeral as one of the funniest moments in the show, but he cited the latter as the moment the series jumped the shark, because of the impact it "has on the show's character [Homer], and through that character, the world."


title: Homer's Enemy

text: Despite his minimal screen time in the series overall, Frank Grimes has since been referenced many times in the show, often showing his tombstone, and occasionally mentioning him by name. In the season fourteen episode "The Great Louse Detective", it is revealed that he fathered a son named Frank Grimes Jr., who tries and fails to kill Homer. The footage of Grimes's death is also shown during the episode. He also appears in season twenty-six, as an angel with a halo in the opening sequence of "My Fare Lady", as Homer is exiting his work place. In the non-canon season twenty-eight episode "Treehouse of Horror XXVII", the ghost of Frank Grimes joins Sideshow Bob's army of the Simpsons' enemies.


title: Homer's Enemy

text: During the nuclear power plant design contest, one of the entrants is Ralph Wiggum, whose entry is rejected by Mr. Burns. When Ralph does not leave the stage, Chief Wiggum says "Ralphie, get off the stage, sweetheart." This line was later used as the chorus in the song "Ralph Wiggum" by the Bloodhound Gang.


title: Homer's Enemy

text: In February 2000, the cast of "The Simpsons" performed a live reading of the episode script at the US Comedy Arts Festival in Aspen, Colorado.


title: Tradesman

text: A tradesman, tradeswoman, or tradesperson is a skilled worker that specializes in a particular trade (occupation or field of work). Tradesmen usually have work experience, on-the-job training, and often formal vocational education in contrast to an apprentice, who is learning the trade.


title: Tradesman

text: As opposed to a craftsman or an artisan, the occupation of a tradesman is not necessarily restricted to manual work.


title: Tradesman

text: One study of Caversham, New Zealand at the turn of the century notes that a skilled trade was considered a trade that required an apprenticeship to entry. Skilled tradesmen worked either in traditional handicraft workshops or newer factories that emerged during the Industrial Revolution. Traditional handicraft roles included, for example: "sail-maker, candle-maker, cooper, japanner, lapidary and taxidermist, canister-maker, furrier, cap-maker, dobbin-maker, french-polisher, baker, miller, brewer, confectioner, watch-maker, tinsmith, glazier, maltster, wood-turner, saddler, shipwright, scale-maker, engraver and cutler."


title: Tradesman

text: Tradesmen are contrasted with laborers, agricultural workers, and professionals (those in the learned professions). Skilled tradesmen are distinguished:


title: Tradesman

text: There is no definitive list of modern skilled trades, as definitions vary, with some lists being broader than others.


title: Tradesman

text: A British study found that, after taking student loan repayments into account, a higher apprenticeship (at level 5 in the national qualifications frameworks) delivered higher lifetime median earnings than a degree from a university outside the Russell Group. Despite this, polling for the report found that apprenticeships have a lower perceived value than bachelor's degrees.


title: Tradesman

text: Data from the United States shows that, although vocational education is usually less financially lucrative in the long term than a bachelor's degree, it can still provide a respectable income at much less cost in time and money for training. Even ten years after graduation, there are many people with a certificate or associate degree who earn more money than those with a B.A.


title: Tradesman

text: The average taxable income for the top trades in Australia can be up to $100,000, while the average for all Australians is $85,800.


title: Wellcome Trust

text: The Wellcome Trust is a charitable foundation focused on health research based in London, in the United Kingdom. It was established in 1936 with legacies from the pharmaceutical magnate Henry Wellcome (founder of one of the predecessors of GlaxoSmithKline) to fund research to improve human and animal health. The aim of the Trust is to "support science to solve the urgent health challenges facing everyone." It had a financial endowment of £29.1 billion in 2020, making it the fourth wealthiest charitable foundation in the world. In 2012, the Wellcome Trust was described by the "Financial Times" as the United Kingdom's largest provider of non-governmental funding for scientific research, and one of the largest providers in the world. According to their annual report, the Wellcome Trust spent GBP £1.1Bn on charitable activities across their 2019/2020 financial year. According to the OECD, the Wellcome Trust's financing for 2019 development increased by 22% to US$327 million.


title: Wellcome Trust

text: The Wellcome Trust's operations are run from two buildings on Euston Road in London. The Wellcome Building, at 183 Euston Road, built in 1932 in Portland stone houses the Wellcome Collection and the adjoining glass and steel building at 215 Euston Road is the Gibbs Building, by Hopkins Architects, which opened in 2004 as the administrative headquarters of the Wellcome Trust. In 2019, the Wellcome Trust also opened an office in Berlin.


title: Wellcome Trust

text: The trust was established to administer the fortune of the American-born British pharmaceutical magnate Sir Henry Wellcome. Its income was derived from what was originally called Burroughs Wellcome, later renamed in the UK as the Wellcome Foundation Ltd. In 1986, the trust sold 25% of Wellcome plc stock to the public. Overseen by incoming Director of Finance Ian Macgregor, this marked the beginning of a period of financial growth that saw the trust's value increase by almost £14bn in 14 years, as their interests moved beyond the bounds of the pharmaceutical industry.


title: Wellcome Trust

text: In 1995, the trust divested itself of any interest in pharmaceuticals by selling all remaining stock to Glaxo plc, the company's historic British rival, creating GlaxoWellcome plc. In 2000, the Wellcome name disappeared from the drug business altogether when GlaxoWellcome merged with SmithKline Beecham, to form GlaxoSmithKline plc.


title: Wellcome Trust

text: Also known as SDDI, this five-year initiative started in October 2005 with the remit "to facilitate the development of drug-like small molecules that address unmet medical needs." SDDI was based in London and managed by Richard Davis. Through early 2010, SDDI had provided more than £80 million across 30 projects split between academic institutions and companies. To early 2010, all but one of the company recipients were either start-ups or spin-outs. In May 2010, an additional £110 million was added to the SDDI fund with the intent to extend the initiative for an additional 5 years.


title: Wellcome Trust

text: The Wellcome Trust announced the need for at least $8 billion of new funding for research, development, and supply of treatments related to COVID-19.


title: Wellcome Trust

text: In September 2019, Wellcome launched an initiative to reimagine research and improve the culture in which research is conducted. Current incentive structures and, as a result, culture and practices, prioritise publication outputs above all else. This is damaging people's wellbeing and undermining the quality of research itself.


title: Wellcome Trust

text: The Wellcome Trust plays an important role in encouraging publication of research in open access repositories such as Europe PubMed Central (EuropePMC). The Wellcome Trust believes that maximising the distribution of these papers – by providing free, online access – is the most effective way of ensuring that the research can be accessed, read and built upon. In turn, this will foster a richer research culture.


title: Wellcome Trust

text: In 2016, the Wellcome Trust partnered with the US National Institutes of Health (NIH) and the Howard Hughes Medical Institute to launch the Open Science Prize to "help develop services, tools and platforms that enable open content to be discovered, assessed and re-used in ways that will advance discovery and spark innovation."


title: Wellcome Trust

text: In 2016, Wellcome Trust announced that it would be launching Wellcome Open Research, an open access publication system running on the F1000 Research platform. Article processing charges will be covered directly by Wellcome Trust. Papers from the system are now indexed in PubMed Central.


