title: T.N.T. (album)

text: T.N.T. is the second studio album by Australian hard rock band AC/DC, released only in Australia, on 1 December 1975. This was the band's first release with bassist Mark Evans and drummer Phil Rudd, although the last two tracks feature George Young and Tony Currenti, both of whom previously appeared on "High Voltage".


title: T.N.T. (album)

text: After the success of the single "Baby, Please Don't Go" and the album "High Voltage", AC/DC returned to Albert Studios in Sydney to record their second LP with producers George Young and Harry Vanda. George was the older brother of guitarists Malcolm Young and Angus Young and had enjoyed his own success in the group the Easybeats. "T.N.T." marked a change in direction from AC/DC's debut album, "High Voltage", which was released on 17 February 1975; whereas "High Voltage" featured some experimentation with the styles of its songs and had a variety of personnel filling multiple roles, "T.N.T." saw the band fully embrace the formula for which they would become famous: hard-edged, rhythm and blues-based rock and roll. They also simplified their personnel system and would use it from then on out, which was Angus strictly playing lead guitar, Malcolm Young playing rhythm guitar, and the drummer and bassist being the only ones to play drums and bass guitar respectively on the albums. In Murray Engleheart's book "AC/DC: Maximum Rock & Roll", producer Harry Vanda states, "I suppose there might have been one or two tracks on the first album, a few things that they were experimenting with, which probably later on they wouldn't have done anymore. So I suppose you could say that "T.N.T" was the one that really pulled the identity; like, this is AC/DC, there's no doubt about it, that's who it's going to be and that's how it's going to stay."


title: T.N.T. (album)

text: In Clifton Walker's 1994 book "Highway to Hell: The Life and Times of AC/DC Legend Bon Scott", bassist Mark Evans speaks about the band's creative process during this period:


title: T.N.T. (album)

text: "It's a Long Way to the Top (If You Wanna Rock 'n' Roll)" was edited down from an extended jam by producer George Young and the inclusion of the bagpipes was his idea to add an extra dynamic to the track. Singer Bon Scott had played in a pipe band in his teens, so George suggested he play bagpipes on the song, not realizing that Scott had been a drummer, not a piper. Regardless, Scott – who knew how to play the recorder – learned the instrument and went on to play them on stage with the band up until 1976, when he set the bagpipes down on the corner of the stage and they were destroyed by fans. For the next three years, whenever they played the song live, Angus would play an extended guitar solo. Chanting in "T.N.T." was also George Young's idea, added after he heard Angus ad-libbing the "oi" chant to himself, and suggested he record it.


title: T.N.T. (album)

text: "T.N.T." contains some of the band's best-known songs, including the title track, "It's a Long Way to the Top", "The Jack", and "Rocker." Seven of the album's nine songs were written by the Young brothers and Scott, while "Can I Sit Next to You Girl" predated Scott's involvement in the band, having been recorded as a single with former vocalist Dave Evans. It features a different arrangement and slightly different lyrics from the original version. It also runs almost a minute longer. "School Days" is a cover version of a Chuck Berry song, a major influence on both Young brothers. "High Voltage" was the first song written and recorded for the album, the title inspired by that of the previous album. In 1993, Angus Young shared the origins of the title track with Vic Garbarini of "Guitar For the Practicing Musician": "I remember sitting home one night before going into the studio and playing around with some chords, and I suddenly thought, let's try playing...A...C...D...C. Sounded good. And then I thought AC/DC...power..."High Voltage"! I sang the chorus part to my brother in the studio and he thought it sounded great." Issued as the first single before the "T.N.T." sessions began, many fans thought it was from "High Voltage". Chris Gilbey of Albert Productions later claimed this caused a late surge in that album's sales. Lyrically, the LP features Bon Scott chronicling both the good and the bad about the rock and roll lifestyle, warning aspiring musicians that "it's harder than it looks" ("It's a Long Way to the Top") but also defiantly telling the moral majority to "stick your moral standards 'cause it's all a dirty lie" ("Rock 'n' Roll Singer"). In 1994, biographer Clifton Walker observed that Bon was "virtually encapsulating his entire life" in both songs. The lyrics of "The Jack," sometimes titled "(She's Got) The Jack," were developed by Scott, who was inspired by a letter Malcolm Young received during a tour of Adelaide. The letter, from a woman in Melbourne, implied that Malcolm had given her a venereal disease, although he claims that when he got tested, he was clean. Scott's original lyrics were far more explicit than those heard on the album, which he deliberately toned down in case the song got played on radio. The bravado-driven "Live Wire," which was also sexually suggestive, would be the band's show-opener for several years. Almost right from the beginning, the band was taken to task in some quarters for their "smutty" lyrics, as Angus acknowledged to "Guitar World"s Tom Beaujour in 1998:


title: T.N.T. (album)

text: I believe that the politically correct term is "sexist." Intellectuals like to put a tag on it and say, "these guys are out-and-out sexist." I've always found there's a two-sided thing when it comes to lyrics: someone can call a song "Sexy Motherfucker," and be accepted, and yet we've been writing all songs all these years, and while there may be the rare "fuck" in the lyrics there somewhere, it's all been quite clean cut. Still, people just make the assumption that we're five guys who've just got our dicks in mind. People have frequently commented that for all the notoriety and things we got involved in, we could have capitalized on our reputation and said, "Oh yeah, we're a piece of nasty work." But why bother?


title: T.N.T. (album)

text: "T.N.T." also led to more AC/DC appearances on Australia's "Countdown" music programme, following those in support of the Australian "High Voltage" album. These appearances included a live performance of the song "T.N.T.", as well as a music video for "It's a Long Way to the Top (If You Wanna Rock 'n' Roll)". Filmed on 1976, the video featured the band's then-current lineup, along with members of the Rats of Tobruk Pipe Band, on the back of a flat-bed truck travelling on Swanston Street in Melbourne. On 2004, Melbourne's Corporation Lane was renamed AC/DC Lane as a tribute to AC/DC, with the decision being based in part on this video.


title: T.N.T. (album)

text: "T.N.T." was originally released by Albert Productions, and has never been reissued by another label. Furthermore, it is the only Australian AC/DC studio album for which there is no international counterpart. However, seven of its nine songs comprise the international version of "High Voltage", released in May 1976. The other two, "Rocker" and "School Days", saw worldwide release as part of "Dirty Deeds Done Dirt Cheap"'s international version (1976/1981) and the "Bonfire" box set (1997) respectively.


title: T.N.T. (album)

text: Two singles were released from the album – "It's a Long Way to the Top (If You Wanna Rock 'n' Roll)" (December 1975) and "T.N.T." (March 1976). "T.N.T." was released in a gatefold sleeve, with the inside depicting the various members on mock-ups of police identification cards, listing apparent aliases and partially obscured personal details including birthdates (only Bon Scott's is readily visible and Angus Young's birth year is incorrectly shown as 1959, not 1955, in keeping with his schoolboy persona as this made him appear 16 instead of his real age of 20).


title: T.N.T. (album)

text: The original 1975 LP release featured longer versions of "Can I Sit Next to You Girl", "High Voltage" and "Rocker" compared to the versions heard on later CD releases:


title: T.N.T. (album)

text: Eduardo Rivadavia of AllMusic calls "T.N.T." "a stellar album in its own right, and especially crucial in that it marked AC/DC's definitive break with their now seemingly heretical glam rock inclinations, in order to embrace the blue collar hard rock that would forever after be their trademark."


title: Lizzy McAlpine

text: Elizabeth Catherine McAlpine, also known as Lizzy McAlpine (born September 21, 1999) is an American singer-songwriter.


title: Lizzy McAlpine

text: Lizzy McAlpine grew up in the suburbs of Philadelphia, Pennsylvania. She has written music since she was in 6th grade. She attended Lower Merion High School, where she sang in a co-ed a cappella group and did theater.


title: Lizzy McAlpine

text: McAlpine studied songwriting at Berklee College of Music located in Boston before leaving in her junior year to pursue music full-time. In April 2020 at the beginning of the COVID-19 pandemic, she started the Instagram #BerkleeAtHome streaming concert series.


title: Lizzy McAlpine

text: In 2018, McAlpine released her debut EP, "Indigo". She studied in Spain in the fall of 2019, where she wrote her debut studio album, "Give Me a Minute". The album was released in August 2020, to critical acclaim. The album has been streamed millions of times on Spotify and other digital service providers. The "Dallas Observer" named it one of the best albums of 2020, and BBC Media Centre has called her an "up-and-coming vocalist". In April 2021, McAlpine released an 8-song EP, "When the World Stopped Moving: The Live EP". She made her late-night debut on November 22, 2021, performing "Erase Me" on "Jimmy Kimmel Live!".


title: Lizzy McAlpine

text: McAlpine has garnered supporters from TikTok and Instagram, with several publications calling her a "TikTok star". Her unreleased song "You Ruined the 1975", posted in June 2020, has over 8 million views on TikTok as of April 2021.


title: Lizzy McAlpine

text: McAlpine released her second studio album, "Five Seconds Flat" on April 8, 2022. The album debuted at number five on US "Billboard Heatseekers" chart, while also peaking at number nine on Alternative New Artist Albums and number 19 on Top New Artist Albums charts.


title: Lizzy McAlpine

text: Her musical style has been described as "folk-focused", "folk-pop", and a blend of "jazz, pop, and R&B". Her collaborators include Jacob Collier, Dodie, Tom Rosenthal, Ben Kessler, John Mayer, Finneas, and Thomas Headon.


title: Median income

text: The median income is the income amount that divides a population into two equal groups, half having an income above that amount, and half having an income below that amount. It may differ from the mean (or average) income. Both of these are ways of understanding income distribution.


title: Median income

text: Median income can be calculated by household income, by personal income, or for specific demographic groups.


title: Median income

text: The following table represents data from OECD's "median disposable income per person" metric; disposable income deducts from gross income the value of taxes on income and wealth paid and of


title: Median income

text: contributions paid by households to public social security schemes. The figures are equivalised by dividing income by the square root of household size. As OECD displays median disposable incomes in each country's respective currency, the values were converted here using PPP conversion factors for private consumption from the same source, accounting for each country's cost of living in the year that the disposable median income was recorded. Data are in United States dollars at current prices and current purchasing power parity for private consumption for the reference year.


