title: Cliff Williams

text: In 1972, Jim Anderson replaced John on keyboards and Home released a self-titled album, featuring their only hit single, "Dreamer", which peaked at No. 41 in the UK album charts. Their next album, "The Alchemist", followed in 1973, but did not gain chart success. When British folk singer-songwriter Al Stewart suggested that Home back him on his first American tour in March 1974, Mick Stubbs left the group. The rest of the members became the Al Stewart Band, but split up after the tour. Williams briefly played with the American band Stars before forming Bandit in 1974. Bandit's line-up included vocalist Jim Diamond and drummer Graham Broad (later in Bucks Fizz and Roger Waters's band). The group signed with Arista Records and released a self-titled album in 1977. Bandit also performed as Alexis Korner's backing band on 1977's "The Lost Album" before disbanding later that year.


title: Cliff Williams

text: Williams considered retiring from music following Bandit's breakup, but one of the group's guitarists, Jimmy Litherland, convinced him to audition for the Australian group AC/DC, who were looking for a bassist after firing Mark Evans shortly after recording their 1977 studio album "Let There Be Rock". AC/DC had formed in Australia in 1973 and by mid-1977 the line-up was Malcolm Young on rhythm guitar and backing vocals alongside his brother Angus Young on lead guitar, Phil Rudd on drums and Bon Scott on vocals. Shortly after deciding to audition for the band, Williams saw AC/DC on "Top of the Pops" and was impressed, describing them as "outrageous".


title: Cliff Williams

text: For his audition, Williams played four jam sessions with the band, and on 27 May 1977 was officially asked to join AC/DC. Angus declared the decision was partially motivated by the bassist's good looks, which the band hoped would attract more women to their concerts. As Williams was replacing an Australian musician, there were issues resulting in problems obtaining a work permit to enter the country. His first performances with AC/DC were in Australia supporting the "Let There Be Rock" album, with two secret gigs at Sydney's Lifesaver. The album "Powerage" (1978), produced by Vanda & Young, marked Williams's studio debut. Williams remained in AC/DC from that time onwards until 2016, with only a temporary departure in 1991 as he suffered a kidney infection, during which Paul Greg had to play bass for some North American concerts in the Razors Edge World Tour. In addition to his role as bassist with AC/DC, Williams also contributed backing vocals. He has said that his favourite albums with the band are "Powerage" and "Back in Black". On 7 July 2016, Williams announced his plans to retire from the music industry following AC/DC's Rock or Bust World Tour. He cited his opinion that AC/DC was now "a changed animal" with the recent departures of several core band members; Malcolm Young could no longer contribute due to dementia, Phil Rudd could not tour due to being under house arrest, and Brian Johnson was forced into retirement due to hearing problems. In September 2016, during his last performance with AC/DC at the Wells Fargo Center in Philadelphia, Williams was brought to the front of the stage by Angus Young to take a bow in the middle of "For Those About to Rock (We Salute You)". On September 30, 2020, AC/DC officially confirmed that Williams, along with fellow band mates Brian Johnson and Phil Rudd, have rejoined the band.


title: Cliff Williams

text: In 1984, Williams played bass and backing vocals on Adam Bomb's song "I Want My Heavy Metal", for the album "Fatal Attraction". During AC/DC's hiatus in the 2000s, Williams joined Bosnian musician Emir Bukovica's band Emir & Frozen Camels. The group recorded the album "San" in 2002 and played in some European clubs. In 2005, Williams and AC/DC singer Johnson played in a hurricane relief event in Florida, promoted by the John Entwistle Foundation. There Williams met drummer Steve Luongo, president of the foundation and former member of the John Entwistle band. Luongo later brought Williams, Johnson, and guitarist Mark Hitt for the Classic Rock Cares charity project. The quartet composed and recorded ten tracks in the studio in 2007, and followed that with a tour to raise funds for the foundation. In 2011, Williams played on a benefit concert organized by Mark Farner. Williams said he also occasionally plays with a rhythm and blues band from Fort Myers called The Juice.


title: Cliff Williams

text: Since Williams' introduction to the band, AC/DC has been inducted to the Australian Recording Industry Association's Hall of Fame (in 1988), and the Rock and Roll Hall of Fame (in 2003). In 1982, Williams was chosen as "Bassist of the Year" in a vote conducted by "Kerrang!" magazine.


title: Cliff Williams

text: Williams married his American wife Georganne in 1980. They have two children: model and actress Erin Lucas (born 1984) and Luke (born 1986). The couple initially settled in Hawaii, US, but this left them feeling too isolated, and they found the school system to be lacking. In 1986, they moved to Fort Myers, Florida, US, at the suggestion of AC/DC bandmate and nearby resident Brian Johnson. Williams also spends time in Aix-en-Provence, France, where he has distant relatives. Williams' hobbies include fishing, flying, and wine.


title: Cliff Williams

text: Williams' role in AC/DC was to provide steady but basic basslines which followed the rhythm guitar of Malcolm Young, consisting mostly of eighth notes. His basslines were sometimes written by Malcolm and Angus Young during composition, and at other times Williams developed them based on the other instrumental tracks. Williams has said of his playing, "It's not the [bass] line that counts. It is the "feel". My favorite AC/DC tune to play is 'Down Payment Blues', because it's so simple. I play four notes throughout the song, but I get off on the "whole" thing—not me noodlin' away." He also said that he plays "the same thing in every song, for the most part [...] in AC/DC's music, the song is more important than any individual's bit in it". He added that "complex [bass] lines wouldn't add anything to a guitar-oriented band like [AC/DC], so [he tries] to create a bottom layer that drives what [AC/DC's] guys are doing on top". Williams had no difficulty keeping his low profile within the band, declaring, "I don't have any problem doing this, because I enjoy playing simply. I never feel angry or prisoner." Nevertheless, he very occasionally employs more melodic lines and passing notes on some songs, such as Satellite Blues. His playing technique is mostly centred around downpicking, with the occasional use of plucking to mute the strings, which he says "adds more definition and tightens up the notes, and it gives the sound less sustain".


title: Cliff Williams

text: In his first appearance in 1977, he used a Gibson Ripper only for the "Let There Be Rock" music video. Williams' trademark instrument is the StingRay and other basses by Music Man, strung with D'Addario (.045, .065, .085, .105) flatwounds in the studio and roundwound XLs in concert. In October 2020, Ernie Ball Music Man announced that they are releasing a Cliff Williams Signature Bass which will be a genuine replica of his 1979 Music Man StingRay bass. Williams states that despite trying other basses over the years, he always went back to Music Man's instruments, which he described as "a tremendous work horse of a bass". Other basses used include the Fender Precision Bass, a Gibson Thunderbird non-reverse, Fender Jazz Bass, the Steinberger L-series, a Gibson EB-3 and at least two LAG Custom basses. Williams used 3 Ampeg SVT-810E cabinets with 2 SVT-4PRO Heads, but if there was any interference with the wireless systems, he used cables in his live performances.


title: Whitehall

text: Whitehall is a road and area in the City of Westminster, Central London. The road forms the first part of the A3212 road from Trafalgar Square to Chelsea. It is the main thoroughfare running south from Trafalgar Square towards Parliament Square. The street is recognised as the centre of the Government of the United Kingdom and is lined with numerous departments and ministries, including the Ministry of Defence, Horse Guards and the Cabinet Office. Consequently, the name "Whitehall" is used as a metonym for the British civil service and government, and as the geographic name for the surrounding area.


title: Whitehall

text: The name was taken from the Palace of Whitehall that was the residence of Kings Henry VIII through to William III, before its destruction by fire in 1698; only the Banqueting House has survived. Whitehall was originally a wide road that led to the front of the palace; the route to the south was widened in the 18th century following the destruction of the palace.


title: Whitehall

text: As well as government buildings, the street is known for its memorial statues and monuments, including the UK's primary war memorial, the Cenotaph. South of the Cenotaph the thoroughfare becomes "Parliament Street." The Whitehall Theatre (now the Trafalgar Studios) was formerly associated with a series of farces.


title: Whitehall

text: The name Whitehall was used for several buildings in the Tudor period. It either referred to a building made of light stone, or as a general term for any festival building. This included the Royal Palace of Whitehall, which in turn gave its name to the street.


title: Whitehall

text: The street is about long and runs through the City of Westminster. It is part of the A3212, a main road in Central London that leads towards Chelsea via the Houses of Parliament and Vauxhall Bridge. It runs south from Trafalgar Square, past numerous government buildings, including the old War Office building, Horse Guards, the Ministry of Defence, the Cabinet Office and the Department of Health. It ends at the Cenotaph, the road ahead being Parliament Street. Great Scotland Yard and Horse Guards Avenue branch off to the east, while Downing Street branches off to the west at the southern section of the street.


title: Whitehall

text: The nearest tube stations are Charing Cross at the north end, and Westminster at the south. Numerous London bus routes run along Whitehall, including 12, 24, 88, 159 and 453.


title: Whitehall

text: There has been a route connecting Charing Cross to Westminster since the Middle Ages; the 12th-century historian William Fitzstephen described it as "a continued suburb, mingled with large and beautiful gardens, and orchards belonging to the citizens". The name Whitehall was originally only used for the section of road between Charing Cross and Holbein Gate; beyond this it was known as The Street as far as King Street Gate, then King Street thereafter. It had become a residential street by the 16th century, and had become a popular place to live by the 17th, with residents including Lord Howard of Effingham and Edmund Spenser.


title: Whitehall

text: The Palace of Whitehall, to the east of the road, was originally named York Palace, but was renamed during the reign of Henry VIII. The palace was redesigned in 1531–32 and became the King's main residence later in the decade. He married Anne Boleyn here in 1533, followed by Jane Seymour in 1536, and died at the palace in 1547. Charles I owned an extensive art collection at the palace and several of William Shakespeare's plays had their first performances here. It ceased to be a royal residence after 1689, when William III moved to Kensington Palace. The palace was damaged by fire in 1691, following which the front entrance was redesigned by Sir Christopher Wren. In 1698, most of the palace burned to the ground accidentally after a fire started by a careless washerwoman.


title: Whitehall

text: Wallingford House was constructed in 1572 by William Knollys, 1st Earl of Banbury along the western edge of Whitehall. It was subsequently used by Charles I. During the reign of William III, it was bought for the Admiralty. The Old Admiralty Buildings now sit on the house's site.


title: Whitehall

text: Banqueting House was built as an extension to the Palace of Whitehall in 1622 by Inigo Jones. It is the only surviving portion of the palace after it was burned down, and was the first Renaissance building in London. It later became a museum to the Royal United Services Institute and has been opened to the public since 1963.