title: Wellcome Trust

text: In the summer of 2015, the Wellcome Trust joined the Japanese government, 7 Japanese pharmaceutical and diagnostics companies, The Bill and Melinda Gates Foundation, and the United Nations Development Program as funding partner of the Global Health Innovative Technology Fund (GHIT), which funds scientific research and development for anti-infectives and diagnostics for diseases that primarily affect the developing world.


title: Wellcome Trust

text: In June 2007, the Wellcome Building reopened after refurbishment as a public venue, housing the Wellcome Collection, the Wellcome Trust Centre for the History of Medicine at University College London and the Wellcome Library. The aim of the Wellcome Collection is to enhance public understanding of medical science and history. The building contains gallery spaces, conference facilities, space for debates, drama and workshops, a café and a bookshop. The galleries show a small sample of works from Sir Henry Wellcome's collection, and host a programme of events and exhibitions. The Wellcome Collection and exhibitions are open to the public free of charge six days a week.


title: Wellcome Trust

text: The Wellcome Trust runs an annual photography prize which aims to explore "the human side of three urgent health challenges". Judges in 2021 include Dr Dixon Chabanda, Sir Jeremy Farrar, Dr Katerina Srahulkova and Azu Nwagbogu. Winners in each category receive a prize of £10,000.


title: Wellcome Trust

text: The Wellcome Trust sponsors an annual book prize, the Wellcome Book Prize, which "aims to excite public interest and encourage debate" around medicine and health.


title: Wellcome Trust

text: In June 2019, Wellcome released the results of the 2018 global survey on public attitudes toward science and health. Topics include trust of scientists, doctors, and nurses; religion and science, and vaccines, among others. It was Wellcome's first Global Monitor and was intended to "provide robust evidence on how public attitudes vary across different demographic groups and countries."


title: Wellcome Trust

text: In August 2014, the Wellcome Trust bought the Co-operative Group's farm business (renamed Farmcare) for £249 million. This comprised "15,997 hectares (39,533 acres) of freehold and third party owned land, 15 farms, including three pack houses, over 100 residential properties, and 27 commercial properties."


title: Wellcome Trust

text: It has been reported that the Wellcome Trust has billions of investments on companies which contribute to the problems the philanthropy wants to solve. Also in the context of the COVID-19 pandemic, it has been revealed that the trust has investments with pharmaceutical companies, which means it should gain financially from the pandemic.


title: Ocicat

text: The Ocicat is an all-domestic breed of cat which resembles a wild cat but has no recent wild DNA in its gene pool. The breed is unusual in that it is spotted like a wild cat but has the temperament of a domestic animal. It is named for its resemblance to the ocelot. The breed was established from the Siamese and Abyssinian. American Shorthair was also added to the original crosses due to an error in the Cat Fanciers' Association, Inc's recording of the breeds used. This mix of breeds created a healthy, large breed of cat completely different in type and appearance from the source breeds.


title: Ocicat

text: The first breeder of Ocicats was Virginia Daly, of Berkley, Michigan, who attempted to breed an Abyssinian-pointed Siamese in 1964. The first generation of kittens appeared Abyssinian, but the result in the second generation was not only the Abyssinian-pointed Siamese but also a spotted kitten, Tonga, nicknamed an "ocicat" by the breeder's daughter. Tonga was neutered and sold as a pet, but further breedings of his parents produced more spotted kittens, and became the basis of a separate Ocicat breeding program. Other breeders joined in and used the same recipe, Siamese to Abyssinian, and offspring to Siamese. In addition, due to an error by CFA in recording the cross that produced the Ocicat, the American Shorthair was introduced to the Ocicat giving the breed larger boning and adding silver to the 6 colors. The Ocicat was initially accepted for registration in The Cat Fanciers' Association, Inc., and was moved into Championship for showing in 1987. Other registries followed. Today the Ocicat is found all around the world, popular for its all-domestic temperament but wild appearance. The Ocicat was named by Virginia's daughter, Virginia E. Daly.


title: Ocicat

text: The ideal Ocicat has almond shaped eyes, a large, strong body, muscular legs, and powerful, oval shaped paws. The head is a wedge shape, that is, longer than wide. Their ears are tilted at a 45 degree angle. One of the most striking things about this breed is the large, thumbprint-shaped contrasting spots. The breed's large, well-muscled body gives an impression of power and strength. Females weigh from 6 to 9 pounds on average, and males from 9 to 15.


title: Ocicat

text: Twelve variations in color are approved by most registries, including The Cat Fanciers' Association, Inc. The standard for the Ocicat breed is tawny (genetic black), chocolate and cinnamon, their dilutes, blue, lavender and fawn, black silver (or ebony silver), chocolate silver, cinnamon silver, blue silver, lavender silver and fawn silver.


title: Ocicat

text: Ocicats have inherited personality traits from both Siamese and Abyssinians, two breeds considered to be domesticated for many thousands of years. They will often greet your guests, and are friendly and sociable. They are ideal pets for most households, generally tolerating gentle children and other pets.


title: Ocicat

text: Their temperament is often described as that of a "dog in a cat's body". Most can be trained to fetch, walk on a leash and harness, come when called, speak, sit, lie down on command and other canine-style tricks. Some even take readily to water. Most are especially agile and are motivated by play with toys. Given these attributes, the Ocicat requires more attention from its owners than most breeds. They do get along well with other animals and people, however, and appreciate an animal companion to keep them company if left alone for any length of time. The uniqueness of this breed lies in the fact that they can behave like the original ocelot. Ocicats show habits of wild cats such as hunting (but not in distant places, since the ocicats are unlikely to go far from home if the largest fence is installed next to the house area), spying so that nothing happens to the kittens, and recognizing small outlandish animals as prey. But they are not devoid of domestic habits.


title: Brian Orser

text: Brian Ernest Orser, (born 18 December 1961) is a Canadian former competitive and professional figure skater and coach to Olympic champions. He is the 1984 and 1988 Olympic silver medallist, 1987 World champion and eight-time (1981–88) Canadian national champion. At the 1988 Winter Olympics, the rivalry between Orser and American figure skater Brian Boitano, who were the two favorites to win the gold medal, captured media attention and was described as the "Battle of the Brians".


title: Brian Orser

text: Orser turned professional in 1988 and skated with Stars on Ice for almost 20 years. As a coach, he has led both Yuna Kim (2010) and Yuzuru Hanyu (2014, 2018) to Olympic titles. He also coached Javier Fernández to Olympic bronze (2018) and the 2015 and 2016 World titles. He is a Skating Consultant at the Toronto Cricket Skating and Curling Club.


title: Brian Orser

text: Brian Orser was born in Belleville, Ontario. He grew up in Penetanguishene. He is the youngest of five children.


title: Brian Orser

text: Orser won his first national title on the novice level in 1977. The following season, he went to Junior Worlds and placed 4th, behind eventual rival Brian Boitano. He added a second national title, this time at the junior level, to his resume in 1979.


title: Brian Orser

text: In 1980, he moved up to the senior level. He won the bronze medal at his first senior international, the Vienna Cup, and then placed 4th at the Canadian Figure Skating Championships. That was the last time he would place off the podium at the national level.


title: Brian Orser

text: In the 1980–1981 post-Olympic season, Orser began making his mark on the skating world. He won the silver at the Nebelhorn Trophy, placed 6th at Skate Canada, and then won his first of eight National titles. In his debut at Worlds, he placed 6th. The next season, he won his first medal at Skate Canada and moved up to 4th at Worlds. He won his first World medal in 1983, a bronze, positioning him well for the 1983–1984 Olympic season.