title: The Tipping Point

text: The Tipping Point: How Little Things Can Make a Big Difference is the debut book by Malcolm Gladwell, first published by Little, Brown in 2000. Gladwell defines a tipping point as "the moment of critical mass, the threshold, the boiling point." The book seeks to explain and describe the "mysterious" sociological changes that mark everyday life. As Gladwell states: "Ideas and products and messages and behaviors spread like viruses do." The examples of such changes in his book include the rise in popularity and sales of Hush Puppies shoes in the mid-1990s and the steep drop in New York City's crime rate after 1990.


title: The Tipping Point

text: Gladwell describes the "three rules of epidemics" (or the three "agents of change") in the tipping points of epidemics.


title: The Tipping Point

text: "The Law of the Few" is, as Gladwell states: "The success of any kind of social epidemic is heavily dependent on the involvement of people with a particular and rare set of social gifts." According to Gladwell, economists call this the "80/20 Principle, which is the idea that in any situation roughly 80 percent of the 'work' will be done by 20 percent of the participants" (see Pareto Principle). These people are described in the following ways:


title: The Tipping Point

text: A similar theory to Gladwell's "Law of the Few" appears in Kurt Vonnegut's Bluebeard (1987). In Bluebeard chapter 24, Paul Slazinger is working his first volume of non-fiction titled "The Only Way to Have a Successful Revolution in Any Field of Human Activity." Specifically, Vonnegut's 1987 character describes: “The team must consist of three sorts of specialists, he says. Otherwise the revolution, whether in politics or the arts or the sciences or whatever, is sure to fail. The rarest of these specialists, he says, is an authentic genius - a person capable of having seemingly good ideas not in general circulation. "A genius working alone," he says, "is invariably ignored as a lunatic." The second sort of specialist is a lot easier to find; a highly intelligent citizen in good standing in his or her community, who understands and admires the fresh ideas of the genius, and who testifies that the genius is far from mad. "A person like this working alone," says Slazinger, "can only yearn loud for changes, but fail to say what their shaped should be." The third sort of specialist is a person who can explain everything, no matter how complicated, to the satisfaction of most people, no matter how stupid or pigheaded they may be. "He will say almost anything in order to be interesting and exciting," says Slazinger. "Working alone, depending solely on his own shallow ideas, he would be regarded as being as full of shit as a Christmas turkey.”


title: The Tipping Point

text: The Stickiness Factor refers to the specific content of a message that renders its impact memorable. Popular children's television programs such as "Sesame Street" and "Blue's Clues" pioneered the properties of the stickiness factor, thus enhancing effective retention of educational content as well as entertainment value. Gladwell states, "Kids don't watch when they are stimulated and look away when they are bored. They watch when they understand and look away when they are confused" (Gladwell, p. 102).


title: The Tipping Point

text: Human behavior is sensitive to and strongly influenced by its environment. Gladwell explains: "Epidemics are sensitive to the conditions and circumstances of the times and places in which they occur." For example, "zero tolerance" efforts to combat minor crimes such as fare-beating and vandalism of the New York subway led to a decline in more violent crimes citywide. Gladwell describes the bystander effect, and explains how Dunbar's number plays into the tipping point, using Rebecca Wells' novel "Divine Secrets of the Ya-Ya Sisterhood", evangelist John Wesley, and the high-tech firm W. L. Gore and Associates. Dunbar's number is the maximum number of individuals in a society or group that someone can have real social relationships with, which Gladwell dubs the "rule of 150."


title: The Tipping Point

text: Gladwell also includes two chapters of case studies, situations in which tipping point concepts were used in specific situations. These situations include the athletic shoe company Airwalk, the diffusion model, how rumors are spread, decreasing the spread of syphilis in Baltimore, teen suicide in Micronesia, and teen smoking in the United States.


title: The Tipping Point

text: Gladwell received an estimated US$1–1.5 million advance for "The Tipping Point", which sold 1.7 million copies by 2006. In the wake of the book's success, Gladwell was able to earn as much as $40,000 per lecture. Sales increased again in 2006 after the release of Gladwell's next book, "Blink". "The Guardian" ranked "The Tipping Point" #94 in its list of 100 Best Books of the 21st Century.


title: The Tipping Point

text: Some of Gladwell's analysis as to why the phenomenon of the "tipping point" occurs (particularly in relation to his idea of the "law of the few") and its unpredictable elements is based on the 1967 small-world experiment by social psychologist Stanley Milgram. Milgram distributed letters to 160 students in Nebraska, with instructions that they be sent to a stockbroker in Boston (not personally known to them) by passing the letters to anyone else that they believed to be socially closer to the target. The study found that it took an average of six links to deliver each letter. Of particular interest to Gladwell was the finding that just three friends of the stockbroker provided the final link for half of the letters that arrived successfully. This gave rise to Gladwell's theory that certain types of people are key to the dissemination of information.


title: The Tipping Point

text: In 2003, Duncan Watts, a network theory physicist at Columbia University, repeated the Milgram study by using a web site to recruit 61,000 people to send messages to 18 targets worldwide. He successfully reproduced Milgram's results (the average length of the chain was approximately six links). However, when he examined the pathways taken, he found that "hubs" (highly connected people) were not crucial. Only 5% of the e-mail messages had passed through one of the hubs. This casts doubt on Gladwell's assertion that specific types of people are responsible for bringing about large levels of change.


title: The Tipping Point

text: Watts pointed out that if it were as simple as finding the individuals that can disseminate information prior to a marketing campaign, advertising agencies would presumably have a far higher success rate than they do. He also stated that Gladwell's theory does not square with much of his research into human social dynamics performed in the last ten years.


title: The Tipping Point

text: Economist Steven Levitt and Gladwell have a running dispute about whether the fall in New York City's crime rate can be attributed to the actions of the police department and "Fixing Broken Windows" (as claimed in "The Tipping Point"). In "Freakonomics", Levitt attributes the decrease in crime to two primary factors: 1) a drastic increase in the number of police officers trained and deployed on the streets and hiring Raymond W. Kelly as police commissioner (thanks to the efforts of former mayor David Dinkins) and 2) a decrease in the number of unwanted children made possible by "Roe v. Wade", causing crime to drop nationally in all major cities—"[e]ven in Los Angeles, a city notorious for bad policing". And although psychologist Steven Pinker argues the second factor relies on tenuous links, recent evidence seems to uphold the likelihood of a significant causal link.


title: L.V. (singer)

text: Larry J. Sanders (born December 2, 1960), known professionally as L.V. (an acronym for "Large Variety"), is an American singer. He is best known for his collaboration with rapper Coolio on the single "Gangsta's Paradise", which has been featured on multiple soundtracks since then. He has released five solo albums and was a member of the gangsta rap group South Central Cartel since it formed, usually singing the choruses.


title: Sweet sixteen (birthday)

text: A sweet sixteen is a coming of age party celebrating a person's 16th birthday, mainly celebrated in some parts of the United States and Canada. While some families throw large, lavish celebrations, others choose to celebrate the birthday as if it were a normal occurrence. This event can be formal, casual, or semi-formal.


title: Sweet sixteen (birthday)

text: While traditionally it is common that sweet sixteens are mostly celebrated by girls, they can also be celebrated by boys. Sweet sixteens can range from modest parties at home with close family to large parties with a hired DJ, makeup, hair styling, expensive gowns and dresses, and hotel ballrooms. Even if it is a small party, the main purpose of the party is to celebrate the person's earliest stage of adulthood.


title: Sweet sixteen (birthday)

text: Alternative sweet sixteen celebrations in the United States can include a religious or church ceremony also, like a Mass or a blessing at church. This religious or church ceremony has its origins in the Quinceañera style, but since there are many American-born Hispanic people, many choose to blend a sweet sixteen American style with their Quinceañera tradition. For example, the girl may go to the church for the religious ceremony and, then, while in the party, choose to have the sixteen-candle ceremony. The religious ceremony comes from the Hispanic tradition, while the sixteen candles ceremony comes from the American tradition.


title: Sweet sixteen (birthday)

text: For girls, the shoe ceremony is common at Quinceañeras parties. In this ceremony, the birthday girl sits down in a chair while her father, grandfather, Godfather, Uncle, or brother approaches her with high heels on a decorative pillow. The girl would traditionally be wearing flat shoes, such as slippers, and the father ceremoniously helps her into her new high heels. This is symbolic of the girl transitioning into a woman.


title: Sweet sixteen (birthday)

text: The tiara ceremony is similar to the shoe ceremony, except the mother or a strong female figure approaches with a tiara instead of shoes and places it on her daughter's head to symbolize her becoming a woman. Sometimes this is combined with the shoe ceremony so that two people approach the birthday girl, one with a pillow with high heels, and the other with a pillow with a tiara.


title: Sweet sixteen (birthday)

text: The father-daughter dance is a tradition that is also frequently performed at weddings. The girl and her father dance to a slow-jazz or traditional song while everyone sits and watches. This is usually the first song of the night. Sometimes, girls also added a mother-daughter dance as a dedication to her mother.


title: Sweet sixteen (birthday)

text: This tradition is most common in Bar and Bat Mitzvahs, Quinceaneras and sweet sixteens, although in different ages. There are typically 16 candles, each of which are given to special family members and friends by the birthday girl. Usually, when the recipient of the candle is named, a few words are said by the birthday girl in regards to why this person (or people) is special to them, they may tell a short story or fun memory they have shared with that person. Although the birthday girl can decide to give her candles to whomever she chooses, in whichever order she wants, here is the traditional order of candles:


title: Sweet sixteen (birthday)

text: In Canada and many states in the United States, the minimum age to legally drive a car is 16. Sometimes, although rarely, the birthday person is gifted a car as a birthday present. The car can be either purchased new, used, or simply be gifted from one person to another (often within their family).


title: Sweet sixteen (birthday)

text: Similar celebrations are found in different cultures around the world, such as the quinceañera in Hispanic countries and the "festa de debutantes" in Brazil, both at 15 years of age.


title: Sweet sixteen (birthday)

text: In the Philippines, the debut (pronounced "'de-boo") celebrates a young woman's 18th birthday. A young man may also celebrate his own debut on his 21st birthday, albeit with less formal celebrations or none at all.


title: Sweet sixteen (birthday)

text: Coming of Age Day (成人の日, Seijin no Hi) is a Japanese holiday held annually. It is held in order to congratulate and encourage all those who have reached or will reach the age of maturity. Festivities include coming of age ceremonies (成人式, seijin-shiki) held at local and prefectural offices, as well as after-parties among family and friends.