title: Whitehall

text: Oliver Cromwell moved to the street in 1647, taking up residence in Wallingford House. Two years later, Charles I was carried through Whitehall on the way to his trial at Westminster Hall. Whitehall itself was a wide street and had sufficient space for a scaffold to be erected for the King's execution at Banqueting House. He made a brief speech there before being beheaded. Cromwell died at the Palace of Whitehall in 1658.


title: Whitehall

text: During the Great Plague of London in 1665, people boarded coaches at Whitehall, then at the edge of urban London, in an attempt to escape. The King and court temporarily moved to Oxford to avoid the plague, while Samuel Pepys remarked in his diary on 29 June, "By water to Whitehall, where the Court is full of waggons and people ready to go out of town. This end of town every day grows very bad with plague".


title: Whitehall

text: By the 18th century, traffic was struggling along the narrow streets south of Holbein Gate, which led to King Street Gate being demolished in 1723. Holbein Gate, in turn, was demolished in 1759. Meanwhile, Parliament Street was a side road alongside the palace, leading to the Palace of Westminster. After the Palace of Whitehall was destroyed, Parliament Street was widened to match Whitehall's width. The present appearance of the street dates from 1899 after a group of houses between Downing Street and Great George Street were destroyed.


title: Whitehall

text: In the 1970s, the IRA detonated some explosives in front of the Ministry of Agriculture building in Whitehall.


title: Whitehall

text: By the time the palace was destroyed, separation of crown and state had become important, with Parliament being necessary to control military requirements and pass laws. The government wanted to be some distance from the monarch, and the buildings around Whitehall, physically separated from St James's Palace by St James's Park, seemed to be a good place for ministers to work.


title: Whitehall

text: The Horse Guards building was designed by William Kent, and built during the 1750s on a former tiltyard site, replacing an earlier guard-house erected during the Civil War. The building includes an archway for coach traffic and two pedestrian arches that provide access between Whitehall and Horse Guards Parade. The central archway is marked with "SMF" and "StMW", and denotes the boundary between St Martin-in-the-Fields and St Margaret's church parish boundaries.


title: Whitehall

text: During the 19th century, as private leases ran out on residential buildings, ownership reverted to the Crown, which began to use them as public offices. The name "Whitehall" is now used as a metonym to refer to that part of the civil service which is involved in the government of the United Kingdom. The street's central portion is dominated by military buildings, including the Ministry of Defence, with the former headquarters of the British Army and Royal Navy, the Royal United Services Institute, the Horse Guards building and the Admiralty, on the opposite side. Government buildings on Whitehall, from north to south, include The Admiralty Buildings, the Department for International Development at No. 22, the Department of Energy and Climate Change at No. 55, the Old War Office, the Office of the Parliamentary Counsel at No. 36, the Horse Guards, the Ministry of Defence Main Building, Dover House (containing the Scotland Office), Gwydyr House (containing the Wales Office), the Cabinet Office at No. 70, the Foreign and Commonwealth Office and the Government Offices Great George Street (HM Treasury, HM Revenue and Customs and parts of the Cabinet Office).


title: Whitehall

text: Scotland Yard, the headquarters of London's Metropolitan Police Service, was originally located in Great Scotland Yard off the north-eastern end of Whitehall. The buildings had been lodgings for the Kings of Scotland, on part of the old Palace of Whitehall's grounds; by the 19th century, Little and Middle Scotland Yard had been merged into Whitehall Place, leaving only Great Scotland Yard. No. 4 Whitehall Place had become vacant by the 1820s, which allowed Sir Robert Peel to use it as the main headquarters when forming the police in 1829. It was formally named the Metropolitan Police Office, but became quickly known as Great Scotland Yard, and eventually Scotland Yard. The buildings were damaged in a series of bombings by Irish Nationalists in 1883, and an explosion from a Fenian terrorist attack on 30 May 1884 blew a hole in Scotland Yard's outer wall and destroyed the neighbouring Rising Sun pub. The headquarters was moved away from Whitehall in 1890.


title: Whitehall

text: Downing Street leads off the south-west end of Whitehall, just above Parliament Street. It was named after Sir George Downing, who built a row of houses along the street around 1680 leading west from Whitehall. Following a number of terrorist attacks, the road was closed to the public in 1990, when security gates were erected at both ends. On 7 February 1991, the Provisional IRA fired mortars from a van parked in Whitehall towards No. 10, one of which exploded in the gardens.


title: Whitehall

text: Additional security measures have been put in place along Whitehall to protect government buildings, following a £25 million streetscape project undertaken by Westminster City Council. The project has provided wider pavements and better lighting, along with installing hundreds of concrete and steel security barriers.


title: Whitehall

text: Richmond House, at No. 79, has held the Department of Health since 1987. The building is scheduled to be a temporary debating chamber from 2025, while the Houses of Parliament undergo a refurbishment and modernisation programme.


title: Whitehall

text: Statues and memorials have been built on and around Whitehall, commemorating military victories and leaders. The Cenotaph was designed by Sir Edwin Lutyens and erected at the southern end in 1919, commemorating victory in World War I and later used as a memorial for both World Wars. It is the main war memorial in Britain and an annual service is held here on Remembrance Sunday, led by the reigning monarch and leading politicians. In 2005, a national Monument to the Women of World War II was erected a short distance north of the Cenotaph in the middle of the Whitehall carriageway.


title: Whitehall

text: The Royal Tank Regiment Memorial is at the north east end of Whitehall, where Whitehall Court meets Whitehall Place. Erected in 2000, it commemorates the use of tanks in both World Wars and depicts five World War II tank crew members. The Gurkha Memorial is to the south of this, on Horse Guards Avenue to the east of Whitehall.


title: Whitehall

text: Whitehall is also home to six other monuments. From north to south, these are of Prince George, Duke of Cambridge (Commander-in-Chief of the British Army), Liberal Party, Liberal Unionist Party and Unionists leader Spencer Cavendish, 8th Duke of Devonshire, Douglas Haig, 1st Earl Haig (known as the Earl Haig Memorial), Field Marshal Montgomery (commander of the 8th Army, the 21st Army Group and Chief of the Imperial General Staff), William Slim, 1st Viscount Slim, Commander of the 14th Army and Governor-General of Australia, and Alan Brooke, 1st Viscount Alanbrooke, Chief of the Imperial General Staff.


title: Whitehall

text: The Whitehall Theatre opened in 1930 at the north west end of the street, on a site that had previously been Ye Old Ship Tavern in the 17th century. The revue "Whitehall Follies" opened in 1942, which drew controversy over its explicit content featuring the stripper and actress Phyllis Dixey. The theatre became known for its series of farces, reviving a tradition on Whitehall that had begun with court jesters at the palace during the 16th century; these included several plays featuring actor-manager Brian Rix throughout the 1950s and '60s, and 1981's satirical "Anyone for Denis", written by John Wells and "Private Eye" editor Richard Ingrams. The venue was Grade II listed in 1996 and renamed the Trafalgar Studios in 2004.


title: Whitehall

text: Because of its importance as a centre of British government, several political comedies are based in and around Whitehall. These include the BBC television series "Yes Minister" and "The Thick of It".


title: Whitehall

text: Whitehall is one of three purple squares on the British "Monopoly" board, along with Pall Mall and Northumberland Avenue. All three streets converge at Trafalgar Square.


title: Tacrolimus

text: Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T-cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs.


title: Tacrolimus

text: Tacrolimus inhibits calcineurin, which is involved in the production of interleukin-2, a molecule that promotes the development and proliferation of T cells, as part of the body's learned (or adaptive) immune response.


title: Tacrolimus

text: Chemically, it is a macrolide lactone that was first discovered in 1987, from the fermentation broth of a Japanese soil sample that contained the bacterium "Streptomyces tsukubensis".


title: Tacrolimus

text: It has similar immunosuppressive properties to ciclosporin, but is much more potent. Immunosuppression with tacrolimus was associated with a significantly lower rate of acute rejection compared with ciclosporin-based immunosuppression (30.7% vs 46.4%) in one study. Clinical outcome is better with tacrolimus than with ciclosporin during the first year of liver transplantation. Long-term outcome has not been improved to the same extent. Tacrolimus is normally prescribed as part of a post-transplant cocktail including steroids, mycophenolate, and IL-2 receptor inhibitors such as basiliximab. Dosages are titrated to target blood levels at specific times after medication administration.


title: Tacrolimus

text: As an ointment, tacrolimus is used in the treatment of eczema, in particular atopic dermatitis. It suppresses inflammation in a similar way to steroids, and is equally as effective as a mid-potency steroid. An important advantage of tacrolimus is that, unlike steroids, it does not cause skin thinning (atrophy), or other steroid related side effects.


title: Tacrolimus

text: It is applied on the active lesions until they heal off, but may also be used continuously in low doses (twice a week), and applied to the thinner skin over the face and eyelids. Clinical trials of up to one year have been conducted. Recently it has also been used to treat segmental vitiligo in children, especially in areas on the face.


title: Tacrolimus

text: Tacrolimus solution, as drops, is sometimes prescribed by veterinarians for keratoconjunctivitis, and other dry eye maladies, in the eyes of domestic cats, dogs, and horses. It has been studied for use in human eyes.


title: Tacrolimus

text: Side effects can be severe and include infection, cardiac damage, hypertension, blurred vision, liver and kidney problems (tacrolimus nephrotoxicity), hyperkalemia, hypomagnesemia, hyperglycemia, diabetes mellitus, itching, lung damage (sirolimus also causes lung damage), and various neuropsychiatric problems such as loss of appetite, insomnia, posterior reversible encephalopathy syndrome, confusion, weakness, depression, vivid nightmares, cramps, neuropathy, seizures, tremors, and catatonia.


title: Tacrolimus

text: In addition, it may potentially increase the severity of existing fungal or infectious conditions such as herpes zoster or polyoma viral infections.


title: Tacrolimus

text: In people receiving immunosuppressants to reduce transplant graft rejection, an increased risk of malignancy (cancer) is a recognised complication. The most common cancers are non-Hodgkin's lymphoma and skin cancers. The risk appears to be related to the intensity and duration of treatment.


title: Tacrolimus

text: The most common adverse events associated with the use of topical tacrolimus ointments, especially if used over a wide area, include a burning or itching sensation on the initial applications, with increased sensitivity to sunlight and heat on the affected areas. Less common are flu-like symptoms, headache, cough, and burning eyes.