title: Brian Orser

text: Orser became the second man to land the triple Axel when he performed it in winning his Canadian junior title in 1979, at a time when few senior skaters were even attempting it. Over the next few years, Orser performed the jump more frequently and more consistently than any other skater of the time. Orser became the first man to land the triple Axel at the Olympics when he landed it in his free skate at the 1984 Winter Olympics. He won the silver medal behind Scott Hamilton, and then won the silver at 1984 Worlds, again behind Hamilton. Only Orser's low placements in the compulsory figures prevented him from winning both titles.


title: Brian Orser

text: In the 1984–1985 season, after Hamilton's retirement, Orser was seemingly poised to become the dominant champion. However, he had an imperfect worlds, and placed second to Alexander Fadeev, who also had the triple Axel in his repertoire. Orser resolved to begin including two Axels, not just one, in his free skate, in order to give himself an advantage over Fadeev. He finally won Worlds in 1987. At that competition he became the first skater at the World Championships to land two triple Axels in the free skate and three in the same competition.


title: Brian Orser

text: Going into the 1988 Olympics, Orser worked with a sports psychologist on visual imagery. He and Brian Boitano were thrust into the Battle of the Brians, each being the other's main rival. Orser was undefeated in the 1986–1987 season and had not lost a competition since losing to Boitano at the 1986 Worlds. At the Olympics, Orser served as the flag-bearer for Canada during the opening ceremonies. He placed 3rd in compulsory figures segment of the competition, 1st in the short program, and second in the free skating, winning the silver medal overall. Brian Boitano won the gold medal, defeating Orser by 0.10 points.


title: Brian Orser

text: He won the silver again at Worlds in 1988, after winning the free skate. Orser turned professional following that season. He had not placed off a podium at any competition since 1982. During his competitive career, he trained at the Mariposa School of Skating, originally located in Orillia, Ontario and was moved to Barrie, Ontario in 1988. An arena in Orillia was renamed for Orser in 1984.


title: Brian Orser

text: Orser began touring with Stars on Ice in 1988, soon after ending his competitive career. He would go on to appear with them on and off for nearly 20 years, skating his last with the show in 2007.


title: Brian Orser

text: Orser starred in the 1990 German skating dance film "Carmen on Ice", alongside his archrival Brian Boitano and Katarina Witt. The film told the story of "Carmen" wordlessly through ice skating; Orser played the part of Escamillo.


title: Brian Orser

text: Orser performed in many ice shows and was known in the show business as one of the few people who could perform a backflip. Unfortunately, in 2007, he suffered from a broken wrist which occurred while stepping backward off the ice. Since then he has decided not to continue doing backflips and has greatly decreased his participation in ice shows.


title: Brian Orser

text: Orser, along with his two co-stars, won an Emmy Award for his performance in "Carmen on Ice" after it appeared on HBO.


title: Brian Orser

text: Orser is openly gay. He was forced to reveal his sexuality in November 1998, when he lost a legal battle to prevent public disclosure when his former partner sued him for palimony. Orser initially feared the revelation of being gay would ruin his career, but he has since embraced support from other skaters and the public. Since 2008, he has been in a relationship with Rajesh Tiwari, a director of The Brian Orser Foundation. Harvey Brownstone, Canada's first openly gay judge, officiated at their wedding ceremony.


title: Self-defeating personality disorder

text: Self-defeating personality disorder (also known as masochistic personality disorder) was a proposed personality disorder. As a descriptor for "Other personality disorder" it was mentioned in the DSM-III in 1980. It was discussed in an appendix of the revised third edition of the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-III-R) in 1987, but was never formally admitted into the manual. Because of its significant overlap with other personality disorders (borderline, avoidant and dependent) the distinction was not seen as clinically valuable. It was entirely excluded from the DSM-IV. Since the DSM-5, the diagnoses other specified personality disorder and unspecified personality disorder have mostly replaced its use.


title: Self-defeating personality disorder

text: Historically, masochism has been associated with feminine submissiveness. This disorder became politically controversial when associated with domestic violence which was considered to be mostly caused by males. However a number of studies suggest that the disorder is common. In spite of its exclusion from DSM-IV in 1994, it continues to enjoy widespread currency amongst clinicians as a construct that explains a great many facets of human behaviour.


title: Self-defeating personality disorder

text: Sexual masochism that "causes clinically significant distress or impairment in social, occupational, or other important areas of functioning" is still in DSM-IV.


title: Self-defeating personality disorder

text: Theodore Millon has proposed four subtypes of masochist. Any individual masochist may fit into none, one or more of the following subtypes:


title: Mick Ralphs

text: Michael Geoffrey Ralphs (born 31 March 1944, Herefordshire) is an English musician, vocalist and songwriter, who was a founding member of rock bands Mott the Hoople and Bad Company.


title: Mick Ralphs

text: Ralphs began his career as a teenager, playing with blues-rock band the Buddies. He released a single with that group in 1964 before joining the Mod Doc Thomas Group in 1966. After an eponymous Italian album debut, the band changed its name twice, first to Silence in 1968 and then, in 1969, to Mott the Hoople. Ralphs remained with Mott until 1973.


title: Mick Ralphs

text: In 1973, he founded Bad Company along with vocalist Paul Rodgers from Free. The band's debut album in 1974 included the Ralphs'-penned hit "Can't Get Enough", for which Ralphs tuned his guitar in the open-C tuning C-G-C-G-C-E, stating, "It never really sounds right in standard tuning. It needs the open C to have that ring." The debut album reached number one in the United States. Ralphs continued to record and tour with Bad Company until the original band folded in 1982.


title: Mick Ralphs

text: In 1984 he toured with Pink Floyd guitarist David Gilmour on Gilmour's About Face tour, although he did not play on the album. In 1985, he released a solo album, "Take This", which included Free's and Bad Company's drummer Simon Kirke. He teamed up with future Bad Company guitarist Dave Colwell for a limited four-run live support of the album, which also featured drummer Chris Slade of Manfred Mann's Earth Band and keyboard player Lindsay Bridgewater, who performed with Ozzy Osbourne. He did one performance with a band called Cold Turkey.


title: Mick Ralphs

text: Bad Company reformed with different line-ups between 1986 and 1998. But after a reunion tour with the original foursome in 1999, Ralphs announced that he was giving up touring, something he was never comfortable with in either band, since he has an extreme fear of flying.


title: Mick Ralphs

text: Ralphs second solo album "It's All Good", an instrumental, came out in 2001. Two years later his "That's Life – Can't Get Enough" album was released, including a demo version of "Can't Get Enough".


title: Mick Ralphs

text: In 2004, he once again teamed up with former Mott colleague Ian Hunter, playing second lead guitar (along with Andy York) on Hunter's UK tour. Ralphs performed at Hunter's 2005 concert at the London Astoria, with Ralphs performing a guitar solo to "All the Way from Memphis".


title: Mick Ralphs

text: On 2 July 2008, it was announced that the original line-up of Bad Company (minus Boz Burrell who died in September 2006) would do a one-off gig at the Hard Rock Hotel and Casino in Hollywood, Florida on 8 August 2008. According to Rodgers, they did this gig to "protect the legacy they have built and cement the rights to the trademark Bad Company for touring".