title: Sweet sixteen (birthday)

text: In Conservative and Orthodox Judaism, girls reach maturity at the age of 12, celebrated with a bat mitzvah, and for boys (and girls, in the Reform movement) at the age of 13, with a bar mitzvah, or for both, with a B'nai mitzvah and both girls, with a b'not mitzvah. These are important dates in the Jewish culture, because following these ceremonies, bar or bat mitzvah, the young person is considered an adult.


title: Sweet sixteen (birthday)

text: In many Christian denominations, both girls and boys reach the age of spiritual maturity at around the age of 13 or 14, with the Sacrament of Confirmation.


title: Hanlim Multi Art School

text: Hanlim School was founded on 3 March 1962, with Lee Hyeon-man being appointed school principal. In 2009, it became the Hanlim Multi Arts High School. It is known as one of the schools attended by current and future members of the South Korean entertainment industry, alongside the School of Performing Arts Seoul and Lila Art High School. Due to the fame of some of their students, the school is sometimes the subject of press, especially during graduation ceremonies.


title: Pelagianism

text: Pelagianism is a Christian theological position that holds that the original sin did not taint human nature and that humans by divine grace have free will to achieve human perfection. Pelagius ( – AD), an ascetic and philosopher from the British Isles, taught that God could not command believers to do the impossible, and therefore it must be possible to satisfy all divine commandments. He also taught that it was unjust to punish one person for the sins of another; therefore, infants are born blameless. Pelagius accepted no excuse for sinful behaviour and taught that all Christians, regardless of their station in life, should live unimpeachable, sinless lives.


title: Pelagianism

text: To a large degree, "Pelagianism" was defined by its opponent Augustine, and exact definitions remain elusive. Although Pelagianism had considerable support in the contemporary Christian world, especially among the Roman elite and monks, it was attacked by Augustine and his supporters, who had opposing views on grace, predestination and free will. Augustine proved victorious in the Pelagian controversy; Pelagianism was decisively condemned at the 418 Council of Carthage and is still regarded as heretical by the Roman Catholic Church and Eastern Orthodox Church. For centuries afterward, "Pelagianism" was used in various forms as a pejorative accusation of heresy for Christians who hold unorthodox beliefs, but it has undergone reassessment by recent scholarship.


title: Pelagianism

text: During the fourth and fifth centuries, the Church was experiencing rapid change due to the Constantinian shift to Christianity. Many Romans were converting to Christianity, but they did not necessarily follow the faith strictly. As Christians were no longer persecuted, they faced a new problem: how to avoid backsliding and nominal adherence to the state religion while retaining the sense of urgency originally caused by persecution. For many, the solution was adopting Christian asceticism.


title: Pelagianism

text: Early Christianity was theologically diverse. While Western Christianity taught that death was the result of the fall of man, a Syrian tradition, including the second-century figures Theophilus and Irenaeus, asserted that mortality preceded the fall. Around 400, the doctrine of original sin was just emerging in Western Christianity, deriving from the teaching of Cyprian that infants should be baptized for the sin of Adam. Other Christians followed Origen in the belief that infants are born in sin due to their failings in a previous life. Rufinus the Syrian, who came to Rome in 399 as a delegate for Jerome, followed the Syrian tradition, declaring that man had been created mortal and that each human is only punished for his own sin.


title: Pelagianism

text: Pelagius (–) was an ascetic layman, probably from the British Isles, who moved to Rome in the early 380s. Like Jerome, Pelagius criticized what he saw as an increasing laxity among Christians, instead promoting higher moral standards and asceticism. He opposed Manicheanism because of its fatalism and determinism and argued for the possibility of a sinless life. Although Pelagius preached the renunciation of earthly wealth, his ideas became popular among parts of Roman elite. Historian Peter Brown argued that Pelagianism appealed "to a powerful centrifugal tendency in the aristocracy of Rome—a tendency to scatter, to form a pattern of little groups, each striving to be an elite, each anxious to rise above their neighbours and rivals—the average upper‐class residents of Rome." The powerful Roman administrator Paulinus of Nola was close to Pelagius and the Pelagian writer Julian of Eclanum, and the former Roman aristocrat Caelestius was described by Gerald Bonner as "the real apostle of the so-called Pelagian movement". Many of the ideas Pelagius promoted were mainstream in contemporary Christianity, advocated by such figures as John Chrysostom, Athanasius of Alexandria, Jerome, and even the early Augustine.


title: Pelagianism

text: In 410, Pelagius and Caelestius fled Rome for Sicily and then North Africa due to the Sack of Rome by Visigoths. At the 411 Council of Carthage, Caelestius approached the bishop Aurelius for ordination, but instead he was condemned for his belief on sin and original sin. Caelestius defended himself by arguing that this original sin was still being debated and his beliefs were orthodox. His views on grace were not mentioned, although Augustine (who had not been present) later claimed that Caelestius had been condemned because of "arguments against the grace of Christ". Unlike Caelestius, Pelagius refused to answer the question as to whether man had been created mortal, and, outside of Northern Africa, it was Caelestius' teachings which were the main targets of condemnation. In 412, Augustine read Pelagius' "Commentary on Romans" and described its author as a "highly advanced Christian". Augustine maintained friendly relations with Pelagius until the next year, initially only condemning Caelestius' teachings, and considering his dispute with Pelagius to be an academic one.


title: Pelagianism

text: Jerome attacked Pelagianism for saying that humans had the potential to be sinless, and connected it with other recognized heresies, including Origenism, Jovinianism, Manichaeanism, and Priscillianism. Scholar Michael Rackett noted that the linkage of Pelagianism and Origenism was "dubious" but influential. Jerome also disagreed with Pelagius' strong view of free will. In 415, he wrote to refute Pelagian statements. Noting that Jerome was also an ascetic and critical of earthly wealth, historian Wolf Liebeschuetz suggested that his motive for opposing Pelagianism was envy of Pelagius' success. In 415, Augustine's emissary Orosius brought charges against Pelagius at a council in Jerusalem, which were referred to Rome for judgement. The same year, the exiled Gallic bishops Heros of Arles and Lazarus of Aix accused Pelagius of heresy, citing passages in Caelestius' . Pelagius defended himself by disavowing Caelestius' teachings, leading to his acquittal at the Synod of Diospolis in Lod, which proved to be a key turning point in the controversy. Following the verdict, Augustine convinced two synods in North Africa to condemn Pelagianism, whose findings were partially confirmed by Pope Innocent I. In January 417, shortly before his death, Innocent excommunicated Pelagius and two of his followers. Innocent's successor, Zosimus, reversed the judgement against Pelagius, but backtracked following pressure from the African bishops. Pelagianism was later condemned at the Council of Carthage in 418, after which Zosimus issued the excommunicating both Pelagius and Caelestius. Concern that Pelagianism undermined the role of the clergy and episcopacy was specifically cited in the judgement.


title: Pelagianism

text: At the time, Pelagius' teachings had considerable support among Christians, especially other ascetics. Considerable parts of the Christian world had never heard of Augustine's doctrine of original sin. Eighteen Italian bishops, including Julian of Eclanum, protested against the condemnation of Pelagius and refused to follow Zosimus' . Many of them later had to seek shelter with the Greek bishops Theodore of Mopsuestia and Nestorius, leading to accusations that Pelagian errors lay beneath the Nestorian controversy over Christology. Both Pelagianism and Nestorianism were condemned at the Council of Ephesus in 431. With its supporters either condemned or forced to move to the East, Pelagianism ceased to be a viable doctrine in the Latin West. Despite repeated attempts to suppress Pelagianism and similar teachings, some followers were still active in the Ostrogothic Kingdom (493–553), most notably in Picenum and Dalmatia during the rule of Theoderic the Great. Pelagianism was also reported to be popular in Britain, as Germanus of Auxerre made at least one visit (in 429) to denounce the heresy. Some scholars, including Nowell Myres and John Morris, have suggested that Pelagianism in Britain was understood as an attack on Roman decadence and corruption, but this idea has not gained general acceptance.


title: Pelagianism

text: The idea that God had created anything or anyone who was evil by nature struck Pelagius as Manichean. Pelagius taught that humans were free of the burden of original sin, because it would be unjust for any person to be blamed for another's actions. According to Pelagianism, humans were created in the image of God and had been granted conscience and reason to determine right from wrong, and the ability to carry out correct actions. If "sin" could not be avoided it could not be considered sin. In Pelagius' view, the doctrine of original sin placed too little emphasis on the human capacity for self-improvement, leading either to despair or to reliance on forgiveness without responsibility. He also argued that many young Christians were comforted with false security about their salvation leading them to relax their Christian practice.


title: Pelagianism

text: Pelagius believed that Adam's transgression had caused humans to become mortal, and given them a bad example, but not corrupted their nature, while Caelestius went even further, arguing that Adam had been created mortal. He did not even accept the idea that original sin had instilled fear of death among humans, as Augustine said. Instead, Pelagius taught that the fear of death could be overcome by devout Christians, and that death could be a release from toil rather than a punishment. Both Pelagius and Caelestius reasoned that it would be unreasonable for God to command the impossible, and therefore each human retained absolute freedom of action and full responsibility for all actions. Pelagius did not accept any limitation on free will, including necessity, compulsion, or limitations of nature. He believed that teaching a strong position on free will was the best motivation for individuals to reform their conduct.


title: Pelagianism

text: In the Pelagian view, by corollary, sin was not an inevitable result of fallen human nature, but instead came about by free choice and bad habits; through repeated sinning, a person could corrupt their own nature and enslave themself to sin. Pelagius believed that God had given man the Old Testament and Mosaic Law in order to counter these ingrained bad habits, and when that wore off over time God revealed the New Testament. However, because Pelagius considered a person to always have the ability to choose the right action in each circumstance, it was therefore theoretically possible (though rare) to live a sinless life. Jesus Christ, held in Christian doctrine to have lived a life without sin, was the ultimate example for Pelagians seeking perfection in their own lives, but there were also other humans who were without sin—including some notable pagans and especially the Hebrew prophets. This view was at odds with that of Augustine and orthodox Christianity, which taught that Jesus was the only man free of sin. Pelagius did teach Jesus' vicarious atonement for the sins of mankind and the cleansing effect of baptism, but placed less emphasis on these aspects.