title: Tacrolimus

text: Tacrolimus and a related drug for eczema (pimecrolimus) were suspected of carrying a cancer risk, though the matter is still a subject of controversy. The FDA issued a health warning in March 2005 for the drug, based on animal models and a small number of patients. Until further human studies yield more conclusive results, the FDA recommends that users be advised of the potential risks. However, current practice by UK dermatologists is not to consider this a significant real concern and they are increasingly recommending the use of these new drugs.


title: Tacrolimus

text: Also like cyclosporin, it has a wide range of interactions. Tacrolimus is primarily metabolised by the cytochrome P450 system of liver enzymes, and there are many substances that interact with this system and induce or inhibit the system's metabolic activity.


title: Tacrolimus

text: Interactions include that with grapefruit which increases tacrolimus plasma concentrations. As infections are a major cause of morbidity and mortality in the post-transplant patient, the most commonly reported interactions include interactions with anti-microbial drugs. Macrolide antibiotics including erythromycin and clarithromycin, as well as several of the newer classes of antifungals, especially of the azole class (fluconazole, voriconazole), increase tacrolimus levels by competing for cytochrome enzymes.


title: Tacrolimus

text: Tacrolimus is a macrolide calcineurin inhibitor. In T-cells, activation of the T-cell receptor normally increases intracellular calcium, which acts via calmodulin to activate calcineurin. Calcineurin then dephosphorylates the transcription factor nuclear factor of activated T-cells (NF-AT), which moves to the nucleus of the T-cell and increases the activity of genes coding for IL-2 and related cytokines. Tacrolimus prevents the dephosphorylation of NF-AT.


title: Tacrolimus

text: In detail, tacrolimus reduces peptidylprolyl isomerase activity by binding to the immunophilin FKBP12 (FK506 binding protein), creating a new complex. This FKBP12–FK506 complex interacts with and inhibits calcineurin, thus inhibiting both T-lymphocyte signal transduction and IL-2 transcription. Although this activity is similar to that of cyclosporin, the incidence of acute rejection is reduced by tacrolimus use over cyclosporin use. Although short-term immunosuppression concerning patient and graft survival is found to be similar between the two drugs, tacrolimus results in a more favorable lipid profile, and this may have important long-term implications given the prognostic influence of rejection on graft survival.


title: Tacrolimus

text: Oral tacrolimus is slowly absorbed in the gastrointestinal tract, with a total bioavailability of 20 to 25% (but with variations from 5 to 67%) and highest blood plasma concentrations (C) reached after one to three hours. Taking the drug together with a meal, especially one rich in fat, slows down resorption and reduces bioavailability. In the blood, tacrolimus is mainly bound to erythrocytes; only 5% are found in the plasma, of which more than 98.8% are bound to plasma proteins.


title: Tacrolimus

text: The substance is metabolized in the liver, mainly via CYP3A, and in the intestinal wall. All metabolites found in the circulation are inactive. Biological half-life varies widely and seems to be higher for healthy persons (43 hours on average) than for patients with liver transplants (12 hours) or kidney transplants (16 hours), due to differences in clearance. Tacrolimus is predominantly eliminated via the faeces in form of its metabolites.


title: Tacrolimus

text: The predominant enzyme responsible for metabolism of tacrolimus is CYP3A5. Genetic variations within "CYP3A5" that result in changes to the activity of the CYP3A5 protein can affect concentrations of tacrolimus within the body. In particular, individuals who are homozygous for the G allele at the single nucleotide polymorphism (SNP) rs776746 (also known as CYP3A5 *3/*3) have a non-functional CYP3A5 protein. The frequency of the G allele varies worldwide, from 4% in some African populations to 80–90% in Caucasian populations. Across a large number of studies, individuals homozygous for the G allele have been shown to have higher concentrations of tacrolimus and require lower doses of the drug, as compared to individuals who are not homozygous for the G allele. Achieving target concentrations of tacrolimus is important – if levels are too low, then there is a risk of transplant rejection, if levels are too high, there is a risk of drug toxicities. There is evidence to suggest that dosing patients based on rs776746 genotype can result in faster and more frequent achievement of target tacrolimus levels. However, there is a lack of consistent evidence as to whether dosing based on rs776746 genotype results in improved clinical outcomes (such as a decreased risk for transplant rejection or drug toxicities), likely because patients taking tacrolimus are subject to therapeutic drug monitoring.


title: Tacrolimus

text: Studies have shown that genetic polymorphisms of genes other than CYP3A5, such as NR1I2 (encoding PXR), also significantly influence the pharmacokinetics of tacrolimus.


title: Tacrolimus

text: Tacrolimus was discovered in 1987; it was among the first macrolide immunosuppressants discovered, preceded by the discovery of rapamycin (sirolimus) on Rapa Nui (Easter Island) in 1975. It is produced by a soil bacterium, "Streptomyces tsukubensis". The name tacrolimus is derived from "Tsukuba macrolide immunosuppressant".


title: Tacrolimus

text: Tacrolimus was first approved by the US Food and Drug Administration (FDA) in 1994, for use in liver transplantation; the indications were extended to include kidney transplants. Generic versions of tacrolimus were approved in the US in 2017.


title: Tacrolimus

text: Tacrolimus was approved for medical use in the European Union in 2002, for the treatment of moderate to severe atopic dermatitis. In 2007, the indications were expanded to include the prophylaxis of transplant rejection in adult kidney or liver allograft recipients and the treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adults. In 2009, the indications were expanded to include the prophylaxis of transplant rejection in adult and paediatric, kidney, liver or heart allograft recipients and the treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adults and children.


title: Tacrolimus

text: A branded version of the drug is owned by Astellas Pharma, and is sold under the brand name Prograf, given twice daily. A number of other manufacturers hold marketing authorisation for alternative brands of the twice-daily formulation.


title: Tacrolimus

text: Once-daily formulations with marketing authorisation include Advagraf (Astellas Pharma) and Envarsus (marketed as Envarsus XR in US by Veloxis Pharmaceuticals and marketed in Europe by Chiesi). These formulations are intended to reduce pharmacokinetic variation in blood levels and facilitate compliance with dosing.


title: Tacrolimus

text: The biosynthesis of tacrolimus is hybrid synthesis of both type 1 polyketide synthases (PKS 1) and nonribosomal peptide syntheses (NRPS). The research shows the hybrid synthesis consists of ten modules of type 1 polyketide synthase and one module of nonribosomal peptide synthase. The synthetic enzymes for tacrolimus are found in 19 gene clusters named fkb. The 19 genes are fkbQ, fkbN, fkbM, fkbD, fkbA, fkbP, fkbO, fkbB, fkbC, fkbL, fkbK, fkbJ, fkbI, fkbH, fkbG, allD, allR, allK and allA.


title: Tacrolimus

text: There are several possible ways of biosynthesis of tacrolimus. The fundamental units for biosynthesis are following: one molecule of 4,5-dihydroxycyclohex-1-enecarboxylic acid (DHCHC) as a starter unit, four molecules of malonyl-CoA, five molecules of methylmalonyl-CoA, one molecule of allylmalonyl-CoA as elongation units. However, two molecules of malonyl-CoA are able to be replaced by two molecules of methoxymalonyl CoA. Once two malonyl-CoA molecules are replaced, post-synthase tailoring steps are no longer required where two methoxymalonyl CoA molecules are substituted. The biosynthesis of methoxymalonyl CoA to Acyl Carrier protein is proceeded by five enzymes (fkbG, fkbH, fkbI, fkbJ, and fkbK). Allylmalonyl-CoA is also able to be replaced by propionylmalonyl-CoA.


title: Tacrolimus

text: The starter unit, DHCHC from the chorismic acid is formed by fkbO enzyme and loaded onto CoA-ligase domain (CoL). Then, it proceeds to NADPH dependent reduction(ER). Three enzymes, fkbA,B,C enforce processes from the loading module to the module 10, the last step of PKS 1. fkbB enzyme is responsible of allylmalonyl-CoA synthesis or possibly propionylmalonyl-CoA at C21, which it is an unusual step of general PKS 1. As mentioned, if two methoxymalonyl CoA molecules are substituted for two malonyl-CoA molecules, they will take place in module 7 and 8 (C13 and C15), and fkbA enzyme will enforce this process. After the last step (module 10) of PKS 1, one molecule of -pipecolic acid formed from -lysine and catalyzed through fkbL enzyme synthesizes with the molecule from the module 10. The process of -pipecolic acid synthesis is NRPS enforced by fkbP enzyme. After synthesizing the entire subunits, the molecule is cyclized. After the cyclization, the pre-tacrolimus molecule goes through the post-synthase tailoring steps such as oxidation and "S"-adenosyl methionine. Particularly fkbM enzyme is responsible of alcohol methylation targeting the alcohol of DHCHC starter unit (Carbon number 31 depicted in brown), and fkbD enzyme is responsible of C9 (depicted in green). After these tailoring steps, the tacrolimus molecule becomes biologically active.


title: Tacrolimus

text: Tacrolimus has been shown to reduce the risk of serious infections while also increasing remission of kidney function in lupus nephritis.


title: Tacrolimus

text: Tacrolimus has been used to suppress the inflammation associated with ulcerative colitis (UC), a form of inflammatory bowel disease. Although almost exclusively used in trial cases only, tacrolimus has shown to be significantly effective in the suppression of flares of UC. A 2022 updated Cochrane systematic review found that tacrolimus may be superior to placebo in achieving remission and improvement in UC.


title: Victor Frankenstein

text: Victor Frankenstein is a fictional character and the main protagonist and title character in Mary Shelley's 1818 novel, "Frankenstein; or, The Modern Prometheus".. He is an Italian-Swiss scientist (born in Naples, Italy) who, after studying chemical processes and the decay of living things, gains an insight into the creation of life and gives life to his own creature (often referred to as Frankenstein's monster, or often colloquially referred to as simply "Frankenstein"). Victor later regrets meddling with nature through his creation, as he inadvertently endangers his own life and the lives of his family and friends when the creature seeks revenge against him. He is first introduced in the novel when he is seeking to catch the monster near the North Pole and is saved from near death by Robert Walton and his crew.


title: Victor Frankenstein

text: Some aspects of the character are believed to have been inspired by 17th-century alchemist Johann Konrad Dippel. Certainly, the author and people in her environment were aware of the experiment on electricity and dead tissues by Luigi Galvani and his nephew Antonio Aldini and the work of Alessandro Volta at the University of Pavia.