title: Mick Ralphs

text: Mott the Hoople, including Ralphs, reunited for two shows at the Blake Theatre in Monmouth close to Rockfield Studios where they rehearsed before playing five concerts at the Hammersmith Apollo in London, during September and October 2009. All five of the original members participated in the reunion with Martin Chambers assisting on drums.


title: Mick Ralphs

text: In 2011, Ralphs formed The Mick Ralphs Blues Band with musicians he met while guesting at a jam session at the Nag's Head pub in High Wycombe: Stuart Son Maxwell, harmonica/vocals; Jim Maving, guitar; Sam Kelly, drums; Dickey Baldwin, bass. The band's website stated that Ralphs sought to explore his blues and soul roots, playing covers of classic blues and R&B songs. The band made its debut as Mick Ralphs and Co at Jagz Club in Ascot, Berkshire in June 2011, changing the name to the Mick Ralphs Blues Band soon afterwards. More dates were announced for late 2011 and early 2012.


title: Mick Ralphs

text: In 2013 and 2014, Bad Company and Lynyrd Skynyrd jointly toured throughout the United States and Canada, initially commemorating the 40th anniversary of Skynyrd's first album release and Bad Company's formation.


title: Mick Ralphs

text: In 2016, Bad Company announced a US tour with Joe Walsh. Ralphs initially announced that he would not be participating in this tour and that Rich Robinson of the Black Crowes would be standing in for him. In June 2016, the group announced a UK arena tour with special guests Richie Sambora and Orianthi culminating in a show at London's O2 Arena on 29 October. Ralphs rejoined the band for the duration of the tour. Following the band's concluding performance in London, it was reported that Ralphs had been hospitalized, having suffered a stroke. He has not returned to the band since with his lead guitar parts being played by second guitarist, Howard Leese and keyboard parts being played by Rogers.


title: Flight number

text: In the aviation industry, a flight number or flight designator is a code for an airline service consisting of two-character airline designator and a 1 to 4 digit number. For example, "BA 98" is a British Airways service from Toronto-Pearson to London-Heathrow. A service is called "direct" if it is covered by a single flight number, regardless of the number of stops or equipment changes. For example, "WN 417" flies from Jacksonville to Baltimore to Oakland to Los Angeles on Southwest Airlines. A given flight segment may have multiple flight numbers on different airlines under a code-sharing agreement. Strictly speaking, the flight number is just the numerical part, but it is commonly used for the entire flight designator.


title: Flight number

text: The flight designator of the operating carrier of a commercial flight is used as a call sign. This is distinct from the aircraft's registration number, which identifies a specific airplane.


title: Flight number

text: A number of conventions have been developed for defining flight numbers, although these vary widely from airline to airline, and are increasingly being modified. Eastbound and northbound flights are traditionally assigned even numbers, while westbound and southbound flights have odd numbers. Other airlines will use an odd number for an outbound flight and use the next even number for the reverse inbound flight. For destinations served by multiple flights per day, numbers tend to increase during the day. Hence, a flight from point A to point B might be flight 101 and the return flight from B to A would be 102, while the next pair of flights on the same route would usually be assigned codes 103 and 104.


title: Flight number

text: Flight numbers of less than three digits are often assigned to long-haul or otherwise premium flights. For example, flight number 1 is often used for an airline's "flagship" service (see below for a 'List of flight number 1 by airlines'). However, for airlines in Mainland China, one-digit and two-digit numbers are only reserved for administrative charters. Furthermore, Cathay Pacific assigns flight numbers which are less than 100 for cargo flights.


title: Flight number

text: Four-digit numbers in the range 3000 to 5999 typically represent regional affiliate flights, while numbers larger than 6000 are generally codeshare numbers for flights operated by different airlines or even railways.


title: Flight number

text: Likewise, flight numbers larger than 9000 usually refer to ferry flights; these carry no passengers and are used to relocate aircraft to or from a maintenance base, or from one air travel market to another in order to start new commercial flights. Flight numbers starting with 8 are often used for charter flights, but it always depends on the commercial carrier's choice.


title: Flight number

text: In a codeshare, airlines share their aircraft with others, resulting in the flight having more than one flight number on the same sector, and either the same or different flight numbers on joined sectors.


title: Flight number

text: As a hypothetical example, flight QQ1234 may fly from airport AAA to BBB to CCC. The AAA-BBB segment may be serviced by airline QQ, and the BBB-CCC segment by airline RR, on a different aircraft. The same flight may also be sold as RR3210, and by a third airline SS as SS2345. Also, the individual flight legs may have multiple flight numbers: AAA-BBB may be QQ12, RR23, and SS45.


title: Flight number

text: For example, Alaska Airlines flight AS61 flies from Juneau (JNU) to Yakutat (YAK) to Cordova (CDV) to Anchorage (ANC). A ticket for the Yakutat to Anchorage segment is specified as AS61 YAK-ANC. It is even possible for a given flight number to cover a sequence beginning and ending at the same airport.


title: Flight number

text: Most flights are non-stop from A to B, and few are from A to B then to C (both A-B and B-C have flight number 1). Aircraft type may change due to operation need.


title: Flight number

text: A notable former flight number 1 was British Airways flight BA1, operated by the Concorde between London Heathrow and New York's John F. Kennedy airport. After the retirement of Concorde in 2003 the flight number was retired with it, however in 2009 it was given to the all business class A318 flight between London City Airport and New York JFK via Shannon in Ireland. This route ceased operation in 2020 due to the COVID-19 pandemic, and British Airways has since announced it will not be restarting the service.


title: Flight number

text: Flight numbers are often taken out of use after a crash or a serious incident. For example, following the crash of Malaysia Airlines Flight 370, the airline changed the flight number for subsequent flights following the same route to MAH 318. Also, American Airlines Flight 77, which regularly flew from Dulles International Airport in Washington, DC, to Los Angeles International Airport, was changed to Flight 149 after it crashed into the Pentagon during the September 11 attacks. After the crash of Air France Flight 447, a regular scheduled flight from Rio de Janeiro to Paris, was changed to Air France Flight 443. On the other hand, other considerations may lead an airline not to change a flight number; for instance, the aforementioned "flagship" American Airlines Flight 1 retains its designation despite a major accident in 1962 and two other accidents in 1941 and 1936. There are at least four instances of the same flight numbers that have suffered two serious accidents: Flight 253 of Linea Aeropostal Venezolana (both in 1956, the first in June, and the second in November), Flight 869 of United Arab Airlines (the first in 1962 and the second in 1963), Flight 800 of TWA (the first in 1964 and the second in 1996), and Flight 383 of American Airlines (the first in 1965 and the second in 2016). As of October 2019 the most recent flight number change due to an accident was from Aeroflot Flight 1492 to Aeroflot Flight 1316. In 2016 after the crash of flight 804, Egyptair changed it to 802 from Paris to Cairo. In 1998, after the crash of flight 111, Swissair changed it to 139 from New York To Geneva. In 1997, after the crash of flight 801 from Seoul to Guam, Korean Airlines changed it to number 805.


title: Flight number

text: Airline mega mergers, in markets such as the United States, have made it necessary to break conventional flight numbering schemes. Organizations such as IATA, ICAO, ARC, as well as CRS systems and the FAA's ATC systems limit flight numbers to four digits (0001 to 9999). The pool of available flight numbers has been outstripped by demand for them by emergent mega-carriers. As such, some carriers use the same flight number for back-and-forth flights (e.g., DCA-PBI-DCA), or in other cases carriers have assigned a single flight number to a multi-leg flight (e.g., ICT-DAL-HOU-MDW-OMA-DEN-ABQ-LAS-BDL).