title: Pelagianism

text: Pelagius taught that a human's ability to act correctly was a gift of God, as well as divine revelation and the example and teachings of Jesus. Further spiritual development, including faith in Christianity, was up to individual choice, not divine benevolence. Pelagius accepted no excuse for sin, and argued that Christians should be like the church described in Ephesians 5:27, "without spot or wrinkle". Instead of accepting the inherent imperfection of man, or arguing that the highest moral standards could only be applied to an elite, Pelagius taught that all Christians should strive for perfection. Like Jovinian, Pelagius taught that married life was not inferior to monasticism, but with the twist that all Christians regardless of life situation were called to a kind of asceticism. Pelagius taught that it was not sufficient for a person to call themselves a Christian and follow the commandments of scripture; it was also essential to actively do good works and cultivate virtue, setting themselves apart from the masses who were "Christian in name only", and that Christians ought to be extraordinary and irreproachable in conduct. Specifically, he emphasized the importance of reading scripture, following religious commandments, charity, and taking responsibility for one's actions, and maintaining modesty and moderation. Pelagius taught that true virtue was not reflected externally in social status, but was an internal spiritual state. He explicitly called on wealthy Christians to share their fortunes with the poor. (Augustine criticized Pelagius' call for wealth redistribution.)


title: Pelagianism

text: Because sin in the Pelagian view was deliberate, with people responsible only for their own actions, infants were considered without fault in Pelagianism, and unbaptized infants were not thought to be sent to hell. Like early Augustine, Pelagians believed that infants would be sent to purgatory. Although Pelagius rejected that infant baptism was necessary to cleanse original sin, he nevertheless supported the practice because he felt it improved their spirituality through a closer union with Jesus. For adults, baptism was essential because it was the mechanism for obtaining forgiveness of the sins that a person had personally committed and a new beginning in their relationship with God. After death, adults would be judged by their acts and omissions and consigned to everlasting fire if they had failed: "not because of the evils they have done, but for their failures to do good". He did not accept purgatory as a possible destination for adults. Although Pelagius taught that the path of righteousness was open to all, in practice only a few would manage to follow it and be saved. Like many medieval theologians, Pelagius believed that instilling in Christians the fear of hell was often necessary to convince them to follow their religion where internal motivation was absent or insufficient.


title: Pelagianism

text: Significant influences on Pelagius included Eastern Christianity, which had a more positive view of human nature, and classical philosophy, from which he drew the ideas of personal autonomy and self-improvement. Augustine accused Pelagius' idea of virtue of being "Ciceronian", because it overemphasized the role of human intellect and will. Although his teachings on original sin were novel, Pelagius' views on grace, free will and predestination were similar to those of contemporary Greek-speaking theologians such as Origen, John Chrysostom, and Jerome.


title: Pelagianism

text: Theologian Carol Harrison commented that Pelagianism is "a radically different alternative to Western understandings of the human person, human responsibility and freedom, ethics and the nature of salvation" which might have come about if Augustine had not been victorious in the Pelagian controversy. According to Harrison, "Pelagianism represents an attempt to safeguard God’s justice, to preserve the integrity of human nature as created by God, and of human beings' obligation, responsibility and ability to attain a life of perfect righteousness." However, this is at the expense of downplaying human frailty and presenting "the operation of divine grace as being merely external". According to scholar Rebecca Weaver, "what most distinguished Pelagius was his conviction of an unrestricted freedom of choice, given by God and immune to alteration by sin or circumstance."


title: Pelagianism

text: What Augustine called "Pelagianism" was more his own invention than that of Pelagius. According to Thomas Scheck, Pelagianism is the heresy of denying Catholic Church teaching on original sin, or more specifically the beliefs condemned as heretical in 417 and 418. In her study, Ali Bonner (a lecturer at the University of Cambridge) found that there was no one individual who held all the doctrines of "Pelagianism", nor was there a coherent Pelagian movement, although these findings are disputed. Bonner argued that the two core ideas promoted by Pelagius were "the goodness of human nature and effective free will" although both were advocated by other Christian authors from the 360s. Because Pelagius did not invent these ideas, she recommended attributing them to the ascetic movement rather than using the word "Pelagian". Later Christians used "Pelagianism" as an insult for theologically orthodox Christians who held positions that they disagreed with. Historian Eric Nelson defined genuine Pelagianism as rejection of original sin or denial of original sin's effect on man's ability to avoid sin. Even in recent scholarly literature, the term "Pelagianism" is not clearly or consistently defined.


title: Pelagianism

text: Pelagius' teachings on human nature, divine grace, and sin were opposed to those of Augustine, who declared Pelagius "the enemy of the grace of God". Augustine distilled what he called Pelagianism into three heretical tenets: "to think that God redeems according to some scale of human merit; to imagine that some human beings are actually capable of a sinless life; to suppose that the descendants of the first human beings to sin are themselves born innocent". In Augustine's writings, Pelagius is a symbol of humanism who excluded God from human salvation. Pelagianism shaped Augustine's ideas in opposition to his own on free will, grace, and original sin, and much of "The City of God" is devoted to countering Pelagian arguments. Another major difference in the two thinkers was that Pelagius emphasized obedience to God for fear of hell, which Augustine considered servile. In contrast, Augustine argued that Christians should be motivated by the delight and blessings of the Holy Spirit and believed that it was treason "to do the right deed for the wrong reason". According to Augustine, credit for all virtue and good works is due to God alone, and to say otherwise caused arrogance, which is the foundation of sin.


title: Pelagianism

text: According to Peter Brown, "For a sensitive man of the fifth century, Manichaeism, Pelagianism, and the views of Augustine were not as widely separated as we would now see them: they would have appeared to him as points along the great circle of problems raised by the Christian religion". John Cassian argued for a middle way between Pelagianism and Augustinianism, in which the human will is not negated but presented as intermittent, sick, and weak, and Jerome held a middle position on sinlessness. In Gaul, the so-called "semi-Pelagians" disagreed with Augustine on predestination (but recognized the three Pelagian doctrines as heretical) and were accused by Augustine of being seduced by Pelagian ideas. According to Ali Bonner, the crusade against Pelagianism and other heresies narrowed the range of acceptable opinions and reduced the intellectual freedom of classical Rome. When it came to grace and especially predestination, it was Augustine's ideas, not Pelagius', which were novel.


title: Pelagianism

text: According to Nelson, Pelagianism is a solution to the problem of evil that invokes libertarian free will as both the cause of human suffering and a sufficient good to justify it. By positing that man could choose between good and evil without divine intercession, Pelagianism brought into question Christianity's core doctrine of Jesus' act of substitutionary atonement to expiate the sins of mankind. For this reason, Pelagianism became associated with nontrinitarian interpretations of Christianity which rejected the divinity of Jesus, as well as other heresies such as Arianism, Socinianism, and mortalism (which rejected the existence of hell). Augustine argued that if man "could have become just by the law of nature and free will . . . amounts to rendering the cross of Christ void". He argued that no suffering was truly undeserved, and that grace was equally undeserved but bestowed by God's benevolence. Augustine's solution, while it was faithful to orthodox Christology, worsened the problem of evil because according to Augustinian interpretations, God punishes sinners who by their very nature are unable not to sin. The Augustinian defense of God's grace against accusations of arbitrariness is that God's ways are incomprehensible to mere mortals. Yet, as later critics such as Gottfried Wilhelm Leibniz asserted, asking "it is good and just because God wills it or whether God wills it because it is good and just?", this defense (although accepted by many Catholic and Reformed theologians) creates a God-centered morality, which, in Leibniz' view "would destroy the justice of God" and make him into a tyrant.


title: Pelagianism

text: One of the most important distinctions between Christianity and Judaism is that the former conventionally teaches justification by faith, while the latter teaches that man has the choice to follow divine law. By teaching the absence of original sin and the idea that humans can choose between good and evil, Pelagianism advocated a position close to that of Judaism. Pelagius wrote positively of Jews and Judaism, recommending that Christians study Old Testament (i.e., the Tanakh) law—a sympathy not commonly encountered in Christianity after Paul. Augustine was the first to accuse Pelagianism of "Judaizing", which became a commonly heard criticism of it. However, although contemporary rabbinic literature tends to take a Pelagian perspective on the major questions, and it could be argued that the rabbis shared a worldview with Pelagius, there were minority opinions within Judaism (such as the Essenes) which argued for ideas more similar to Augustine's. Overall, Jewish discourse did not discuss free will and emphasized God's goodness in his revelation of the Torah.


title: Pelagianism

text: The resolution of the Pelagian controversy gave rise to a new controversy in southern Gaul in the fifth and sixth centuries, retrospectively called by the misnomer "semi-Pelagianism". The "semi-Pelagians" all accepted the condemnation of Pelagius, believed grace was necessary for salvation, and were followers of Augustine. The controversy centered on differing interpretations of the verse : "For this is good and acceptable in the sight of God our Savior, who desires all men to be saved and to come to the knowledge of the truth." Augustine and Prosper of Aquitaine assumed that God's will is always effective and that some are not saved (i.e., opposing universal reconciliation). Their opponents, based on the tradition of Eastern Christianity, argued that Augustinian predestination contradicted the biblical passage. Cassian, whose writings survived, argued for prevenient grace that individuals could accept or reject. Other semi-Pelagians were said to undermine the essential role of God's grace in salvation and argue for a median between Augustinianism and Pelagianism, although these alleged writings are no longer extant. At the Council of Orange in 529, called and presided over by the Augustinian Caesarius of Arles, semi-Pelagianism was condemned but Augustinian ideas were also not accepted entirely: the synod advocated synergism, the idea that human freedom and divine grace work together for salvation.


title: Pelagianism

text: Christians often used "Pelagianism" as an insult to imply that the target denied God's grace and strayed into heresy. Later Augustinians criticized those who asserted a meaningful role for human free will in their own salvation as covert "Pelagians" or "semi-Pelagians".


title: Pelagianism

text: During the Middle Ages, Pelagius' writings were popular but usually attributed to other authors, especially Augustine and Jerome. Pelagius' "Commentary on Romans" circulated under two pseudonymous versions, "Pseudo-Jerome" (copied before 432) and "Pseudo-Primasius", revised by Cassiodorus in the sixth century to remove the "Pelagian errors" that Cassiodorus found in it. During the Middle Ages, it passed as a work by Jerome. Erasmus of Rotterdam printed the commentary in 1516, in a volume of works by Jerome. Erasmus recognized that the work was not really Jerome's, writing that he did not know who the author was. Erasmus admired the commentary because it followed the consensus interpretation of Paul in the Greek tradition. The nineteenth-century theologian Jacques Paul Migne suspected that Pelagius was the author, and William Ince recognized Pelagius' authorship as early as 1887. The original version of the commentary was found and published by Alexander Souter in 1926. According to French scholar , the Pelagian treatise "On the Christian Life" was the second-most copied work during the Middle Ages (behind Augustine's "The City of God") outside of the Bible and liturgical texts.