title: Victor Frankenstein

text: Percy Shelley, Mary's husband, served as a significant influence for the character. Victor was a pen name of Percy Shelley's, as in the collection of poetry he wrote with his sister Elizabeth, "Original Poetry by Victor and Cazire". There is speculation that Percy was one of Mary Shelley's models for Victor Frankenstein; while a student at Eton College, he had "experimented with electricity and magnetism as well as with gunpowder and numerous chemical reactions", and his rooms at the University of Oxford were filled with scientific equipment. Percy Shelley was the first-born son of a wealthy, politically connected country squire, and a descendant of Sir Bysshe Shelley, 1st Baronet of Castle Goring, and Richard Fitzalan, 10th Earl of Arundel. As stated in the novel, Frankenstein's family is one of the most distinguished of the Genevese republic and his ancestors were counselors and syndics. Percy Shelley's sister and Frankenstein's adopted sister were both named Elizabeth. On 22 February 1815, Mary Shelley delivered a baby two months premature; the child died two weeks later. The question of Frankenstein's responsibility to the creature – in some ways like that of a parent to a child – is one of the main themes of the book.


title: Victor Frankenstein

text: One of the characters of 's novella "Le Miroir des événements actuels ou la Belle au plus offrant", published in 1790, is an inventor named "Wak-wik-vauk-an-son-frankésteïn", then abridged as "Frankésteïn", but there is no proof Shelley had read it.


title: Victor Frankenstein

text: Victor Frankenstein was born in Naples, Italy (according to the 1831 edition of Shelley's novel) with his Swiss family. He was the son of Alphonse Frankenstein and Caroline Beaufort, who died of scarlet fever when Victor was 17. He describes his ancestry thus: "I am by birth a Genevese; and my family is one of the most distinguished of that republic. My ancestors had been for many years counsellors and syndics; and my father had filled several public situations with honour and reputation." Frankenstein has two younger brothers—William, the youngest, and Ernest, the middle child. Frankenstein falls in love with Elizabeth Lavenza, who became his adoptive sister (his blood cousin in the 1818 edition) and, eventually, his fiancée.


title: Victor Frankenstein

text: As a boy, Frankenstein is interested in the works of alchemists such as Cornelius Agrippa, Paracelsus, and Albertus Magnus, and he longs to discover the fabled elixir of life. At the age of fifteen, he loses interest in both these pursuits and in science as a whole after he sees a tree destroyed by a lightning strike and a scientist explains the theory of electricity to him. It seems to him as if nothing can really be known about the world, and he instead devotes himself to studying mathematics, which he describes as "being built upon secure foundations." However, at the University of Ingolstadt in Bavaria, Frankenstein develops a fondness for chemistry, and within two years, his commitment and scientific ability allow him to make discoveries that earn him admiration at the university. He then becomes curious about the nature of life and his studies lead him to a miraculous discovery that enables him to create life in inanimate matter.


title: Victor Frankenstein

text: Assembling a humanoid creature through ambiguous means, Frankenstein successfully brings it to life, but he is horrified by the creature's ugliness. He flees from his creation, who disappears and, after several negative encounters with the locals, swears revenge on his creator. When William is found murdered, Frankenstein knows instantly that his creation is the killer, but says nothing. The Frankensteins' housekeeper, Justine, is blamed for the boy's death and executed; Frankenstein is wracked with guilt but does not come forward with the truth because he thinks no one will believe his story, and he is afraid of the reactions such a story would provoke.


title: Victor Frankenstein

text: The creature approaches Frankenstein and begs him to create a female companion for him. Frankenstein agrees, but ultimately destroys this creation, fearing the idea of a race of monsters. Enraged, the creature swears revenge; he kills Henry Clerval, Frankenstein's best friend, and promises Frankenstein, "I shall be with you on your wedding night." The creature keeps his promise by strangling Elizabeth on her matrimonial bed. Within a few days, Frankenstein's father dies of grief. With nothing else left to live for, Frankenstein dedicates his life to destroying the creature.


title: Victor Frankenstein

text: Frankenstein pursues the "fiend" or "Demon" (as he calls his creation) to the Arctic, intending to destroy it. Although he is rescued by a ship attempting an expedition to the North Pole, he dies after relating his tale to the ship's captain, Robert Walton. His creature, upon discovering the death of his creator, is overcome by sorrow and guilt and vows to commit suicide by burning himself alive in "the Northernmost extremity of the globe;” he then disappears, never to be seen or heard from again.


title: Victor Frankenstein

text: While many subsequent film adaptations (notably the 1931 movie "Frankenstein" and the Hammer Films series starring Peter Cushing) have portrayed Frankenstein as the prototypical "mad scientist", the novel portrayed him as a tragic figure.


title: Victor Frankenstein

text: In the book, Frankenstein has many characteristics of a great scientist. At a young age, he has the initiative to study natural philosophy and mathematics. As an adult, he attributes his accomplishments in chemistry to the effort he put into the discipline, rather than his intelligence. Frankenstein also has great curiosity about the world, and even recalls that some of his earliest memories were his realizations about the laws of nature. It is his curiosity about the cause of life that leads him to creating the monster.


title: Victor Frankenstein

text: Obsession plays a major role in the development of Frankenstein's character. First, as a child, he is obsessed with reading books on alchemy, astrology, and other pseudo-sciences. Later, as a young man, he often spends the entire night working in his laboratory. He then becomes enthralled with the study of life sciences - mainly dealing with death and the reanimation of corpses. Finally, after the monster is created, Frankenstein is consumed with guilt, despair, and regret, leading him to obsess over the nature of his creation.


title: Victor Frankenstein

text: Besides the original novel, the character also appears or is mentioned in other books from pastiches to parodies.


title: Languages of Morocco

text: There are a number of languages of Morocco. The two official languages are Standard Arabic and Standard Moroccan Berber. Moroccan Arabic (known as Darija) is the spoken native vernacular. The languages of prestige in Morocco are Arabic in its Classical and Modern Standard Forms and sometimes French, the latter of which serves as a second language for approximately 33% of Moroccans. According to a 2000–2002 survey done by Moha Ennaji, author of "Multilingualism, Cultural Identity, and Education in Morocco", "there is a general agreement that Standard Arabic, Moroccan Arabic, and Berber are the national languages." Ennaji also concluded "This survey confirms the idea that multilingualism in Morocco is a vivid sociolinguistic phenomenon, which is favored by many people."


title: Languages of Morocco

text: There are around 6 million Berber speakers in Morocco. French retains a major place in Morocco, as it is taught universally and serves as Morocco's primary language of commerce and economics, culture, sciences and medicine; it is also widely used in education and government. Morocco is a member of the Francophonie.


title: Languages of Morocco

text: Spanish is spoken by many Moroccans, particularly in the northern regions around Tetouan and Tangier, as well as in parts of the south, due to historic ties and business interactions with Spain.


title: Languages of Morocco

text: According to a 2012 study by the Government of Spain, 98% of Moroccans spoke Moroccan Arabic, 63% spoke French, 26% Berber, 14% spoke English, and 10% spoke Spanish.


title: Languages of Morocco

text: Historically, languages such as Phoenician, Punic, and Amazigh languages have been spoken in Morocco. Juba II, king of Mauretania, wrote in Greek and Latin. It is unclear how long African Romance was spoken, but its influence on Northwest African Arabic (particularly in the language of northwestern Morocco) indicates it must have had a significant presence in the early years after the Arab conquest.


title: Languages of Morocco

text: Arabic came with the Muslim conquest of the Maghreb; Abdellah Guennoun cites the Friday sermon delivered by Tariq Ibn Ziad just before the conquest of al-Andalus in 711 as the first instance of Moroccan literature in Arabic. However, the language spread much more slowly than the religion. At first, Arabic was used only in urban areas, especially in cities in the north, while the rural areas remained the domain of Amazigh languages.


title: Languages of Morocco

text: The first recorded work in Darija or Moroccan Arabic is Al-Kafif az-Zarhuni's epic "zajal" poem ""al-Mala'ba"," dating back to the reign of Marinid Sultan Abu al-Hasan Ali ibn Othman.


title: Languages of Morocco

text: After Morocco gained independence with the end of the French Protectorate in 1956, it started a process of Arabization. For this task, the Institute for Studies and Research on Arabization was established by decree in 1960. The policy of Arabization was not applied in earnest until 17 years after independence. An editorial in "Lamalif" in 1973 argued that, although French unified the elite and major sections of the economy, national unity could only be achieved based on Arabic—though "Lamalif" called for a new incarnation of the language, describing Standard Arabic as untenably prescriptive and Moroccan vernacular Arabic (Darija) as too poor to become in and of itself a language of culture and knowledge.


title: Languages of Morocco

text: In the year 2000, after years of neglecting and ignoring the other languages present in Morocco, the Charter for Educational Reform recognized them and the necessity for them.


title: Languages of Morocco

text: Until then the Berber languages were marginalized in the modern society and the number of monolingual speakers decreased. In recent years, the Berber culture has been gaining strength and some developments promise that these languages will not die (Berber is the generic name for the Berber languages. The term Berber is not used nor known by the speakers of these languages).


title: Languages of Morocco

text: Arabic, on the other hand, has been perceived as a prestigious language in Morocco for over a millennium. However, there are very distinctive varieties of Arabic used, not all equally prestigious, which are MSA (Modern Standard Arabic), the written form used in schools and ‘Dialectal Arabic’, the non-standardized spoken form. The difference between the two forms in terms of grammar, phonology and vocabulary is so great, it can be considered as diglossia. MSA is practically foreign to Moroccan schoolchildren, and this creates problems with reading and writing, consequently leading to a high level of illiteracy in Morocco.


title: Languages of Morocco

text: The French language is also dominant in Morocco, especially in education and administration, therefore was initially learned by an elite and later on was learned by a great number of Moroccans for use in domains such as finance, science, technology and media. That is despite the government decision to implement a language policy of ignoring French after gaining independence, for the sake of creating a monolingual country.


title: Languages of Morocco

text: From its independence until the year 2000, Morocco opted for Arabization as a policy, in an attempt of replacing French with Arabic. By the end of the 1980s, Arabic was the dominant language in education, although French was still in use in many important domains. The goals of Arabization were not met, in linguistic terms, therefore a change was needed.