title: Flight number

text: Although 'flight number' is the term used colloquially, the official term as defined in the Standard Schedules Information Manual (SSIM) published annually by the International Air Transport Association (IATA) Schedules Information Standards Committee (SISC), is flight designator. Officially the term 'flight number' refers to the numeric part (up to four digits) of a flight code. For example, in the flight codes BA2490 and BA2491A, "2490" and "2491" are flight numbers. Even within the airline and airport industry, it is common to use the colloquial term rather than the official term.


title: Flight number

text: Flight numbers are also sometimes used for spacecraft, though a flight number for an expendable rocket (say, Ariane 5 Flight 501) might more reasonably be called the serial number of the vehicle used, since an expendable rocket can only be launched once. Space Shuttle missions used numbers with the STS prefix, for example, STS-93. SpaceX uses sequential numbers for flights of reused boosters. As an example, Crew-2 used booster B1061.2 (the second flight of booster B1061).


title: Lillian Gordy Carter

text: Bessie Lillian Carter (née Gordy; August 15, 1898 – October 30, 1983) was the mother of the 39th president of the United States Jimmy Carter. She was also known for her contributions to nursing in her home state of Georgia and as a Peace Corps volunteer in India as well as writing two books during the Carter presidency.


title: Lillian Gordy Carter

text: Carter was born Bessie Lillian Gordy on August 15, 1898, in Richland, Georgia, to James Jackson Gordy (1863–1948) and Mary Ida Nicholson Gordy (1871–1951). She was the niece of Berry Gordy I, who was the paternal half-brother of James Jackson Gordy and the grandfather of Motown Records founder Berry Gordy. She volunteered to serve as a nurse with the U.S. Army in 1917 but the program was cancelled. Instead, she worked for the US Post Office at Richland before moving to Plains, Georgia in 1920 where she was accepted as a trainee at the Wise Sanitarium before completing her nursing degree at the Grady Memorial Hospital School of Nursing in Atlanta, Georgia in 1923. Lillian's family initially disapproved of her choice of a career in nursing, but she continued her training and became very successful, earning the respect of both the black and white communities. "Miss Lillian", as she was often known, allowed black people to enter her home through the front door, rather than through the back door as was the social norm, and would often have them in her living room for casual conversation just as she would a white neighbor. These conversations would even continue after her husband Earl was to arrive home expecting the guests to depart.


title: Lillian Gordy Carter

text: Lillian Carter said that the strongest influence on her liberal views was her father. James Jackson Gordy, operated a Post Office in Lillian's hometown of Richland and was always cordial and often dined with the black workers. It was very unusual in the early 20th century but Lillian decided that she would follow her father's example.


title: Lillian Gordy Carter

text: She met businessman James Earl Carter and married him immediately after her graduation. The couple had four children: Jimmy (born 1924), Gloria (1926–1990), Ruth (1929–1983), and Billy (1937–1988). While she theoretically retired from nursing in 1925, in reality she worked as what was then called a nurse practitioner both for the hundreds of employees back in her husband's businesses and for members of the Plains community. While a religious woman, Carter was not a regular attender of church services. After some sisters at the local church organized a mission trip to Africa, Carter became upset saying that there was plenty to be done in the US before traveling to another country. She coordinated her own Bible study at home on Sunday mornings while the rest of the family attended church.


title: Lillian Gordy Carter

text: After the death of her husband from pancreatic cancer, Lillian Carter left for Auburn University where she assumed the role of housemother of Kappa Alpha Order, a fraternity of 100 members at the time. She served in that role from 1956 to 1962. A year after completing her service at Auburn, Carter managed a nursing home in Blakely, Georgia.


title: Lillian Gordy Carter

text: Carter later became a social activist, working for desegregation and providing medical care to African-Americans in Plains, Georgia.


title: Lillian Gordy Carter

text: In 1966, at the age of 68, Carter applied for the Peace Corps. After completing a psychiatric evaluation, she received three months of training and was sent to India where she worked at the Godrej Colony from Mumbai. She worked there for 21 months; she aided patients with leprosy. Emory University established the Lillian Carter Center for International Nursing in honor of her work in India. The Atlanta Regional Office of the Peace Corps has named an award in her honor for volunteers over 50 who make the biggest contribution.


title: Lillian Gordy Carter

text: When Jimmy Carter decided to run for president, his mother was one of the first people he told. He was initially regarded as a dark horse candidate for the Democratic Party nomination.


title: Lillian Gordy Carter

text: Lillian Carter was well known as "Miss Lillian" and she published two books during his presidency: "Miss Lillian and Friends" and "Away from Home: Letters to my Family", both published in 1977. The latter book was a collection of letters to her family sent when she was in India for the Peace Corps.


title: Lillian Gordy Carter

text: "Miss Lillian" was a favorite of the press for her Southern charm and down-to-earth manner. For reporters and interrogators alike, she always had a warm, sassy response for every question. One biographer recalls a story about an encounter between Carter and a reporter from New York who flew to Plains to meet her during her son's 1976 campaign to become the U.S. president:


title: Lillian Gordy Carter

text: In 1977, Lillian Carter appeared in a cameo as herself in the made-for-TV movie "Lucy Calls the President" starring Lucille Ball.


title: Lillian Gordy Carter

text: When son Billy's beer business had its ribbon-cutting ceremony, a friend questioned Carter on whether or not she would attend. She remarked: "I attended Jimmy's inauguration didn't I?"


title: Lillian Gordy Carter

text: Together with vice president Walter Mondale, Lillian Carter was head of the U.S. delegation to the funeral of Yugoslav president Josip Broz Tito.


title: Lillian Gordy Carter

text: Shortly after her eldest son left office in January 1981, Carter was diagnosed with breast cancer. While her cancer was in remission in April 1983, her younger daughter, Ruth Carter Stapleton, was diagnosed with pancreatic cancer and died on September 26, 1983, aged 54. Carter herself succumbed to breast cancer that metastasized to the bone a month later on October 30, 1983, at age 85 in Americus, Georgia. Her three surviving children were by her side at her death. Carter was buried in a simple six-minute ceremony at Lebanon Church Cemetery, on November 1, 1983, next to her husband, who died 30 years before her.


title: Lillian Gordy Carter

text: In addition to her husband and daughter, two more of her children, Gloria Carter Spann, and Billy Carter, also died from pancreatic cancer. The former president was diagnosed with melanoma in 2015, at the age of 90. He survived the cancer and stopped treatments in March 2016. In 2010, he had a severe stomach ache which was mistaken as pancreatic cancer. He has been a fundraiser and booster for research into a cure for the disease.


title: Lillian Gordy Carter

text: In 2001, a major nursing center was dedicated in her honor in Plains by Jimmy Carter in recognition of her first years of service to the community as a nurse. In 2011 she was inducted into the Georgia Women of Achievement.


title: Fetal hemoglobin

text: Fetal hemoglobin, or foetal haemoglobin (also hemoglobin F, HbF, or αγ) is the main oxygen carrier protein in the human fetus. Hemoglobin F is found in fetal red blood cells, and is involved in transporting oxygen from the mother's bloodstream to organs and tissues in the fetus. It is produced at around 6 weeks of pregnancy and the levels remain high after birth until the baby is roughly 2–4 months old. Hemoglobin F has a different composition from the adult forms of hemoglobin, which allows it to bind (or attach to) oxygen more strongly. This way, the developing fetus is able to retrieve oxygen from the mother's bloodstream, which occurs through the placenta found in the mother's uterus.