title: Pelagianism

text: During the modern era, Pelagianism continued to be used as an epithet against orthodox Christians. However, there were also some authors who had essentially Pelagian views according to Nelson's definition. Nelson argued that many of those considered the predecessors to modern liberalism took Pelagian or Pelagian-adjacent positions on the problem of evil. For instance, Leibniz, who coined the word theodicy in 1710, rejected Pelagianism but nevertheless proved to be "a crucial conduit for Pelagian ideas". He argued that "Freedom is deemed necessary in order that man may be deemed guilty and open to punishment." In , John Milton argued that "if, because of God's decree, man could not help but fall . . . then God's restoration of fallen man was a matter of justice not grace". Milton also argued for other positions that could be considered Pelagian, such as that "The knowledge and survey of vice, is in this world ... necessary to the constituting of human virtue." Jean-Jacques Rousseau made nearly identical arguments for that point. John Locke argued that the idea that "all "Adam"s Posterity [are] doomed to Eternal Infinite Punishment, for the Transgression of "Adam"" was "little consistent with the Justice or Goodness of the Great and Infinite God". He did not accept that original sin corrupted human nature, and argued that man could live a Christian life (although not "void of slips and falls") and be entitled to justification.


title: Pelagianism

text: Nelson argues that the drive for rational justification of religion, rather than a symptom of secularization, was actually "a Pelagian response to the theodicy problem" because "the conviction that everything


title: Pelagianism

text: necessary for salvation must be accessible to human reason was yet another inference from God's justice". In Pelagianism, libertarian free will is necessary but not sufficient for God's punishment of humans to be justified, because man must also understand God's commands. As a result, thinkers such as Locke, Rousseau and Immanuel Kant argued that following natural law without revealed religion must be sufficient for the salvation of those who were never exposed to Christianity because, as Locke pointed out, access to revelation is a matter of moral luck. Early modern proto-liberals such as Milton, Locke, Leibniz, and Rousseau advocated religious toleration and freedom of private action (eventually codified as human rights), as only freely chosen actions could merit salvation.


title: Pelagianism

text: 19th-century philosopher Søren Kierkegaard dealt with the same problems (nature, grace, freedom, and sin) as Augustine and Pelagius, which he believed were opposites in a Hegelian dialectic. He rarely mentioned Pelagius explicitly even though he inclined towards a Pelagian viewpoint. However, Kierkegaard rejected the idea that man could perfect himself.


title: Pelagianism

text: John Rawls was a critic of Pelagianism, an attitude that he retained even after becoming an atheist. His anti-Pelagian ideas influenced his book "A Theory of Justice", in which he argued that differences in productivity between humans are a result of "moral arbitrariness" and therefore unequal wealth is undeserved. In contrast, the Pelagian position would be that human sufferings are largely the result of sin and are therefore deserved. According to Nelson, many contemporary social liberals follow Rawls rather than the older liberal-Pelagian tradition.


title: Pelagianism

text: The conflict between Pelagius and the teachings of Augustine was a constant theme throughout the works of Anthony Burgess, in books including "A Clockwork Orange", "Earthly Powers", "A Vision of Battlements" and "The Wanting Seed".


title: Pelagianism

text: During the 20th century, Pelagius and his teachings underwent a reassessment. In 1956, John Ferguson wrote:


title: Pelagianism

text: Thomas Scheck writes that although Pelagius' views on original sin are still considered "one-sided and defective":


title: Doxorubicin

text: Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used together with other chemotherapy agents. Doxorubicin is given by injection into a vein.


title: Doxorubicin

text: Common side effects include hair loss, bone marrow suppression, vomiting, rash, and inflammation of the mouth. Other serious side effects may include allergic reactions such as anaphylaxis, heart damage, tissue damage at the site of injection, radiation recall, and treatment-related leukemia. People often experience red discoloration of the urine for a few days. Doxorubicin is in the anthracycline and antitumor antibiotic family of medications. It works in part by interfering with the function of DNA.


title: Doxorubicin

text: Doxorubicin was approved for medical use in the United States in 1974. It is on the World Health Organization's List of Essential Medicines. Versions that are pegylated and in liposomes are also available; however, they are more expensive. Doxorubicin was originally made from the bacterium "Streptomyces peucetius".


title: Doxorubicin

text: In the EU doxorubicin pegylated liposomal (as Caelyx) is indicated to treat breast cancer, ovarian cancer, and AIDS-related Kaposi's sarcoma. It is indicated to treat multiple myeloma in combination with bortezomib. Doxorubicin hydrochloride (as Myocet liposomal) is indicated to treat breast cancer in combination with cyclophosphamide.


title: Doxorubicin

text: Doxorubicin is commonly used to treat some leukemias and Hodgkin's lymphoma, as well as cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and others. Commonly used doxorubicin-containing regimens are AC (Adriamycin, cyclophosphamide), TAC (taxotere, AC), ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), BEACOPP, CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone) and FAC (5-fluorouracil, adriamycin, cyclophosphamide).


title: Doxorubicin

text: Doxil (see below) is used primarily for the treatment of ovarian cancer where the disease has progressed or recurred after platinum-based chemotherapy, or for the treatment of AIDS-related Kaposi's sarcoma.


title: Doxorubicin

text: The most dangerous side effect of doxorubicin is dilated cardiomyopathy, leading to congestive heart failure. The rate of cardiomyopathy is dependent on its cumulative dose, with an incidence about 4% when the dose of doxorubicin is 500–550 mg/m, 18% when the dose is 551–600 mg/m and 36% when the dose exceeds 600 mg/m. There are several ways in which doxorubicin is believed to cause cardiomyopathy, including oxidative stress, downregulation of genes for contractile proteins, and p53-mediated apoptosis.


title: Doxorubicin

text: Doxorubicin-induced cardiomyopathy typically results in dilated cardiomyopathy, with all four cardiac chambers being enlarged. This results in both systolic and diastolic dysfunction. Eventually, heart failure can result, which carries a 50% mortality rate. There is no effective treatment against established cardiomyopathy caused by the drug as of 2010. The drug dexrazoxane may be used to decrease the risk of doxorubicin's cardiotoxicity in certain cases.


title: Doxorubicin

text: Another common and potentially fatal complication of doxorubicin is typhlitis, an acute life-threatening inflammation of the bowel. Additionally, some people may develop PPE, characterized by skin eruptions on the palms of the hand or soles of the feet, swelling, pain, and erythema. Due to these side effects and its red color, doxorubicin has earned the nickname "red devil" or "red death."


title: Doxorubicin

text: Chemotherapy can cause reactivation of hepatitis B, and doxorubicin-containing regimens are no exception.


title: Doxorubicin

text: Doxorubicin and several chemotherapeutic drugs (including cyclophosphamide) can cause a loss of skin pigmentation.


title: Doxorubicin

text: There is a pegylated (polyethylene glycol coated) liposome-encapsulated form of doxorubicin, developed to treat Kaposi's sarcoma The polyethylene glycol coating results in preferential concentration of doxorubicin in the skin. However, this also results in a side effect called palmar plantar erythrodysesthesia (PPE), more commonly known as hand-foot syndrome.


title: Doxorubicin

text: Following administration of this form of doxorubicin, small amounts of the drug can leak from capillaries in the palms of the hands and soles of the feet. The result of this leakage is redness, tenderness, and peeling of the skin that can be uncomfortable and even painful. In clinical testing at 50 mg/m dosing every 4 weeks, half of people developed hand-foot syndrome. The rate of this side effect limits the dose of this formulation that can be given as compared with plain doxorubicin in the same treatment regimen, thereby limiting potential substitution. Substitution would be desirable because liposome-encapsulated doxorubicin is less cardiotoxic than unencapsulated doxorubicin. This liposome-encapsulated form is also approved by the FDA for treatment of ovarian cancer and multiple myeloma.


title: Doxorubicin

text: A non-pegylated liposomal doxorubicin, called Myocet, is approved in the European Union and in Canada for the treatment of metastatic breast cancer in combination with cyclophosphamide, but it has not been approved by the FDA for use in the United States. Unlike Doxil, the Myocet liposome does not have a polyethylene glycol coating, and therefore does not result in the same rate of PPE. The minimization of this side effect may allow for one-for-one (1:1) substitution with doxorubicin in the same treatment regimen, thereby improving safety with no loss of efficacy. Like Doxil, the liposomal encapsulation of the doxorubicin limits the cardiotoxicity. In theory, by limiting the cardiotoxicity of doxorubicin through liposomal encapsulation, it can be used safely in concurrent combination with other cardiotoxic chemotherapy drugs, such as trastuzumab. There is an FDA black box warning that trastuzumab cannot be used in concurrent combination with doxorubicin, only in sequential combination. Though concurrent combination of trastuzumab and doxorubicin in clinical studies found superior tumor response, the combination resulted in unacceptable cardiotoxicity, including risk of cardiac failure manifesting as congestive heart failure (CHF). Published phase II study results have shown that Myocet, trastuzumab, and paclitaxel can safely be used concurrently without the cardiac risk, as measured by reduction in LVEF function, while still achieving superior tumor response. This finding is the basis for the ongoing phase III trial for FDA approval.


title: Doxorubicin

text: Doxorubicin (DXR) is a 14-hydroxylated version of daunorubicin, the immediate precursor of DXR in its biosynthetic pathway.


title: Doxorubicin

text: Daunorubicin is more abundantly found as a natural product because it is produced by a number of different wild type strains of "Streptomyces". In contrast, only one known non-wild type species, "Streptomyces peucetius" subspecies "cesius" ATCC 27952, was initially found to be capable of producing the more widely used doxorubicin. This strain was created by Arcamone et al. in 1969 by mutating a strain producing daunorubicin, but not DXR, at least in detectable quantities. Subsequently, Hutchinson's group showed that under special environmental conditions, or by the introduction of genetic modifications, other strains of "Streptomyces" can produce doxorubicin. His group also cloned many of the genes required for DXR production, although not all of them have been fully characterized. In 1996, Strohl's group discovered, isolated and characterized dox A, the gene encoding the enzyme that converts daunorubicin into DXR.