title: Languages of Morocco

text: In 2000 the Charter of Educational Reform introduced a drastic change in language policy. From then on, Morocco has adopted a clear perpetual educational language policy with three main cores: improving and reinforcing the teaching of Arabic, using a variety of languages, such as English and French in teaching the fields of technology and science and acceptance of Berber. The state of Morocco still sees Arabic (MSA) as its national language, but acknowledges that not all Moroccans are Arabic speakers and that Arabization did not succeed in the area of science and technology. The aims of the Charter seem to have been met faster than expected, probably since the conditions of the Charter started to be implemented immediately. Nowadays the different minority languages are acknowledged in Morocco although Arabic still is the dominant one and is being promoted by the government.


title: Languages of Morocco

text: Framework Law 17:51 allowed scientific subjects to be taught in foreign languages—especially French—in public elementary schools.


title: Languages of Morocco

text: Arabic, along with Berber, is one of Morocco's two official languages, although it is the Moroccan dialect of Arabic, namely Darija, meaning "everyday/colloquial language"; that is spoken or understood, frequently as a second language, by the majority of the population (about 85% of the total population). Many native Berber speakers also speak the local Arabic variant as a second language. Arabic in its Classical and Standard forms is one of the two prestige languages in Morocco. Aleya Rouchdy, author of "Language Contact and Language Conflict in Arabic", said that Classical/Modern Arabic and French are constantly in conflict with one another, but that most Moroccans believe that the bilingualism of Classical Arabic and French is the most optimal choice to allow for Morocco's development.


title: Languages of Morocco

text: In 1995 the number of native Arabic speakers in Morocco was approximately 18.8 million (65% of the total population), and 21 million including the Moroccan diaspora.


title: Languages of Morocco

text: As a member of the Maghrebi Arabic grouping of dialects, Moroccan Arabic is similar to the dialects spoken in Mauritania, Algeria, Tunisia, and Libya (and also Maltese). The so called Darija dialect of Morocco is quite different from its Middle Eastern counterparts but in general understandable to each other, it’s estimated that Darija shares 70/75% of its vocabulary with Modern Standard Arabic. The country shows a marked difference in urban and rural dialects. This is due to the history of settlement. traditionally, Arabs established centers of power in only a few cities and ports in the region, with the effect that the other areas remained Berber-speaking. Then, in the 13th century, Bedouin tribes swept through many of the unsettled areas, spreading with them their distinct Arabic dialect in the non-urbanized areas and leaving speakers of Berber isolated in the mountainous regions.


title: Languages of Morocco

text: Moroccans learn Standard Arabic as a language. It is generally not spoken at home or on the streets. Standard Arabic is frequently used in administrative offices, mosques, and schools. According to Rouchdy, within Morocco Classical Arabic is still only used in literary and cultural aspects, formal traditional speeches, and discussions about religion.


title: Languages of Morocco

text: Moroccan Arabic, along with Berber, is one of two languages spoken in homes and on the street. The language is not used in writing. Abdelâli Bentahila, the author of the 1983 book "Language Attitudes among Arabic–French Bilinguals in Morocco", said that Moroccans who were bilingual in both French and Arabic preferred to speak Arabic while discussing religion; while discussing matters in a grocery store or restaurant; and while discussing matters with family members, beggars, and maids. Moha Ennaji, author of "Multilingualism, Cultural Identity, and Education in Morocco", said that Moroccan Arabic has connotations of informality, and that Moroccan Arabic tends to be used in casual conversations and spoken discourse. Ennaji added that Bilingual Moroccans tend to use Moroccan Arabic while in the house. Berbers generally learn Moroccan Arabic as a second language and use it as a "lingua franca", since not all versions of Berber are mutually intelligible with one another.


title: Languages of Morocco

text: The below table presents statistical figures of speakers, based on the 2014 population census. This table includes not only native speakers of Arabic, but also people who speak Arabic as a second or third language.


title: Languages of Morocco

text: Hassānīya, is spoken by about 0.8% of the population mainly in the Southern regions of Morocco. Communities of speakers exist elsewhere in Morocco too.


title: Languages of Morocco

text: The exact population of speakers of Berber languages is hard to ascertain, since most North African countries do not – traditionally – record language data in their censuses (An exception to this was the 2004 Morocco population census). The Ethnologue provides a useful academic starting point; however, its bibliographic references are inadequate, and it rates its own accuracy at only B-C for the area. Early colonial censuses may provide better documented figures for some countries; however, these are also very much out of date. The number for each Berber language is difficult to estimate.


title: Languages of Morocco

text: Berber serves as a vernacular language in many rural areas of Morocco. Berber, along with Moroccan Arabic, is one of two languages spoken in homes and on the street. The population does not use Berber in writing. Aleya Rouchdy, author of "Language Contact and Language Conflict in Arabic," said that Berber is mainly used in the contexts of family, friendship, and "street". In his 2000–2002 research, Ennaji found that 52% of the interviewees placed Berber as a language inferior to Arabic because it did not have a prestigious status and because its domain was restricted. Ennaji added that "[t]he dialectisation of Berber certainly reduces its power of communication and its spread."


title: Languages of Morocco

text: The language is spoken in the Rif area in the north of the country and is one of the three main Berber languages of Morocco.


title: Languages of Morocco

text: The Tashelhit language is considered to be the most widely spoken as it covers the whole of the Region Souss-Massa-Drâa, and is also spoken in the Marrakech-Tensift-El Haouz and Tadla-Azilal regions. Studies done in 1990 show around 3 million people, concentrated in the south of Morocco, speak the language.


title: Languages of Morocco

text: Central Morocco Tamazight is the second Berber language in Morocco. A 1998 study done by Ethnologue, shows that around 3 million people speak the language in Morocco. The language is most used in the regions Middle Atlas, High Atlas and east High Atlas Mountains.


title: Languages of Morocco

text: Other Berber languages are spoken in Morocco, as the Senhaja de Srair and the Ghomara dialects in the Rif mountains, the Figuig Shilha (not to be confused with Atlas Shilha) and Eastern Zenati in eastern Morocco, and Eastern Middle Atlas dialects in central Morocco.


title: Languages of Morocco

text: The below table presents statistical figures of speakers of Berber languages, based on the 2014 population census.


title: Languages of Morocco

text: "Few census figures are available; all countries (Algeria and Morocco included) do not count Berber languages. Population shifts in location and number, effects of urbanization and education in other languages, etc., make estimates difficult. In 1952 A. Basset (LLB.4) estimated the number of Berberophones at 5,500,000. Between 1968 and 1978 estimates ranged from eight to thirteen million (as reported by Galand, LELB 56, pp. 107, 123–25); Voegelin and Voegelin (1977, p. 297) call eight million a conservative estimate. In 1980, S. Chaker estimated that the Berberophone populations of Kabylie and the three Moroccan groups numbered more than one million each; and that in Algeria, 3,650,000, or one out of five Algerians, speak a Berber language (Chaker 1984, pp. 8-)


title: Languages of Morocco

text: In 1952, André Basset ("La langue berbère", Handbook of African Languages, Part I, Oxford) estimated that a "small majority" of Morocco's population spoke Berber. The 1960 census estimated that 34% of Moroccans spoke Berber, including bi-, tri-, and quadrilinguals. In 2000, Karl Prasse cited "more than half" in an interview conducted by Brahim Karada at Tawalt.com. According to the Ethnologue (by deduction from its Moroccan Arabic figures), the Berber-speaking population is estimated at 65% (1991 and 1995). However, the figures it gives for individual languages only add up to 7.5 million, or about 57%. Most of these are accounted for by three dialects:


title: Languages of Morocco

text: This nomenclature is common in linguistic publications, but is significantly complicated by local usage: thus Shilha is sub-divided into Shilha of the Dra valley, Tasusit (the language of the Souss) and several other (mountain) dialects. Moreover, linguistic boundaries are blurred, such that certain dialects cannot accurately be described as either Central Morocco Tamazight (spoken in the Central and eastern Atlas area) or Shilha. The differences among all Moroccan dialects are not too pronounced: public radio news are broadcast using the various dialects; each journalist speaks his or her own dialect with the result that understanding is not obstructed, though most southern Berbers find that understanding Riff requires some getting used to.


title: Languages of Morocco

text: Within Morocco, French, one of the country's two prestige languages, is often used for business, diplomacy, and government; and serves as a lingua franca. Aleya Rouchdy, author of "Language Contact and Language Conflict in Arabic", said that "For all practical purposes, French is used as a second language."


title: Languages of Morocco

text: Different figures of French speakers in Morocco are given. According to the OIF, 33% of Moroccans speak French, among them 13.5% fully francophone and thus bilingual with one of the other Moroccan languages, and 19.5% partially francophone. According to the 2004 census, nearly 69% of literate people can read and write French.


title: Languages of Morocco

text: It is also the mother language of some Moroccans, regrouped mainly in the western side of the country (Casablanca and Rabat mainly, but also many other cities).


title: Languages of Morocco

text: In a survey from 2005 by the CIDOB (Barcelona Centre for International Affairs), 21.9% of respondents from Morocco claimed to speak Spanish, with higher percentages in the northern regions. The use of Spanish in northern Morocco and Western Sahara derives largely from the fact that Spain had previously occupied those areas and incorporated Spanish Sahara as a province. In these regions Spanish television is often watched and there are interactions in Spanish on a daily basis.


title: Languages of Morocco

text: After Morocco declared independence in 1956, French and Arabic became the main languages of administration and education, causing the role of Spanish to decline.


title: Languages of Morocco

text: Today, Spanish is still offered as one of the foreign languages in the educational system but has fallen well behind French and English. According to the Cervantes Institute, there were 11,409 students learning Spanish in Morocco in 2017, a large decline from about 50,000 in 2005. Demand for Spanish and overall competency in the language has fallen overall since the start of the 21st century.


title: ATX

text: ATX (Advanced Technology eXtended) is a motherboard and power supply configuration specification developed by Intel in 1995 to improve on previous de facto standards like the AT design. It was the first major change in desktop computer enclosure, motherboard and power supply design in many years, improving standardization and interchangeability of parts. The specification defines the dimensions; the mounting points; the I/O panel; and the power and connector interfaces among a computer case, a motherboard, and a power supply.


title: ATX

text: ATX is the most common motherboard design. Other standards for smaller boards (including microATX, FlexATX, nano-ITX, and mini-ITX) usually keep the basic rear layout but reduce the size of the board and the number of expansion slots. Dimensions of a full-size ATX board are , which allows many ATX chassis to accept microATX boards. The ATX specifications were released by Intel in 1995 and have been revised numerous times since. The most recent ATX motherboard specification is version 2.2. The most recent ATX12V power supply unit specification is 2.53, released in June 2020. EATX (Extended ATX) is a bigger version of the ATX motherboard with dimensions. While some dual CPU socket motherboards have been implemented in ATX, the extra size of EATX makes it the typical form factor for dual socket systems, and with sockets that support four or eight memory channels, for single socket systems with a large number of memory slots.