title: Fetal hemoglobin

text: In the newborn, levels of hemoglobin F gradually decrease and reach adult levels (less than 1% of total hemoglobin) usually within the first year, as adult forms of hemoglobin begin to be produced. Diseases such as beta thalassemias, which affect components of the adult hemoglobin, can delay this process, and cause hemoglobin F levels to be higher than normal. In sickle cell anemia, increasing the production of hemoglobin F has been used as a treatment to relieve some of the symptoms.


title: Fetal hemoglobin

text: Hemoglobin F, like adult hemoglobin (hemoglobin A and hemoglobin A2), has four subunits or chains. Each subunit contains a heme group with an iron element which is key in allowing the binding and unbinding of oxygen. As such, hemoglobin F can adopt two states: oxyhemoglobin (bound to oxygen) and deoxyhemoglobin (without oxygen). As hemoglobin F has 4 heme groups, it can bind to up to four oxygen molecules. It is composed of two α (alpha) subunits and two γ (gamma) subunits, whereas hemoglobin A (97% of total hemoglobin in adults) is composed of two α and two β (beta) subunits.


title: Fetal hemoglobin

text: In humans, the α subunit is encoded on chromosome 16 and the γ subunit is encoded on chromosome 11. There are two very similar genes that code for the α subunit, HBA1 and HBA2. The protein that they produce is identical, but they differ in gene regulatory regions that determine when or how much of the protein is produced. This leads to HBA1 and HBA2 each contributing with 40% and 60%, respectively, of the total of α subunits produced. As a consequence, mutations on the HBA2 gene are expected to have a stronger effect than mutations on the HBA1 gene.


title: Fetal hemoglobin

text: There are also two similar copies of the gene coding for the γ subunit, HBG1 and HBG2, but the protein produced is slightly different, just in one protein unit: HBG1 codes for the protein form with an alanine at position 136, whereas HBG2 codes for a glycine (see ).


title: Fetal hemoglobin

text: BCL11A and ZBTB7A are major repressor proteins of hemoglobin F production, by binding to the gene coding for the γ subunit at their promoter region. This happens naturally as the newborn baby starts to switch from producing hemoglobin F to producing hemoglobin A.


title: Fetal hemoglobin

text: Some genetic diseases can take place due to mutations to genes coding for components of hemoglobin F. Mutations to HBA1 and HBA2 genes can cause alpha-thalassemia and mutations to the promoter regions of HBG1 and HBG2 can cause hemoglobin F to still be produced after the switch to hemoglobin A should have occurred, which is called hereditary persistence of fetal hemoglobin.


title: Fetal hemoglobin

text: During the first 3 months of pregnancy, the main form of hemoglobin in the embryo/fetus is embryonic hemoglobin, which has 3 variants depending on the types of subunits it contains. The production of hemoglobin F starts from week 6, but it's only from 3 months onwards that it becomes the main type found in fetal red blood cells.


title: Fetal hemoglobin

text: The switch to produce adult forms of hemoglobin (essentially hemoglobin A) starts at around 40 weeks of gestation, which is close to the expected time of birth. At birth, hemoglobin F accounts for 50-95% of the infant's hemoglobin and at around 6 months after birth, hemoglobin A becomes the predominant type. By the time the baby is one year old, the proportions of different types of hemoglobin are expected to approximate the adult levels, with hemoglobin F reduced to very low levels. The small proportion of red blood cells containing hemoglobin F are called F-cells, which also contain other types of hemoglobin.


title: Fetal hemoglobin

text: In healthy adults, the composition of hemoglobin is hemoglobin A (~97%), hemoglobin A2 (2.2 - 3.5%) and hemoglobin F (<1%).


title: Fetal hemoglobin

text: Certain genetic abnormalities can cause the switch to adult hemoglobin synthesis to fail, resulting in a condition known as hereditary persistence of fetal hemoglobin.


title: Fetal hemoglobin

text: The four hemes, which are the oxygen-binding parts of hemoglobin, are similar between hemoglobin F and other types of hemoglobin, including hemoglobin A. Thus, the key feature that allows hemoglobin F to bind more strongly to oxygen is by having γ subunits (instead of β, for example). In fact, some naturally existing molecules in our body can bind to hemoglobin and change its binding affinity for oxygen. One of the molecules is 2,3-bisphosphoglycerate (2,3-BPG) and it enhances hemoglobin's ability to release oxygen. 2,3-BPG interacts much more with hemoglobin A than hemoglobin F. This is because the adult β subunit has more positive charges than the fetal γ subunit, which attract the negative charges from 2,3-BPG. Due to the preference of 2,3-BPG for hemoglobin A, hemoglobin F binds to oxygen with more affinity, in average.


title: Fetal hemoglobin

text: Hemoglobin Barts is an abnormal form of hemoglobin produced in hemoglobin Barts syndrome or alpha-thalassemia major, the most severe form of alpha-thalassemia. Alpha-thalassemia is a genetic blood disorder and one of the most common hemoglobin-related diseases, affecting the production of α subunits from hemoglobin. Depending on how many genes coding for the α subunit are impacted (between one and four), patients with this disease can have reduced to no production of the α subunit of the hemoglobin. As a consequence, less hemoglobin is available and this affects oxygen supply to the tissues.


title: Fetal hemoglobin

text: Hemoglobin Barts syndrome manifests when all four genes coding for α subunit are deleted. This is often fatal for the fetus carrying the disorder, as in the absence of α subunits, a form of hemoglobin with four γ subunits, hemoglobin Barts, is produced. This form of hemoglobin isn't fit for oxygen exchange precisely due to its very high affinity for oxygen. While hemoglobin Barts is very efficient at binding oxygen, it doesn't release oxygen to the organs and tissues. The disease is fatal for the fetus or newborn unless early diagnosis and intervention is carried out during pregnancy, and the child will be dependent on lifelong blood transfusions.


title: Fetal hemoglobin

text: To quantify how strongly a certain type of hemoglobin binds to oxygen (or its affinity for oxygen), a parameter called P50 is often used. In a given situation, P50 can be understood as the partial pressure of oxygen at which Hb is 50% saturated. For example, Hemoglobin F has a lower P50 than hemoglobin A. This means that if we have the same amount of hemoglobin F and hemoglobin A in the blood and add oxygen to it, half of hemoglobin F will bind to oxygen before half of hemoglobin A manages to do so. Therefore, a lower P50 means stronger binding or higher affinity for oxygen.


title: Fetal hemoglobin

text: For reference, the P50 of fetal hemoglobin is roughly 19 mmHg (a measure of pressure), whereas adult hemoglobin is approximately 26.8 mmHg (see Blood gas tension).


title: Fetal hemoglobin

text: During pregnancy, the mother's circulatory system delivers oxygen and nutrients to the fetus and carries away nutrient-depleted blood enriched with carbon dioxide. The maternal and fetal blood circulations are separate and the exchange of molecules occurs through the placenta, in a region called intervillous space which is located in between maternal and fetal blood vessels.