title: Doxorubicin

text: By 1999, they produced recombinant dox A, a cytochrome P450 oxidase, and found that it catalyzes multiple steps in DXR biosynthesis, including steps leading to daunorubicin. This was significant because it became clear that all daunorubicin-producing strains have the necessary genes to produce DXR, the much more therapeutically important of the two. Hutchinson's group went on to develop methods to improve the yield of DXR, from the fermentation process used in its commercial production, not only by introducing dox A encoding plasmids, but also by introducing mutations to deactivate enzymes that shunt DXR precursors to less useful products, for example baumycin-like glycosides. Some triple mutants, that also over-expressed dox A, were able to double the yield of DXR. This is of more than academic interest, because at that time DXR cost about $1.37 million per kg and current production in 1999 was 225 kg per annum.


title: Doxorubicin

text: More efficient production techniques have brought the price down to $1.1 million per kg for the nonliposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps, and the yield is poor. Since daunorubicin is produced by fermentation, it would be ideal if the bacteria could complete DXR synthesis more effectively.


title: Doxorubicin

text: Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of topoisomerase II, an enzyme which relaxes supercoils in DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being released and thereby stopping the process of replication. It may also increase quinone type free radical production, hence contributing to its cytotoxicity.


title: Doxorubicin

text: The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures.


title: Doxorubicin

text: By intercalation, doxorubicin can also induce histone eviction from transcriptionally active chromatin. As a result, DNA damage response, epigenome and transcriptome are deregulated in doxorubicin-exposed cells.


title: Doxorubicin

text: In the 1950s, an Italian research company, Farmitalia Research Laboratories, began an organized effort to find anticancer compounds from soil-based microbes. A soil sample was isolated from the area surrounding the Castel del Monte, a 13th-century castle. A new strain of "Streptomyces peucetius", which produced a red pigment, was isolated, and an antibiotic from this bacterium was effective against tumors in mice. Since a group of French researchers discovered the same compound at about the same time, the two teams named the compound daunorubicin, combining the name "Dauni", a pre-Roman tribe that occupied the area of Italy where the compound was isolated, with the French word for ruby, "rubis", describing the color. Clinical trials began in the 1960s, and the drug was successful in treating acute leukemia and lymphoma. However, by 1967, it was recognized that daunorubicin could lead to fatal cardiac toxicity.


title: Doxorubicin

text: Researchers at Farmitalia soon discovered that changes in biological activity could be made by minor changes in the structure of the compound. A strain of "Streptomyces" was mutated using "N"-nitroso-"N"-methyl urethane, and this new strain produced a different, red-colored antibiotic. They named this new compound Adriamycin, after the Adriatic Sea, and the name was later changed to doxorubicin to conform to the established naming convention. Doxorubicin showed better activity than daunorubicin against mouse tumors, and especially solid tumors. It also showed a higher therapeutic index, yet the cardiotoxicity remained.


title: Doxorubicin

text: Doxorubicin and daunorubicin together can be thought of as prototype compounds for the anthracyclines. Subsequent research has led to many other anthracycline antibiotics, or analogs, and there are now over 2,000 known analogs of doxorubicin. By 1991, 553 of them had been evaluated in the screening program at the National Cancer Institute (NCI). In 2016 GPX-150 was granted orphan drug designation by US FDA.


title: Doxorubicin

text: On 24 March 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Zolsketil pegylated liposomal, intended for the treatment of metastatic breast cancer, advanced ovarian cancer, progressive multiple myeloma and AIDS-related Kaposi's sarcoma. The applicant for this medicinal product is Accord Healthcare S.L.U. Zolsketil pegylated liposomal is a hybrid medicine of Adriamycin. It contains the same active substance as Adriamycin, but is available in a pegylated liposomal formulation. Zolsketil pegylated liposomal was approved for medical use in the European Union in May 2022.


title: Doxorubicin

text: On 21 July 2022, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Celdoxome pegylated liposomal, intended for the treatment of metastatic breast cancer, advanced ovarian cancer, progressive multiple myeloma and AIDS-related Kaposi's sarcoma. The applicant for this medicinal product is YES Pharmaceutical Development Services GmbH. Celdoxome pegylated liposomal is a hybrid medicine of Adriamycin which has been authorized in the EU since 24 October 1979. Celdoxome pegylated liposomal contains the same active substance as Adriamycin, but is available in a pegylated liposomal formulation.


title: Doxorubicin

text: It is sold under a number of different brand names, including Adriamycin PFS, Adriamycin RDF, or Rubex.


title: Doxorubicin

text: Doxorubicin is photosensitive, and containers are often covered by an aluminum bag and/or brown wax paper to prevent light from affecting it. Doxorubicin is also available in liposome-encapsulated forms as Doxil (pegylated form), Myocet (nonpegylated form), and Caelyx, which are also given by intravenous injection.


title: Doxorubicin

text: Combination therapy experiments with sirolimus (rapamycin) and doxorubicin have shown promise in treating Akt-positive lymphomas in mice.


title: Doxorubicin

text: Further, the release of photo-activated adriamycin with the aid of nanoporous optical antenna resulted in significant anti-cancer effect in MCF-7 breast cancer cells.


title: Doxorubicin

text: In 2006, animal research coupling a murine monoclonal antibody with doxorubicin created an immunoconjugate that was able to eliminate HIV-1 infection in mice.


title: Doxorubicin

text: There is some evidence for antimalarial activity for doxorubicin and similar compounds. In 2009, a compound similar in structure to doxorubicin was found to inhibit plasmepsin II, an enzyme unique to the malarial parasite "Plasmodium falciparum". The pharmaceutical company GlaxoSmithKline (GSK) later identified doxorubicin in a set of compounds that inhibit parasite growth


title: Doxorubicin

text: Doxorubicin is also known to be fluorescent. This has often been used to characterize doxorubicin concentrations, and has opened the possibility of using the molecule as a theranostic agent. However, there are significant limitations, as doxorubicin's fluorescence spectrum is known to depend on a variety of factors, including the pH of the environment, solvent dielectric constant and others. Doxorubicin fluorescence is quenched by binding to DNA, and shielded by micelle encapsulation. It is also known to self-quench at high concentrations. In contrast, histone binding amplifies fluorescence.


title: Opel Kadett

text: The Opel Kadett is a small family car produced by the German automobile manufacturer Opel from 1936 until 1940 and then from 1962 until 1991 (the Cabrio continued until 1993), when it was succeeded by the Opel Astra.


title: Opel Kadett

text: The first Opel car to carry the Kadett name was presented to the public in December 1936 by Opel's Commercial-Technical director, Heinrich Nordhoff, who would in later decades become known for his leadership role in building up the Volkswagen company.


title: Opel Kadett

text: The new Kadett followed the innovative Opel Olympia in adopting a chassis-less unibody construction, suggesting that like the Vauxhall 10 introduced in 1937 by Opel's English sister-company, the Opel Kadett was designed for high volume low-cost production.


title: Opel Kadett

text: For 1937 the Kadett was offered as a small and unpretentious two door "Limousine" (sedan/saloon) or, at the same list price of , as a soft top "Cabrio-Limousine". The body resembled that of the existing larger Opel Olympia and its silhouette reflected the "streamlining" tendencies of the time. The 1,074 cc side-valve engine came from the 1935 Opel P4 and came with the same listed maximum power output of at 3,400 rpm. The wheelbase, at , was right between the little P4 and the larger Olympia. The "11234" nomenclature stands for the engine's displacement in deciliters (11) followed by the wheelbase in centimeters (234).


title: Opel Kadett

text: The brakes were now controlled using a hydraulic mechanism. The suspension featured , a suspension configuration already seen on the manufacturer's larger models and based on the Dubonnet system for which General Motors in France had purchased the license. The General Motors version, which had been further developed by Opel's North American parent, was intended to provide a soft ride, but there was some criticism that handling and road-holding were compromised, especially when the system was applied to small light-weight cars such as the Kadett. By the end of 1937 33,402 of these first-generation Kadetts had been produced.


title: Opel Kadett

text: From December 1937 a modified front grill identified an upgrade. The 1,074cc Opel engine and the wheelbase were unchanged, with few differences between the cars for 1937 and those for 1938.


title: Opel Kadett

text: The manufacturer now offered two versions of the Kadett, designated the "Kadett KJ38 and the "Kadett K38" the latter also being sold as the "Kadett Spezial". Mechanically and in terms of published performance there was little to differentiate the two, but the "Spezial" had a chrome stripe below the window line and extra external body trim in other areas such as on the front grill. The interior of the "Spezial" was also better equipped. To the extent that the 300 Mark saving for buyers of the car reflected reduced production costs, the major difference was that the more basic "KJ38" lost the with which the car had been launched, and which continued to be fitted on the "Spezial". The base car instead reverted to traditional rigid axle based suspension similar to that fitted on the old Opel P4.


title: Opel Kadett

text: The base car was available only as a two-door "Limousine" (sedan/saloon). Customers looking for a soft-top "Cabrio-limousine" would need to specify a "Kadett Spezial". For the first time Kadett buyers, provided they were prepared to choose a "Kadett Spezial" could also specify a four-door "Limousine" (sedan/saloon) bodied car, priced at as against for a "Spezial Cabrio-Limousine" and for a two-door "Spezial Limousine".


title: Opel Kadett

text: The "Kadett KJ38" was intended to fill the market segment of the Opel P4, but the KJ38, priced at , was more expensive than the P4 and its reduced specification left it with the image of a car for poor people ("..Image des Arme-Leute-Autos..") at a time when economic growth in Germany was finally fostering a less minimalist approach to car buying. The "Kadett K38 Spezial" fared better in the market place: in 1938 and again in 1939 it was Germany's top-selling small car. By May 1941 the company had produced 17,871 "Kadett KJ38"s and 56,335 "Kadett K38 Spezial"s.


title: Opel Kadett

text: Competitive pricing led to commercial success, and Kadetts continued to be produced during the early months of the war: by the time production ended in May 1940, following the intensification of World War II, 106,608 of these Opel Kadetts were produced on the assembly line at Opel's Rüsselsheim plant, which had been the first major car plant in Germany to apply the assembly-line techniques pioneered by Henry Ford.