title: ATX

text: In 2004, Intel announced the BTX (Balanced Technology eXtended) standard, intended as a replacement for ATX. While some manufacturers adopted the new standard, Intel discontinued any future development of BTX in 2006. , the ATX design still remains the de facto standard for personal computers.


title: ATX

text: On the back of the computer case, some major changes were made to the AT standard. Originally AT style cases had only a keyboard connector and expansion slots for add-on card backplates. Any other onboard interfaces (such as serial and parallel ports) had to be connected via flying leads to connectors which were mounted either on spaces provided by the case or brackets placed in unused expansion slot positions.


title: ATX

text: ATX allowed each motherboard manufacturer to put these ports in a rectangular area on the back of the system with an arrangement they could define themselves, though a number of general patterns depending on what ports the motherboard offers have been followed by most manufacturers. Cases are usually fitted with a snap-out panel, also known as an I/O plate or I/O shield, in one of the common arrangements. If necessary, I/O plates can be replaced to suit a motherboard that is being fitted; the I/O plates are usually included with motherboards not designed for a particular computer. The computer will operate correctly without a plate fitted, although there will be open gaps in the case which may compromise the EMI/RFI screening and allow ingress of dirt and random foreign bodies. Panels were made that allowed fitting an AT motherboard in an ATX case. Some ATX motherboards come with an integrated I/O plate.


title: ATX

text: ATX also made the PS/2-style mini-DIN keyboard and mouse connectors ubiquitous. AT systems used a 5-pin DIN connector for the keyboard and were generally used with serial port mice (although PS/2 mouse ports were also found on some systems). Many modern motherboards are phasing out the PS/2-style keyboard and mouse connectors in favor of the more modern Universal Serial Bus. Other legacy connectors that are slowly being phased out of modern ATX motherboards include 25-pin parallel ports and 9-pin RS-232 serial ports. In their place are onboard peripheral ports such as Ethernet, FireWire, eSATA, audio ports (both analog and S/PDIF), video (analog D-sub, DVI, HDMI, or DisplayPort), extra USB ports, and Wi-Fi.


title: ATX

text: A notable issue with the ATX specification was that it was last revised when power supplies were normally placed at the top, rather than the bottom, of computer cases. This has led to some problematic standard locations for ports, in particular the 4/8 pin CPU power, which is normally located along the top edge of the board to make it convenient for top mounted power supplies. This makes it very difficult for cables from bottom mounted power supplies to reach, and commonly requires a special cutout in the back plane for the cable to come in from behind and bend around the board, making insertion and wire management very difficult. Many power supply cables barely reach or fail to reach, or are too stiff to make the bend, and extensions are commonly required due to this placement.


title: ATX

text: Several ATX-derived designs have been specified that use the same power supply, mountings and basic back panel arrangement, but set different standards for the size of the board and number of expansion slots. Standard ATX provides seven slots at spacing; the popular microATX size removes and three slots, leaving four. Here width refers to the distance along the external connector edge, while depth is from front to rear. Note each larger size inherits all previous (smaller) colors area.


title: ATX

text: AOpen has conflated the term Mini ATX with a more recent design. Since references to Mini ATX have been removed from ATX specifications since the adoption of microATX, the AOpen definition is the more contemporary term and the one listed above is apparently only of historical significance. This sounds contradictory to the now common Mini-ITX standard (), which is a potential source of confusion. A number of manufacturers have added one to three additional expansion slots (at the standard 0.8 inch spacing) to the standard 12-inch ATX motherboard width.


title: ATX

text: Form factors considered obsolete in 1999 included Baby-AT, full size AT, and the semi-proprietary LPX for low-profile cases. Proprietary motherboard designs such as those by Compaq, Packard-Bell, Hewlett Packard and others existed, and were not interchangeable with multi-manufacturer boards and cases. Portable and notebook computers and some 19-inch rackmount servers have custom motherboards unique to their particular products.


title: ATX

text: Although true E-ATX is most motherboard manufacturers also refer to motherboards with measurements , , and as E-ATX. While E-ATX and SSI EEB (Server System Infrastructure (SSI) Forum's Enterprise Electronics Bay (EEB)) share the same dimensions, the screw holes of the two standards do not all align; rendering them incompatible.


title: ATX

text: In 2008, Foxconn unveiled a Foxconn F1 motherboard prototype, which has the same width as a standard ATX motherboard, but an extended 14.4" length to accommodate 10 slots. The firm called the new design of this motherboard "Ultra ATX" in its CES 2008 showing. Also unveiled during the January 2008 CES was the Lian Li Armorsuit PC-P80 case with 10 slots designed for the motherboard.


title: ATX

text: In 2010, EVGA Corporation released a new motherboard, the "Super Record 2", or SR-2, whose size surpasses that of the "EVGA X58 Classified 4-Way SLI". The new board is designed to accommodate two Dual QPI LGA1366 socket CPUs (e.g. Intel Xeon), similar to that of the Intel Skulltrail motherboard that could accommodate two Intel Core 2 Quad processors and has a total of seven PCI-E slots and 12 DDR3 RAM slots. The new design is dubbed "HPTX" and is .


title: ATX

text: The ATX specification requires the power supply to produce three main outputs, +3.3 V, +5 V and +12 V. Low-power −12 V and +5 V (standby) supplies are also required. The −12 V supply is primarily used to provide the negative supply voltage for RS-232 ports and is also used by one pin on conventional PCI slots primarily to provide a reference voltage for some models of sound cards. The 5 V supply is used to produce trickle power to provide the soft-power feature of ATX when a PC is turned off, as well as powering the real-time clock to conserve the charge of the CMOS battery. A −5 V output was originally required because it was supplied on the ISA bus; it was removed in later versions of the ATX standard, as it became obsolete with the removal of the ISA bus expansion slots (the ISA bus itself is still found in any computer which is compatible with the old IBM PC specification; e.g., not found in the PlayStation 4).


title: ATX

text: Originally, the motherboard was powered by one 20-pin connector. An ATX power supply provides a number of peripheral power connectors and (in modern systems) two connectors for the motherboard: an 8-pin (or 4+4-pin) auxiliary connector providing additional power to the CPU and a main 24-pin power supply connector, an extension of the original 20-pin version. 20-pin MOLEX 39-29-9202 at the motherboard. 20-pin MOLEX 39-01-2200 at the cable. The connector pin pitch is 4.2 mm (one sixth of an inch).


title: ATX

text: Generally, supply voltages must be within ±5% of their nominal values at all times. The little-used negative supply voltages, however, have a ±10% tolerance. There is a specification for ripple in a 10 Hz–20 MHz bandwidth:


title: ATX

text: The 20–24-pin Molex Mini-Fit Jr. has a power rating of 600 volts, 8 amperes maximum per pin (while using 18 AWG wire). As large server motherboards and 3D graphics cards have required progressively more and more power to operate, it has been necessary to revise and extend the standard beyond the original 20-pin connector, to allow more current using multiple additional pins in parallel. The low circuit voltage is the restriction on power flow through each connector pin; at the maximum rated voltage, a single Mini-Fit Jr pin would be capable of 4800 watts.


title: ATX

text: ATX power supplies generally have the dimensions of , with the width and height being the same as the preceding LPX (Low Profile eXtension) form factor (which are often incorrectly referred to as "AT" power supplies due to their ubiquitous use in later AT and Baby AT systems, even though the actual AT and Baby AT power supply form factors were physically larger) and share a common mounting layout of four screws arranged on the back side of the unit. That last dimension, the 140 mm depth, is frequently varied, with depths of 160, 180, 200 and 230 mm used to accommodate higher power, larger fan and/or modular connectors.


title: ATX

text: Original AT cases (flat case style) have an integrated power switch that protruded from the power supply and


title: ATX

text: sits flush with a hole in the AT chassis. It utilizes a paddle-style DPST switch and is similar to the PC and PC-XT style power supplies.


title: ATX

text: Later AT (so-called "Baby AT") and LPX style computer cases have a power button that is directly connected to the system computer power supply (PSU). The general configuration is a double-pole latching mains voltage switch with the four pins connected to wires from a four-core cable. The wires are either soldered to the power button (making it difficult to replace the power supply if it failed) or blade receptacles were used.


title: ATX

text: An ATX power supply is typically controlled by an electronic switch connected to the power button on the computer case and allows the computer to be turned off by the operating system. In addition, many ATX power supplies have a manual switch on the back that also ensures no power is being sent to the components. When the switch on the power supply is turned off, the computer cannot be turned on with the front power button.


title: ATX

text: The power supply's connection to the motherboard was changed from the older AT and LPX standards; AT and LPX had two similar connectors that could be accidentally interchanged by forcing the different keyed connectors into place, usually causing short-circuits and irreversible damage to the motherboard (the rule of thumb for safe operation was to connect the side-by-side connectors with the black wires together). ATX uses one large, keyed connector which can not be connected incorrectly. The new connector also provides a 3.3 volt source, removing the need for motherboards to derive this voltage from the 5 V rail. Some motherboards, particularly those manufactured after the introduction of ATX but while LPX equipment was still in use, support both LPX and ATX PSUs.


title: ATX

text: If using an ATX PSU for purposes other than powering an ATX motherboard, power can be fully turned on (it is always partly on to operate "wake-up" devices) by shorting the "power-on" pin on the ATX connector (pin 16, green wire) to a black wire (ground), which is what the power button on an ATX system does. A minimum load on one or more voltages may be required (varies by model and vendor); the standard does not specify operation without a minimum load and a conforming PSU may shut down, output incorrect voltages, or otherwise malfunction, but will not be hazardous or damaged. An ATX power supply is not a replacement for a current-limited bench laboratory DC power supply; instead it is better described as a bulk DC power supply.


title: ATX

text: The original ATX specification called for a power supply to be located near to the CPU with the power supply fan drawing in cooling air from outside the chassis and directing it onto the processor. It was thought that in this configuration, cooling of the processor would be achievable without the need of an active heatsink. This recommendation was removed from later specifications; modern ATX power supplies usually exhaust air from the case.


title: ATX

text: The power distribution specification defined that most of the PSU's power should be provided on 5 V and 3.3 V rails, because most of the electronic components (CPU, RAM, chipset, PCI, AGP and ISA cards) used 5 V or 3.3 V for power supply. The 12 V rail was only used by computer fans and motors of peripheral devices (HDD, FDD, CD-ROM, etc.)