title: Fetal hemoglobin

text: Focusing on oxygen exchange, there are 3 important aspects that allow it to pass from the maternal circulation into the fetal circulation. Firstly, the presence of hemoglobin F in the fetus allows a stronger binding to oxygen than maternal hemoglobin (see "Factors affecting oxygen affinity"). Secondly, the mother's bloodstream is richer in oxygen than that of the fetus, so oxygen naturally flows towards the fetal circulation by diffusion. The final factor is related to the effects of pH on maternal and fetal hemoglobin. As the maternal blood acquires more carbon dioxide, it becomes more acidic and this favors the release of oxygen by the maternal hemoglobin. At the same time, the decrease in carbon dioxide in fetal blood makes it more alkaline and favors the uptake of oxygen. This is called the Bohr effect or Haldane effect, which also happens in the air exchange in the lungs. All of these 3 factors are present simultaneously and cooperate to improve the fetus’ access to oxygen from the mother.


title: Fetal hemoglobin

text: F-cells are the subpopulation of red blood cells that contain hemoglobin F, in amongst other types of hemoglobin. While common in fetuses, in normal adults, only around 3-7% of red blood cells contain hemoglobin F. The low percentage of F-cells in adults owes to two factors: very low levels of hemoglobin F being present and its tendency to be produced only in a subset of cells rather than evenly distributed amongst all red blood cells. In fact, there is a positive correlation between the levels of hemoglobin F and number of F-cells, with patients with higher percentages of hemoglobin F also having a higher proportion of F-cells. Despite the correlations between hemoglobin F levels and F-cell numbers, usually they are determined by direct measurements. While the amount of hemoglobin F is calculated using cell lysates, which are fluids with contents of cells that were broken open, F-cell numbers are done by counting intact red blood cells.


title: Fetal hemoglobin

text: Due to the correlation between the amount of hemoglobin F and F-cells, F-cell numbers are higher in some inherited hemoglobin disorders, including beta-thalassemia, sickle cell anemia and hereditary persistence of fetal hemoglobin. Additionally, some acquired conditions can also have higher F-cell numbers, such as acute erythropoietic stress (response to poor oxygenation which includes very rapid synthesis of new red blood cells) and pregnancy.


title: Fetal hemoglobin

text: F-cells have similar mass of haemoglobin per cell compared to red blood cells without haemoglobin F, which is measured mean cell haemoglobin values (MCH).


title: Fetal hemoglobin

text: There is a significant increase in hemoglobin F levels during early pregnancy. However, it's not clear whether these levels are stable or decrease as the pregnancy goes on, as different sources reported different results.


title: Fetal hemoglobin

text: The increase in hemoglobin F then induces a 3 to 7 fold increase in the number of F-cells in pregnant women, which was observed between the 23rd to 31st week of gestation.


title: Fetal hemoglobin

text: However, as to the reason of the increase in hemoglobin F levels in pregnant women, there doesn't seem to be conclusive evidence. While an early study suggested that maternal red blood cells switch on hemoglobin F production during pregnancy, more recent literature suggested that the increase in haemoglobin F could be, at least in part, due to fetal red blood cells being transferred to the maternal circulation.


title: Fetal hemoglobin

text: Presence of high levels of hemoglobin F in pregnant women can impact the growth of the fetus, as fetal red blood cells struggle to compete for the oxygen from the mother's circulation. This is because instead of competing with hemoglobin A, which has a weaker association to oxygen than hemoglobin F, it becomes a competition between fetal and maternal hemoglobin F which have similar affinities for oxygen. As a result, women with hemoglobin F as >70% of total hemoglobin are much more likely to have fetuses that are small for their gestational age compared women with <70% hemoglobin F (at a rate of 100% compared to 8%, respectively).


title: Fetal hemoglobin

text: This is a rare benign genetic disease where production of hemoglobin F persists after twelve months of life and into the adulthood. As a result, hemoglobin F is present in a higher number of adult red blood cells than normal.


title: Fetal hemoglobin

text: It doesn't present symptoms and is usually discovered when screening for other blood-related diseases.


title: Fetal hemoglobin

text: In this condition, the genes coding for the γ subunit (HBG1 and HBG2) are not suppressed shortly before birth. This can happen when a mutation occurs in the promoter region of HBG1 and HBG2, preventing the binding of BCL11A and ZBTB7A proteins. These proteins would normally bind and suppress the production of γ subunits and as they can't bind due to the mutation, γ subunits continue to be produced. There are two types of patients with HPFH: either with one normal copy of the gene and one disease form or with two disease copies. Whereas normal adults have less than 1% of hemoglobin F, patients with only one disease gene have 5-30%. Patients with two disease copies can have hemoglobin F in up to 100% of red blood cells.


title: Fetal hemoglobin

text: As other diseases such as sickle cell disease could also cause a higher level of hemoglobin F to be present, it can sometimes be misdiagnosed.


title: Fetal hemoglobin

text: Delta beta-thalassemia is a rare genetic blood disorder in which the production of both δ and β subunits are reduced or absent. In these cases, the production of the γ subunit increases to compensate for the loss of δ and β subunits, resulting in a higher amount of hemoglobin F present in the blood. Normally, people have two sets of genes for producing δ and β subunits. People with only one set of working genes don't get any symptoms and in the rarely reported cases where both sets of genes are affected, the patients only experienced mild symptoms.


title: Fetal hemoglobin

text: The discovery that hemoglobin F alleviated the symptoms of sickle cell disease occurred in 1948. Janet Watson observed that red blood cells from infants with the disease took longer to sickle and did not deform as much compared to their mother's cells, which carried the disease trait. Later, it was noted that patients with sickle cell trait as well as hereditary persistence of hemoglobin F (HPFH) didn't have symptoms. Additionally, in sickle cell patients, F-cells were found to be more long living than non-F cells as they contain hemoglobin F.


title: Fetal hemoglobin

text: When fetal hemoglobin production is switched off after birth, normal children begin producing adult hemoglobin (HbA). Children with sickle-cell disease begin producing a defective form of hemoglobin called hemoglobin S instead, which form chains that cause red blood cells to change their shape from round to sickle-shaped.


title: Fetal hemoglobin

text: These defective red blood cells have a much shorter life span than normal red blood cells (10–20 days compared to up to 120 days). They also have a greater tendency to clump together and block small blood vessels, preventing blood supply to tissues and organs. This leads to the so-called "vaso-occlusive crisis", which is a hallmark of the disease.


title: Fetal hemoglobin

text: If fetal hemoglobin remains relatively high after birth, the number of painful episodes decreases in patients with sickle-cell disease and they have a better prognosis.


title: Fetal hemoglobin

text: Fetal hemoglobin's role in reducing disease severity comes from its ability to disrupt the formation of hemoglobin S chains within red blood cells.


title: Fetal hemoglobin

text: Interestingly, while higher levels of hemoglobin F were associated with improvement of some symptoms, including the frequency of painful episodes, leg ulcers and the general severity of the disease, it had no correlation to others. A few examples are priapism, stroke and systemic blood pressure. As hemoglobin F are only produced by some red blood cells, in different quantities, only a subpopulation of cells are protected against sickling. It could be that the symptoms that high hemoglobin F doesn't prevent are quite sensitive to the rupture of the sickled non-F cells.