title: Opel Kadett

text: After the Second World War the Soviet Union requested the tooling from the Opel Rüsselsheim car plant in the American occupation zone as part of the war reparations agreed by the victorious powers, to compensate for the loss of the production lines for the domestic KIM-10-52 in the siege of Moscow. Faced with a wide range of German "small litrage" models to choose from, Soviet planners wanted a car that closely followed the general type of the KIM – a 4-door sedan with an all-metal body and 4-stroke engine. They, therefore, rejected both the rear-engined, two-door KdF-Wagen (future VW Beetle) and the two-stroke powered, front-wheel-drive, wooden-bodied DKW F8, built by the Auto Union Chemnitz plant in the Soviet occupation zone. The closest analog of the KIM to be found was the 4-door Kadett K38.


title: Opel Kadett

text: On 26 August 1945, the State Defense Committee published Order No. 9905, which prescribed the start of production of the 4-door Kadett on the Moscow small car plant "without any changes to the design". The implementation of the plan was far from smooth. The Rüsselsheim plant had been deeply involved in the Nazi war effort, producing aircraft engines for the Luftwaffe, and consequently has been heavily damaged by the Allied air raids. Very little was left to be salvaged – mostly incoherent drawings and plans, with several stamping dies for the 2-door version of the Kadett to add.


title: Opel Kadett

text: Still, a number of Kadetts had been captured as trophies by the Red Army and were available for study and reverse-engineering. This project was conducted by design bureaus formed as Soviet-German joint ventures under the Soviet Military Administration in Germany (SMAD). There were 11 of them in total. One in Berlin reverse-engineered the engine and transmission. Another in Schwarzenberg worked on the steel body. The wooden-bodied station wagon was developed in Chemnitz. The vast majority of the personnel of these design bureaus were German specialists and craftsmen hired by the Military Administration. These design bureaus not only prepared the necessary blueprints and documentation, but also provided the wooden master model for the body. They even developed the new trim pieces which distinguished the Moskvitch from its Opel prototype, including hood emblems and hubcaps with a large "M" (for "Moskvitch"). However, the stamping dies and most of the tooling had to be produced in the USSR.


title: Opel Kadett

text: Production started on 4 December 1946. The Moskvitch 400/420 continued to be made in Moscow with some minor changes until 1956, when it was replaced by the Moskvitch 402. The latter was an all-new design apart from the engine, for which Moskvitch continued to use the Kadett side-valve engine until 1958, when it was replaced with a domestically designed OHV engine.


title: Opel Kadett

text: The Kadett was reintroduced in 1962, with deliveries beginning on 2 October, a little more than 22 years after the original model was discontinued in May 1940. The new car (designated the Kadett A) was a small family car like its predecessor, although it was now available in 2-door saloon, 3-door estate ("Car-A-Van") and coupé versions.


title: Opel Kadett

text: The Kadett B was launched at the Frankfurt Motor Show in late summer 1965, The Kadett B was larger all-round than the Kadett A: 5% longer both overall and in terms of the wheelbase, 7% wider and 9% heavier (unladen weight), albeit lower in basic standard "Limousine" (sedan/saloon) form. Production ended in July 1973, with the successor model introduced a month later following the summer shut-down, in August. The two-seat Opel GT was heavily based on Kadett B components, its body made by a French contractor, Brissonneau & Lotz, at their Creil factory.


title: Opel Kadett

text: The Kadett C appeared in August 1973 and was Opel's version of the General Motors' "T-Car". It was the last small Opel to feature rear-wheel drive, and remained in production at Opel's Bochum plant until July 1979, by which time Opel had produced 1,701,076. Of these, 52% had been exported outside West Germany, most of them to markets in other parts of western Europe.


title: Opel Kadett

text: The Kadett C was mirrored in Europe by its British derivative - the Vauxhall Chevette. For the first time the Opel Kadett and its Vauxhall equivalent were now very clearly the same car, and marked the gradual convergence of Opel and Vauxhall models, which would be completed with the later Kadett D.


title: Opel Kadett

text: The Kadett D was introduced in the middle of August 1979, with deliveries on the home market beginning early in September 1979. In November 1979, the car went on sale in the United Kingdom, some five months before the Vauxhall Astra Mark 1, the British version, was launched in April 1980. The cars were designed as three- or five-door hatchbacks and estates or station wagons. There were also two- and four-door sedans featuring separate boots/trunks, which shared the silhouettes of the hatchbacks: in the United Kingdom, the sedan versions were soon withdrawn, until the 1986 launch of the MKII-based Belmont. For the first time since 1965, there was no coupé-bodied Kadett in the range: the previous Kadett C coupé was indirectly replaced by the three-door 1.3 SR sports model.


title: Opel Kadett

text: Technologically, the Kadett D was part of a major investment for Opel (and General Motors as a whole) in a new front-wheel drive architecture, with an all-new family of engines and transmissions which would later be applied in the larger Ascona C and the smaller Corsa A in 1981, and 1982, respectively. It was also the first application of the Family II engine design, with a single overhead camshaft, aluminium-alloy cylinder head, hydraulic valve lifters, with capacities of 1297 cc (producing 60 PS and 75 PS) and had a transaxle design that allowed the clutch to be replaced without removing the transmission unit. A carry-over 1196 cc Opel OHV engine from previous generations of the Kadett producing and a top speed of was also offered on entry level models from launch, and a new 1600 cc engine was offered after Frankfurt 1981, followed by an 1800 cc version introduced for the Kadett GSE/Astra GTE model. The Kadett D was also equipped with a 1600 cc diesel engine, an option which was first presented at the Brussels Motor Show in 1982. Another frugal model, mostly sold in Italy, was the 1.0 liter model with .


title: Opel Kadett

text: This range of engines was also used for later models of the Corsa/Nova, and the mid-sized Cavalier/Ascona. From May 1981, the 1.3 was also available with a three-speed automatic. The automatic was made available to the diesel in September 1982. In the United Kingdom, Opels and Vauxhalls were initially sold through separate marketing operations, with overlapping lineups that competed directly with each other. By 1982 this anomaly had been sorted out and the Opel lineup was limited to the well-equipped five-door Berlina (1.3S or 1.6S) and the sporty 1.6 SR, leaving most of the market to the Vauxhall-badged cars.


title: Opel Kadett

text: One interesting version which first appeared in mid-1982 was the Kadett Pirsch, (for deer stalking, a stealthy form of hunting). In non-German-speaking countries it was generally marketed as the "Kadett Off Road." This was a station wagon with rustic trim, fitted with a limited-slip differential, reinforced suspension and more suitable tires, increased ground clearance, a skid plate, and shortened front fenders. In Sweden, a special postal Kadett ("Opel Kadett Post") was offered, fitted with a high roof (necessitating a unique and much taller windshield) and a sliding right-hand door, RHD, and the automatic transmission. This version was converted by in Würzburg, Germany. Voll also made a postal version of the later Kadett E.


title: Opel Kadett

text: The Kadett D was also sold as the IDA Kadett and assembled Kikinda, Yugoslavia. In Indonesia, PT. Garmak Motor was also reproduced Kadett D after 1984 in Jakarta, only for local market general buyers and taxi fleets until around 1995. It was later replaced by Opel Optima (Astra F) sedan. Only available as a 5-door hatchback, with carburetted 1298 cc GM Family 1 engine and 5-speed manual transmission.


title: Opel Kadett

text: The Opel Kadett D was also built in South Africa by General Motors South African (Pty) Ltd. The South African range was made up of four-door fastback sedans, five-door hatchbacks, and a five-door estate model called the Voyage. The engines used are Opel's 1.2-litre overhead valve inline-four (L models only), or the OHC 1.3-litre (GL, GLS, and Voyage). Power is and respectively. Later a 1.6 L was added and also a 1.8 L in the GTE performance model.


title: Opel Kadett

text: Small engine sizes with round lights on the bonnet while large engine sizes would have square lights on the bonnet.


title: Opel Kadett

text: The Kadett E (Vauxhall Astra Mark 2 in the United Kingdom) was introduced in August 1984, and was voted the 1985 European Car of the Year. The 1984 model was also developed into a more conventional three-box design with a boot (trunk), badged as the Vauxhall Belmont in the United Kingdom, launched at Frankfurt 1985. This was awarded the 1985 Semperit Irish Car of the Year in Ireland. There was a station wagon called the "Caravan", available with either three or five doors. In South Africa, the Kadett notchback was sold as the Opel Monza, along with a convertible. This replaced the Opel Ascona.


title: Opel Kadett

text: The car was noted for its advanced aerodynamics and distinctive "teardrop" shape - mirroring the trend in the mid 1980s for swooping aerodynamic styling - with the front end styling taken directly from the Opel Tech 1 concept car of 1981, although some styling cues from the Kadett D were retained for continuity such as its 'Kamm tail' and oversized C-pillar extraction vent.


title: Opel Kadett

text: A convertible version was also available, for the first time in 1987, built by Bertone of Torino, Italy, bringing it to line with competitors, such as the Ford Escort and Volkswagen Golf. For the 1988 model, capacities were raised from 1.3 to 1.4 litres. In the fall of 1986 a new 1,998 cc engine replaced the 1.8 hitherto used on the GSi and Vauxhall Astra GTE in many markets, although the 1.8 continued to be sold in some places. In 1988, a 16-valve twin-cam version was developed for a high-performance GSi/GTE model, yielding in non-catalyzed form, six less horsepower with a catalytic converter fitted. While criticized for a lack of refinement, the GSi 16V was also lauded as the most powerful car available in its class at the time. Aside from the "16V" badging, it could be told from an eight-valve GSi by its twin rectangular exhaust pipes.


title: Opel Kadett

text: The Kadett E was a grey import in the United Kingdom, but not popular compared to its badge engineered sister, the Vauxhall Astra Mk II. It was never officially sold in Britain, and by 1989, General Motors was only marketing the Vauxhall brand in the United Kingdom, although Astras assembled at Vauxhall's Ellesmere Port plant were exported to the rest of Europe badged as Opel Kadetts. There was also a van version with a raised roof, called the Opel Kadett Combo in Europe, and the Bedford Astramax in the United Kingdom.


title: Opel Kadett

text: In Brazil, the Kadett E succeeded some versions of the Chevrolet Chevette and was introduced as the Chevrolet Kadett, with the station wagon version called the Chevrolet Ipanema. The latter had three doors until model year 1993, when five doors became mandatory. The hatchback was only available with three doors, and the sedan was never offered. Brazilian production of the hatchback commenced in April 1989, with the Ipanema being added in October. From 1995 all versions featured fuel injection. Brazilian cars received either 1.8 or 2.0 L petrol or ethanol fours. The Ipanema was discontinued in 1996, and the Kadett, in 1998.