title: ATX

text: While designing the Pentium 4 platform in 1999/2000, the standard 20-pin ATX power connector was found insufficient to meet increasing power-line requirements; the standard was significantly revised into ATX12V 1.0 (ATX12V 1.x is sometimes inaccurately called ATX-P4). ATX12V 1.x was also adopted by AMD Athlon XP and Athlon 64 systems. However, some early model Athlon XP and MP boards (including some server boards) and later model lower-end motherboards do not have the 4-pin connector as described below.


title: ATX

text: Numbering of the ATX revisions may be a little confusing: ATX refers to the design, and goes up to version 2.2 in 2004 (with the 24 pins of ATX12V 2.0), while ATX12V describes only the PSU.


title: ATX

text: For instance, ATX 2.03 is quite commonly seen on PSUs from 2000 and 2001 and often includes the P4 12V connector, even if the norm itself did not define it yet.


title: ATX

text: Formally called the "+12 V Power Connector", this is commonly referred to as the P4 connector because this was first needed to support the Pentium 4 processor.


title: ATX

text: Before the Pentium 4, processors were generally powered from the 5 V rail. Later processors operate at much lower voltages, typically around 1 V and some draw over 100 A. It is infeasible to provide power at such low voltages and high currents from a standard system power supply, so the Pentium 4 established the practice of generating it with a DC-to-DC converter on the motherboard next to the processor, powered by the 4-pin 12 V connector.


title: ATX

text: This is a minor revision from August 2000. The power on the 3.3 V rail was slightly increased and other smaller changes were made.


title: ATX

text: A relatively minor revision from January 2002. The only significant change was that the −5 V rail was no longer required (it became optional). This voltage was required by the ISA bus, which is no longer present on almost all modern computers.


title: ATX

text: Introduced in April 2003 (a month after 2.0). This standard introduced some changes, mostly minor. Some of them are:


title: ATX

text: ATX12V 2.x brought a significant design change regarding power distribution. By analyzing the power demands of then-current PCs, it was determined that it would be much cheaper and more practical to power most PC components from 12 V rails, instead of from 3.3 V and 5 V rails.


title: ATX

text: In particular, PCI Express expansion cards take much of their power from the 12 V rail (up to 5.5 A), while the older AGP graphics cards took only up to 1 A on 12 V and up to 6 A on 3.3 V. The CPU is also driven by a 12 V rail, while it was done by a 5 V rail on older PCs (before the Pentium 4).


title: ATX

text: The power demands of PCI Express were incorporated in ATX12V 2.0 (introduced in February 2003), which defined quite different power distribution from ATX12V 1.x:


title: ATX

text: This is a minor revision from June 2004. An errant reference for the −5 V rail was removed. Other minor changes were introduced.


title: ATX

text: This is a minor revision from March 2005. The power was slightly increased on all rails. Efficiency requirements changed: minimum 65% at light load, 72% at typical load, and 70% at full load. Introduced recommended minimum values of 75% at light load, 80% at typical load, and 77% at full load.


title: ATX

text: Also released in March 2005 it includes corrections and specifies High Current Series wire terminals for 24-pin ATX motherboard and 4-pin +12 V power connectors.


title: ATX

text: Effective March 2007. Recommended efficiency was increased to 80% (with at least 70% required) and the 12 V minimum load requirement was lowered. Higher efficiency generally results in less power consumption (and less waste heat) and the 80% recommendation brings supplies in line with new Energy Star 4.0 mandates. The reduced load requirement allows compatibility with processors that draw very little power during startup. The absolute over-current limit of 240 VA per rail was removed, allowing 12 V lines to provide more than 20 A per rail.


title: ATX

text: This revision became effective in February 2008. It added a maximum allowed ripple/noise specification of 400 millivolts to the PWR_ON and PWR_OK signals, requires that the DC power must hold for more than 1 millisecond after the PWR_OK signal drops, clarified country-specific input line harmonic content and electromagnetic compatibility requirements, added a section about Climate Savers, updated recommended power supply configuration charts, and updated the cross-regulation graphs.


title: ATX

text: The ATX12V 2.4 specifications were published in April 2013. It is specified in Revision 1.31 of the 'Design Guide for Desktop Platform Form Factors', which names this as ATX12V version 2.4.


title: ATX

text: The specifications for ATXV12 2.51 were released in October 2017 and introduced support for "Alternative Sleep Mode (ASM)" which supersedes the traditional S3 power state. Windows 10 implements this functionality as "Modern Standby".


title: ATX

text: The specifications for ATXV12 2.52 were released in May 2018 introduces minor changes to the standard, most notably it requires power supply manufacturers to ensure power supplies with "Alternative Sleep Mode (ASM)" support are able to withstand power cycles every 180 seconds (480 times per day or 175,200 per year). Power supply fans are also recommended to turn on with at least a two second delay for an improved user experience.


title: ATX

text: The specifications for ATXV12 2.53 were released in May 2020 and constitute another minor update to the ATX standard. ATXV12 2.53 makes further recommendations on efficiency and references the Energy Star "Computers Specification Version 8.0" which was finalized in April 2020.


title: ATX

text: The specifications for ATX 3.0 were released in February 2022. It includes the new 16-pin 12VHPWR connector that can deliver up to 600 W to graphics cards. These incorporate data lines for components to negotiate power capabilities with the PSU so they do not draw more power than the PSU is capable of delivering. The specification also has more strict requirements for handling spikes.


title: ATX

text: Standing for ATX 12-volt-only, this is a new specification published by Intel in 2019, aimed at pre-built systems in the first run, and stricter power efficiency requirements by the California Energy Commission going into effect in 2021. Several OEMs were already using a similar design with proprietary connectors and this effectively standardizes those.


title: ATX

text: Under this standard, power supplies provide only a 12 V output. ATX12VO introduces a new 10-pin connector to supply the motherboard, replacing the 24-pin ATX12V connector. This greatly simplifies power supplies, but moves DC-to-DC conversion and some connectors to the motherboard instead. Notably, SATA power connectors, which include 3.3 V and 5 V pins, need to move to the motherboard instead of being connected directly to the power supply.


title: ATX

text: SFX is merely a design for a small form factor (SFF) power supply casing (such as those using microATX, FlexATX, nano-ITX, mini-ITX, and NLX), with the power specifications almost identical to ATX. Thus, an SFX power supply is mostly pin-compatible with the ATX power supply as the main difference is its reduced dimensions; the only electrical difference is that the SFX specifications do not require the −5 V rail. Since −5 V is required only by some ISA-bus expansion cards, this is not an issue with modern hardware and decreases productions costs. As a result, ATX pin 20, which carried −5 V, is absent in current power supplies; it was optional in ATX and ATX12V version 1.2 and deleted as of ATX version 1.3.


title: ATX

text: SFX has dimensions of 125 × 63.5 × 100 mm (width × height × depth), with a 60 mm fan, compared with the standard ATX dimensions of 150 × 86 × 140 mm. Optional 80 or 40 mm fan replacement increases or decreases the height of an SFX unit.


title: ATX

text: Some manufacturers and retailers incorrectly market SFX power supplies as μATX or MicroATX power supplies.


title: ATX

text: Thin Form Factor is another small power supply design with standard ATX specification connectors. Its dimensions are generally (W × H × D): 85 × 64 × 175 mm (3.34 × 2.52 × 6.89 in).


title: ATX

text: WTX power supplies provide a WTX style motherboard connector which is incompatible with the standard ATX motherboard connector.


title: ATX

text: This is an ATX12V power supply derivative made by AMD to power its Athlon MP (dual processor) platform. It was used only on high-end Athlon MP motherboards. It has a special 8-pin supplemental connector for motherboard, so an AMD GES PSU is required for such motherboards (those motherboards will not work with ATX(12 V) PSUs).


title: ATX

text: a. ATX12V-GES 24-pin P1 motherboard connector. The pinout on the motherboard connector is as follows when viewing the motherboard from above:


title: ATX

text: b. ATX12V-GES 8-pin P2 motherboard connector. This pinout on the motherboard connector is as follows when viewing the motherboard from above:


title: ATX

text: EPS12V is defined in Server System Infrastructure (SSI) and used primarily by SMP/multi-core systems such as Core 2, Core i7, Opteron and Xeon. It has a 24-pin ATX motherboard connector (same as ATX12V v2.x), an 8-pin secondary connector and an optional 4-pin tertiary connector. Rather than include the extra cable, many power supply makers implement the 8-pin connector as two combinable 4-pin connectors to ensure backwards compatibility with ATX12V motherboards.


title: ATX

text: High-performance video card power demands dramatically increased during the 2000s and some high-end graphics cards have power demands that exceed AGP or PCIe slot capabilities. For these cards, supplementary power was delivered through a standard 4-pin peripheral or floppy power connector. Midrange and high-end PCIe graphics cards manufactured after 2004 typically use a standard 6 or 8-pin PCIe power connector directly from the PSU.


title: ATX

text: Although the ATX power supply specifications are mostly vertically compatible in both ways (both electrically and physically), there are potential issues with mixing old motherboards/systems with new PSUs and vice versa. The main issues to consider are the following:


title: ATX

text: Some proprietary brand-name systems require a matching proprietary power supply, but some of them may also support standard and interchangeable power supplies.


title: ATX

text: Efficiency in power supplies means the extent to which power is not wasted in converting electricity from a household supply to regulated DC. Computer power supplies vary from around 70% to over 90% efficiency.


title: ATX

text: Various initiatives exist to improve the efficiency of computer power supplies. Climate Savers Computing Initiative promotes energy saving and reduction of greenhouse gas emissions by encouraging development and use of more efficient power supplies. 80 PLUS certifies a variety of efficiency levels for power supplies and encourages their use via financial incentives. Efficient power supplies also save money by wasting less power; as a result they use less electricity to power the same computer, and they emit less waste heat which results in significant energy savings on central air conditioning in the summer. The gains of using an efficient power supply are more substantial in computers that use a lot of power.


title: ATX

text: Although a power supply with a larger than needed power rating will have an extra margin of safety against overloading, such a unit is often less efficient and wastes more electricity at lower loads than a more appropriately sized unit. For example, a 900-watt power supply with the 80 Plus Silver efficiency rating (which means that such a power supply is designed to be at least 85 percent efficient for loads above 180 W) may only be 73% efficient when the load is lower than 100 W, which is a typical idle power for a desktop computer. Thus, for a 100 W load, losses for this supply would be 27 W; if the same power supply was put under a 450 W load, for which the supply's efficiency peaks at 89%, the loss would be only 56 W despite supplying 4.5 times the useful power. For a comparison, a 500-watt power supply carrying the 80 Plus Bronze efficiency rating (which means that such a power supply is designed to be at least 82-percent efficient for loads above 100 W) may provide an 84 percent efficiency for a 100 W load, wasting only 19 W.