title: Fetal hemoglobin

text: Hydroxyurea is a chemical that promotes the production of fetal hemoglobin and reduces the premature rupturing of red blood cells. Combination therapy with hydroxyurea and recombinant erythropoietin — rather than treatment with hydroxyurea alone — has been shown to further elevate hemoglobin F levels and to promote the development of HbF-containing F-cells.


title: Fetal hemoglobin

text: There have been some studies evaluating the possibility of using hemoglobin F as an indicator of the prognosis for cancer. It has been suggested that elevated concentrations of haemoglobin F can be found in main kinds of solid tumours and blood cancers.


title: Fetal hemoglobin

text: Examples include acute lymphoblastic leukemia and myeloid leukemia in children, where higher concentrations of hemoglobin F were associated with a worse outcome, including a higher risk of relapse or death.


title: Fetal hemoglobin

text: Other cancer types where higher hemoglobin F levels have been observed are transitional cell cancer, colorectal carcinoma


title: Fetal hemoglobin

text: and various types of blastomas. In fact, in several types of blastomas, including neuroblastoma and retinoblastoma (affecting the nerve cells and the eyes, respectively), F-cells were found in newly formed blood vessels and spaces in between tumour cells. Clusters of F-cells were also present in the bone marrow of some of these patients.


title: Fetal hemoglobin

text: Interestingly, hemoglobin F is not directly produced by tumour cells, but seems to be induced by the biological environment of the cancer in nearby blood cells. A reason suggested for this increase in hemoglobin F is that it may favor cancer growth by providing better oxygen supply to the developing cancerous cells. In adults, increased hemoglobin F production is thought to be caused by factors leading to the activation of the gene coding for the γ subunit, such as DNA demethylation (which can activate normally silent genes and is a hallmark of cancer.


title: Titan Airways

text: Titan Airways is a British charter airline founded in 1988 and based at London Stansted Airport. The carrier specialises in short-notice ACMI (aircraft, crew, maintenance, and insurance) and wet lease operations as well as ad-hoc passenger and cargo charter services to tour operators, corporations, governments and the sports and entertainment sectors. The company holds a United Kingdom Civil Aviation Authority Type A Operating Licence, permitting it to carry passengers, cargo and mail on aircraft with 20 or more seats.


title: Titan Airways

text: Founded in 1988 as a subsidiary of the Artac Freight and Shipping Group, Titan Airways was named after its first aircraft type, a Cessna 404 Titan, however, the airline's logo draws reference to Titan, a moon of Saturn. Their Cessna 404 aircraft were mainly used to carry car parts between various Ford/General Motors facilities in the UK and Europe, but it was also available for ad hoc freight charters and ultimately passenger charters. By 1993, the fleet had grown to include an Embraer Emb 110 Bandeirante, two Short SD 330s and three SD 360s.


title: Titan Airways

text: The airline's success attracted investment group 3i which took a stake in the company in 1995. Two ATR 42s were also added before the first jet – a BAe 146-200QC – was acquired in 1996. This was the first containerised jet used by the Royal Mail, but it also operated many passenger charter flights and airline sub-services. As the Mail contract grew in size, the first of five Boeing 737-300s was introduced in 1999.


title: Titan Airways

text: The airline has been consistently profitable, turning a profit in 24 of its 27-year history and has ranked in the "Sunday Times" Profit Track 100 league table on four occasions since the year 2000. In the early 2000s (decade) Titan Airways found an additional niche in the market, pioneering a rapid response Go Now sub-charter service for airlines experiencing operational problems. The innovative concept earned the company Queen's Award for Enterprise in 2001.


title: Titan Airways

text: Demand by customer airlines for more seats and greater range led to the acquisition of two 757-200s in 2003 and 2005, with one aircraft having a VIP interior for corporate use. In 2006 Titan achieved ETOPS rating for the aircraft, enabling long haul charters to the US and Middle East. The largest aircraft in the Titan family, a 265-seat B767-300, joined the fleet in 2009, and the smallest, a new Cessna Citation CJ2+ arrived in December 2011.


title: Titan Airways

text: In 2012 Titan became an independent company, following a management buyout that left Gene Willson, Managing Director and one of the original founders, as the sole share holder.


title: Titan Airways

text: Titan added its first Airbus aircraft, an Airbus A320, to its fleet in early Spring 2013. This addition was the first step in its long-term fleet strategy which will see Titan's current fleet of Boeing aircraft gradually being replaced by Airbus aircraft over the next five to six years. Two additional A320s joined the fleet in early 2015.


title: Titan Airways

text: September 2015 saw Titan announce plans to add an Airbus A319 and Airbus A321 to the fleet before the start of summer 2016 and that they were considering adding the smallest member of the Airbus A320 family, an Airbus A318, to their fleet.


title: Titan Airways

text: Titan Airways provides short, medium or long term wet and damp lease operations worldwide to third party carriers.


title: Titan Airways

text: The UK carrier also operates short notice sub-charter services, with the ability to launch aircraft within 60 minutes when airline customers experience unexpected operational problems.


title: Titan Airways

text: Titan Airways operates charter flights on a seasonal basis to a number of destinations on behalf of UK-based tour operators and cruise companies. Longstanding tour operator partnerships include regular operations from UK airports to Calvi in Corsica, Lourdes and Chambéry in France, Turin in Italy, Dalaman in Turkey, Preveza in Greece and Banjul in the Gambia.


title: Titan Airways

text: Aside from these regular seasonal routes, Titan Airways operates long and short haul flights on an ad hoc basis on behalf of individuals, blue chip companies, Premier League football teams, high-profile personalities and pop/rock groups. In September 2021, after a 19 months hiatus in filming due to the COVID-19 pandemic, season 33 of the USA TV series "The Amazing Race" resumed. For the safety of the racers and the crew, instead of going back to taking commercial flights as they had done in the past, they used a Titan Airways Boeing 757 with an "Amazing Race" livery.


title: Titan Airways

text: Titan Airways sometimes uses their aircraft in product launches, trade shows, promotional events and hospitality trips for other companies.


title: Titan Airways

text: Titan Airways’ cooperation with the Royal Mail dates back to the early 1990s when operations began with the carrier's Short 360 and ATR 42 aircraft. In 1996 the carrier's BAe 146-200 fleet superseded the smaller aircraft before being joined, and ultimately replaced, by Titan's Boeing 737-300QCs. The aircraft operated on behalf of the Royal Mail with nightly flights from Stansted to Edinburgh and to Belfast.


title: Titan Airways

text: Titan Airways carries out flights for Home Office and the Foreign Office of the Government of the United Kingdom.


title: Titan Airways

text: On 30 July 2020, Titan Airways' Boeing 757 became the largest passenger aircraft to land and depart from Saint Helena Airport. This flight was a repatriation mission on behalf of the British Government. A series of flights to Saint Helena and Ascension Island, once per month during the rest of 2020 and 2021, were performed with the same aircraft type. On 11 January 2021, one of Titan's Boeing 757 aircraft delivered 100 coronavirus vaccines to Saint Helena.


title: Titan Airways

text: Titan Airways' Boeing 767 operated to the Falkland Islands on behalf of the UK Ministry of Defence for two years until September 2012, with twice-weekly flights departing from RAF Brize Norton, in Oxfordshire, to RAF Mount Pleasant via RAF Ascension Island. In 2014 Titan Airways' RJ100 aircraft had been based in Sharjah on contract to the UK MoD since 2011. The RJ100 superseded Titan Airways' BAe 146 operations in the Persian Gulf region which dated back to 2009.