title: Opel Kadett

text: While the Ipanema clearly succeeded the Marajó, production of the Chevette (by now in sedan form only, the hatchback having been discontinued after the 1987 model year) and of the Kadett noticeably overlapped; the newer model was placed above the old one in Chevrolet's lineup. While Chevrolet entertained the possibility of a pick-up version of the Kadett E, it never materialized.


title: Opel Kadett

text: A convertible version of the Kadett was also offered in Brazil. It was made available between 1991 and 1994, its body was sent to the Bertone factory in Italy and finished in Brazil. It was only available with the 2.0-litre multi-point electronic injection engine with 121 ps / 120 hp.


title: Opel Kadett

text: In the early 1990s, South African Kadett GSi's were further upgraded based on their success in production car racing and initially 500 special units were built as road cars for homologation purposes. This was a minimum requirement for entry into the Stannic Group N races. They went against BMW's 325iS (A 2.7 L homologation special from BMW). They featured more aggressive 276-degree camshafts made by Schrick with 2 different settings for timing overlap (110° and 107°), revised intake and exhaust modifications (4-in-1 branch manifold and freeflow exhaust), Irmscher spring kit, modified engine management system by Promotec, a limited-slip differential developed by Andre Verwey and special Aluett 7Jx15-inch ET35 alloy wheels, they were nicknamed the "Superboss" and held the world record for the most torque per litre (114 Nm per litre) for a naturally aspirated car until being beaten by the Ferrari 458 (117 Nm per litre) in 2009. After the required 500 units were produced, many more were built to satisfy public demand.


title: Opel Kadett

text: The Kadett E formed the basis of the Daewoo LeMans (later known as the Daewoo Cielo, and Nexia) in South Korea, Nexia being the hatchback version), which was sold in the United States and New Zealand as the Pontiac LeMans, and in Canada (initially) as the Passport Optima. LeMans sales ended in 1993. The Nexia was produced until 2016 at the UzDaewoo plant in Asaka, Uzbekistan. The Cielo was last being produced at Automobile Craiova, a semi-independent (from GM) plant in Craiova, Romania. Their license expired in the fall of 2006, and Cielo was produced until 2007.


title: Opel Kadett

text: In 1991, GM Europe decided to standardise model names across its two brands, and Opel adopted Vauxhall's name for the Kadett, Astra, for the replacement car for Europe which debuted that year. Only South Africa kept the Kadett name until the 1999 (Astra/Kadett F), whereafter all models took the Astra name.


title: Opel Kadett

text: However, under Opel's internal naming convention, successive generations of the Astra platform are treated as a logical continuation of the Kadett lineage, hence the original 1991 Astra was designated "Astra F" in relation to the previous Kadett E. This convention has continued through the current Astra L.


title: Felix Mallard

text: Felix Mallard (born 20 April 1998) is an Australian actor, musician, and model. His career began in 2014, playing Ben Kirk in the Australian television soap opera "Neighbours". Mallard moved to the United States in 2018 and starred in the American comedy series "Happy Together" as Cooper, until its cancellation in 2019. He plays Lucas Caravaggio in the Netflix series "Locke & Key", Aiden in "Zoey's Extraordinary Playlist", and Marcus Baker in "Ginny & Georgia."


title: Felix Mallard

text: Mallard grew up in Melbourne, Australia. He has a sister named Tiana He attended the all-boys school Christian Brothers College, where he was a College Prefect. He completed the Victorian Certificate of Education (VCE) in 2015, as well as a course in Technical Production. Mallard took up fencing at the age of ten. He competed at state and national levels, winning two bronze medals in the team events at the 2012 Victorian National Champions and 5th place in the under-15 National Sabre Championships in 2013. When he was 13, Mallard was scouted by a modelling agent and signed with Vivien's Models. He featured in several campaigns, including an editorial spread in Yves Magazine. Mallard is a musician and plays the guitar, piano and drums. He is a guitarist and singer in punk rock band Enemies Alike. The band has played in venues around Melbourne, at school music events, and Associated Catholic Colleges' Battle of the Bands competitions.


title: Felix Mallard

text: Mallard made his acting debut in 2014 at the age of 15, taking over the role of Ben Kirk in the Australian television soap opera "Neighbours" for a three-week, six episode guest stint. He obtained an audition through his modelling agent, which he unexpectedly won. He had never previously considered acting but this experience made him realise this was what he wanted to do for the rest of his life. He returned the following year for a further 4-month guest stint, while still at school. After finishing Year 12, Mallard chose to pursue acting full-time and he re-joined "Neighbours" as a permanent cast member in 2016. Mallard's interest in music was incorporated into his character and he frequently played music on the show. That same year, he starred in "Xanthe ♥ Ben", a 20-episode online spin-off released on Instagram, as well as the webisode series "Summer Stories", broadcast during the 2016 Christmas period. Mallard filmed his final scenes for "Neighbours" in late 2017. His final storyline as Ben saw him move to his late father's home town of Oakey, Queensland to start over. His final episode aired on 10 April 2018. He made two return appearances by video link, airing on 31 December 2018 and 7 January 2019. He also featured in the music video of Melbourne band Maefire's "Without You" in 2016.


title: Felix Mallard

text: Following his departure from "Neighbours", Mallard starred in his former co-star Travis Burns's short film "Money Is Just a Barbell," which he also produced and did the music. He moved to the United States at the start of 2018 and quickly secured the role of popstar Cooper James in the CBS comedy series "Happy Together", alongside Damon Wayans Jr. and Amber Stevens West. "Happy Together" is loosely based on the experiences of English singer Harry Styles, who moved in with television producer Ben Winston and his family to escape the spotlight when the pop band One Direction exploded in popularity. After being offered the role by the television show's producer Winston, Mallard received telephone calls from Harry Styles and James Corden, who convinced him to accept the role. Mallard initially auditioned with an American accent, but was asked to switch to his native Australian accent. The show debuted on 1 October 2018, but after mediocre ratings, it was announced on 28 November 2018, that CBS had declined to order additional episodes of the series beyond the initial order of thirteen. CBS cancelled the show on 10 May 2019.


title: Felix Mallard

text: Mallard went on to play the recurring role of Lucas Caravaggio in the Netflix horror series "Locke & Key:" a 17-year old friend of Rendell Locke, who died 25 years earlier, after being possessed by a demon. Filming took place in the first half of 2019. It was released on 7 February 2020. He appeared in the romantic drama film "All the Bright Places", which began filming in October 2018 and was also released by Netflix in February 2020. The film is an adaptation of Jennifer Niven's 2015 young adult novel of the same name.


title: Felix Mallard

text: In 2021, Mallard began a recurring role in the second season of the musical comedy-drama series "Zoey's Extraordinary Playlist" on NBC, as Zoey's neighbour – an Australian musician, who recently graduated college and has returned from backpacking in Thailand. The role included performing a number of songs and dancing.


title: Felix Mallard

text: Mallard plays series regular Marcus, an edgy 15 year old, in the Netflix dramedy "Ginny & Georgia". Mallard was required to learn American Sign Language for the role, as his character's father is deaf. Filming took place in Toronto during the second half of 2019 and the series was released on 24 February 2021. "Ginny & Georgia" was renewed for a second season, after season one was watched by 52 million viewers within 28 days, making it Netflix's tenth most watched series. It is expected to air in mid-late 2022. The popularity of the show saw Mallard's following on Instagram increase from 90,000 to over 3 million, after its release.


title: Nivea

text: Nivea (, stylized as NIVEA) is a German personal care brand that specializes in skin and body care. It is owned by the Hamburg-based company Beiersdorf Global AG. The company was founded on 28 March 1882, by Paul Carl Beiersdorf. In 1890, it was sold to Oscar Troplowitz. Troplowitz working with Beiersdorf's associate, Paul Gerson Unna, and the German chemist Isaac Lifschütz, developed a new skin care cream. In 1900, Lifschütz developed the first stable water-in-oil emulsion, Eucerit. This was the origin of Eucerin. "Nivea" comes from the Latin adjective "niveus", "nivea", "niveum", meaning "snow-white".


title: Nivea

text: During the 1930s, Beiersdorf produced various products such as tanning oils, shaving creams, shampoo, facial cleanser, and toners. In World War II, the trademark "NIVEA" was expropriated in many countries. After the war, Beiersdorf bought the rights back. During the 1980s, the NIVEA brand expanded into a wider global market.


title: Nivea

text: Paul Carl Beiersdorf established the company on 28 March 1882. The date of the patent document for the manufacture of medical plasters is taken as the date of the company’s formation. Beiersdorf produced gutta-percha plasters in his laboratory on the basis of his patent, laying the foundations for modern plaster technology. In 1890, pharmacist Oskar Troplowitz took over the company.


title: Nivea

text: The company signed its first international cooperation agreement in 1893, with U.S. trading company Lehn & Fink.


title: Nivea

text: Professional wound care was spun off in line with the new strategy and contributed to a joint venture between Beiersdorf and Smith & Nephew. BSN medical, domiciled in Hamburg, was founded.


title: Nivea

text: In 2011, NIVEA was fined $900,000 by the U.S. Federal Trade Commission for falsely claiming that consumers could slim down by regularly applying NIVEA My Silhouette! cream to their skin. The same year, NIVEA published a world map on its website that omitted Israel; Simon Wiesenthal Center protests.


title: Nivea

text: In June, 2019, marketing and media industry journal Ad Age reported on June 26, 2019 that FCB, Nivea’s long-time ad agency, had ended its relationship with the company. Among the primary reasons cited was NIVEA's rejection of a proposed ad that featured two men's hands touching because, according to a NIVEA executive, “we don't do gay at NIVEA.” Crain's Chicago Business reported that FCB had ended the relationship of more than a century. Noting that the breakup occurred at the end of Gay pride month, Crain's noted that FCB would be forgoing the management of NIVEA's $21.8 million U.S. advertising budget. It represented 1% of FCB's revenue globally.


title: Henry V (1989 film)

text: Henry V is a 1989 British historical drama film adapted for the screen and directed by Kenneth Branagh, based on William Shakespeare's play of the same name about King Henry V of England. The film stars Branagh in the title role with Paul Scofield, Derek Jacobi, Ian Holm, Emma Thompson, Alec McCowen, Judi Dench, Robbie Coltrane, Brian Blessed, and Christian Bale in supporting roles.