title: Electric vehicle battery

text: An electric vehicle battery (EVB, also known as a traction battery) is a rechargeable battery used to power the electric motors of a battery electric vehicle (BEV) or hybrid electric vehicle (HEV). Typically lithium-ion batteries, they are specifically designed for high electric charge (or energy) capacity.


title: Electric vehicle battery

text: Electric vehicle batteries differ from starting, lighting, and ignition (SLI) batteries as they are designed to give power over sustained periods of time and are deep-cycle batteries. Batteries for electric vehicles are characterized by their relatively high power-to-weight ratio, specific energy and energy density; smaller, lighter batteries are desirable because they reduce the weight of the vehicle and therefore improve its performance. Compared to liquid fuels, most current battery technologies have much lower specific energy, and this often impacts the maximum all-electric range of the vehicles.


title: Electric vehicle battery

text: The most common battery type in modern electric vehicles are lithium-ion and lithium polymer, because of their high energy density compared to their weight. Other types of rechargeable batteries used in electric vehicles include lead–acid ("flooded", deep-cycle, and valve regulated lead acid), nickel-cadmium, nickel–metal hydride, and, less commonly, zinc–air, and sodium nickel chloride ("zebra") batteries. The amount of electricity (i.e. electric charge) stored in batteries is measured in ampere hours or in coulombs, with the total energy often measured in kilowatt-hours (kWh).


title: Electric vehicle battery

text: Since the late 1990s, advances in lithium-ion battery technology have been driven by demands from portable electronics, laptop computers, mobile phones, and power tools. The BEV and HEV marketplace has reaped the benefits of these advances both in performance and energy density. Unlike earlier battery chemistries, notably nickel-cadmium, lithium-ion batteries can be discharged and recharged daily and at any state of charge.


title: Electric vehicle battery

text: The battery pack makes up a significant cost of a BEV or a HEV. , the cost of electric vehicle batteries has fallen 87% since 2010 on a per kilowatt-hour basis. As of 2018, vehicles with over of all-electric range, such as the Tesla Model S, have been commercialized and are now available in numerous vehicle segments.


title: Electric vehicle battery

text: In terms of operating costs, the price of electricity to run a BEV is a small fraction of the cost of fuel for equivalent internal combustion engines, reflecting higher energy efficiency.


title: Electric vehicle battery

text: Flooded lead-acid batteries are the oldest, cheapest, and, in the past, most common vehicle batteries available. There are two main types of lead-acid batteries: automobile engine starter batteries, and deep cycle batteries. Automobile engine starter batteries are designed to use a small percentage of their capacity to provide high charge rates to start the engine, while deep cycle batteries are used to provide continuous electricity to run electric vehicles like forklifts or golf carts. Deep cycle batteries are also used as the auxiliary batteries in recreational vehicles, but they require different, multi-stage charging. No lead acid battery should be discharged below 50% of its capacity, as it shortens the battery's life. Flooded batteries require inspection of electrolyte levels and occasional replacement of water, which gases away during the normal charging cycle.


title: Electric vehicle battery

text: Previously, most electric vehicles used lead-acid batteries due to their mature technology, high availability, and low cost, with the notable exception of some early BEVs, such as the Detroit Electric which used a nickel–iron battery. Deep-cycle lead batteries are expensive and have a shorter life than the vehicle itself, typically needing replacement every 3 years.


title: Electric vehicle battery

text: Lead-acid batteries in EV applications end up being a significant (25–50%) portion of the final vehicle mass. Like all batteries, they have significantly lower specific energy than petroleum fuels—in this case, 30–50 W⋅h/kg. While the difference isn't as extreme as it first appears due to the lighter drive-train in an EV, even the best batteries tend to lead to higher masses when applied to vehicles with a normal range. The efficiency (70–75%) and storage capacity of the current generation of common deep cycle lead acid batteries decreases with lower temperatures, and diverting power to run a heating coil reduces efficiency and range by up to 40%.


title: Electric vehicle battery

text: Charging and operation of batteries typically results in the emission of hydrogen, oxygen and sulfur, which are naturally occurring and normally harmless if properly vented. Early Citicar owners discovered that, if not vented properly, unpleasant sulfur smells would leak into the cabin immediately after charging.


title: Electric vehicle battery

text: Nickel-metal hydride batteries are now considered a relatively mature technology. While less efficient (60–70%) in charging and discharging than even lead-acid, they have a specific energy of 30–80 W⋅h/kg, far higher than lead-acid. When used properly, nickel-metal hydride batteries can have exceptionally long lives, as has been demonstrated in their use in hybrid cars and in the surviving first-generation NiMH Toyota RAV4 EVs that still operate well after and over a decade of service. Downsides include the poor efficiency, high self-discharge, very finicky charge cycles, and poor performance in cold weather.


title: Electric vehicle battery

text: GM Ovonic produced the NiMH battery used in the second generation EV-1, and Cobasys makes a nearly identical battery (ten 1.2 V 85 A⋅h NiMH cells in series in contrast with eleven cells for Ovonic battery). This worked very well in the EV-1. Patent encumbrance has limited the use of these batteries in recent years.


title: Electric vehicle battery

text: The sodium nickel chloride or "Zebra" battery uses a molten sodium chloroaluminate (NaAlCl) salt as the electrolyte. A relatively mature technology, the Zebra battery has a specific energy of 120 W⋅h/kg. Since the battery must be heated for use, cold weather does not strongly affect its operation except for increasing heating costs. They have been used in several EVs such as the Modec commercial vehicle. Zebra batteries can last for a few thousand charge cycles and are nontoxic. The downsides to the Zebra battery include poor specific power (<300 W/kg) and the requirement of having to heat the electrolyte to about , which wastes some energy, presents difficulties in long-term storage of charge, and is potentially a hazard.


title: Electric vehicle battery

text: lithium-ion (and the mechanistically similar lithium polymer) batteries, were initially developed and commercialized for use in laptops and consumer electronics. With their high energy density and long cycle life they have become the leading battery type for use in EVs. The first commercialized lithium-ion chemistry was a lithium cobalt oxide cathode and a graphite anode first demonstrated by N. Godshall in 1979, and by John Goodenough, and Akira Yoshino shortly thereafter. The downside of traditional lithium-ion batteries include sensitivity to temperature, low temperature power performance, and performance degradation with age. Due to the volatility of organic electrolytes, the presence of highly oxidized metal oxides, and the thermal instability of the anode SEI layer, traditional lithium-ion batteries pose a fire safety risk if punctured or charged improperly. These early cells did not accept or supply charge when extremely cold, and so heaters can be necessary in some climates to warm them. The maturity of this technology is moderate. The Tesla Roadster (2008) and other cars produced by the company used a modified form of traditional lithium-ion "laptop battery" cells.


title: Electric vehicle battery

text: Recent EVs are using new variations on lithium-ion chemistry that sacrifice specific energy and specific power to provide fire resistance, environmental friendliness, rapid charging (as quickly as a few minutes), and longer lifespans. These variants (phosphates, titanates, spinels, etc.) have been shown to have a much longer lifetime, with A123 types using lithium iron phosphate lasting at least more than 10 years and more than 7000 charge/discharge cycles, and LG Chem expecting their lithium-manganese spinel batteries to last up to 40 years.


title: Electric vehicle battery

text: Much work is being done on lithium-ion batteries in the lab. Lithium vanadium oxide has already made its way into the Subaru prototype G4e, doubling energy density. Silicon nanowires, silicon nanoparticles, and tin nanoparticles promise several times the energy density in the anode, while composite and superlattice cathodes also promise significant density improvements.


title: Electric vehicle battery

text: New data has shown that exposure to heat and the use of fast charging promote the degradation of Li-ion batteries more than age and actual use, and that the average electric vehicle battery will retain 90% of its initial capacity after six years and six months of service. For example, the battery in a Nissan Leaf will degrade twice as fast as the battery in a Tesla, because the Leaf does not have an active cooling system for its battery.


title: Electric vehicle battery

text: Non–plug-in hybrid cars have battery capacities between 0.65 kW⋅h (2012 Honda Civic Hybrid) and 1.8 kW⋅h (2001 Toyota Prius).


title: Electric vehicle battery

text: Plug-in hybrid cars have battery capacities between 4.4 kW⋅h (2012 Toyota Prius Plug-in Hybrid) and 40.6  kW⋅h (Li Auto One).


title: Electric vehicle battery

text: All-electric cars have battery capacities between 6.0 kW⋅h (2012 Renault Twizy) and 212.7 kW⋅h (2022 GMC Hummer EV).


title: Electric vehicle battery

text: In 2010, scientists at the Technical University of Denmark paid US$10,000 for a certified EV battery with 25 kWh capacity (i.e. US$400/kWh), with no rebates or surcharges. Two out of 15 battery producers could supply the necessary technical documents about quality and fire safety. In 2010 it was estimated that at most 10 years would pass before the battery price would come down to one-third.


title: Electric vehicle battery

text: According to a 2010 study, by the United States National Research Council, the cost of a lithium-ion battery pack was about /kWh of usable energy, and considering that a PHEV-10 requires about 2.0 kWh and a PHEV-40 about 8 kWh, the manufacturer cost of the battery pack for a PHEV-10 is around and it goes up to for a PHEV-40. The MIT Technology Review estimated the cost of automotive battery packs to be between to per kilowatt hour by 2020. A 2013 study by the American Council for an Energy-Efficient Economy reported that battery costs came down from /kWh in 2007 to /kWh in 2012. The U.S. Department of Energy has set cost targets for its sponsored battery research of /kWh in 2015 and /kWh by 2022. Cost reductions through advances in battery technology and higher production volumes will allow plug-in electric vehicles to be more competitive with conventional internal combustion engine vehicles. In 2016, the world had a Li-ion production capacity of 41.57 GW⋅h.


title: Electric vehicle battery

text: The actual costs for cells are subject to much debate and speculation as most EV manufacturers refuse to discuss this topic in detail. However, in October 2015, car maker GM revealed at their annual Global Business Conference that they expected a price of /kWh for Li-ion cells entering 2016, substantially lower than other analysts' cost estimates. GM also expects a cost of /kWh by the end of 2021.