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Chaperone (protein)

In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding and the assembly or disassembly of other macromolecular structures. Chaperones are present when the macromolecules perform their normal biological functions and have completed the processes of folding and/or assembly; the chaperones are concerned with protein folding. The first protein to be called a chaperone assists the assembly of nucleosomes from folded histones and DNA and such assembly chaperones in the nucleus, are concerned with the assembly of folded subunits into oligomeric structures. One major function of chaperones is to prevent both newly synthesised polypeptide chains and assembled subunits from aggregating into nonfunctional structures, it is for this reason that many chaperones, but by no means all, are heat shock proteins because the tendency to aggregate increases as proteins are denatured by stress. In this case, chaperones do not convey any additional steric information required for proteins to fold.

However, some specific'steric chaperones' do convey unique structural information onto proteins, which cannot be folded spontaneously. Such proteins violate Anfinsen's dogma. Various approaches have been applied to study the structure and functioning of chaperones. Bulk biochemical measurements have informed us on the protein folding efficiency, prevention of aggregation when chaperones are present during protein folding. Recent advances in single-molecule analysis have brought insights into structural heterogeneity of chaperones, folding intermediates and affinity of chaperones for unstructured and structured protein chains; some chaperone systems work as foldases: they support the folding of proteins in an ATP-dependent manner. Although most newly synthesized proteins can fold in absence of chaperones, a minority requires them for the same. Other chaperones work as holdases: they bind folding intermediates to prevent their aggregation, for example DnaJ or Hsp33. Chaperones can work as disaggregases, i.e. they can interact with aberrant protein assemblies and revent them to monomers.

Some chaperones can assist in protein degradation, leading proteins to protease systems, such as the ubiquitin-proteasome system in eukaryotes. Many chaperones are heat shock proteins, that is, proteins expressed in response to elevated temperatures or other cellular stresses; the reason for this behaviour is that protein folding is affected by heat and, some chaperones act to prevent or correct damage caused by misfolding. Macromolecular crowding may be important in chaperone function; the crowded environment of the cytosol can accelerate the folding process, since a compact folded protein will occupy less volume than an unfolded protein chain. However, crowding can reduce the yield of folded protein by increasing protein aggregation. Crowding may increase the effectiveness of the chaperone proteins such as GroEL, which could counteract this reduction in folding efficiency. More information on the various types and mechanisms of a subset of chaperones that encapsulate their folding substrates can be found in the article for chaperonins.

Chaperonins are characterized by a stacked double-ring structure and are found in prokaryotes, in the cytosol of eukaryotes, in mitochondria. Other types of chaperones are involved in transport across membranes, for example membranes of the mitochondria and endoplasmic reticulum in eukaryotes. A bacterial translocation—specific chaperone maintains newly synthesized precursor polypeptide chains in a translocation-competent state and guides them to the translocon. New functions for chaperones continue to be discovered, such as bacterial adhesin activity, induction of aggregation towards non-amyloid aggregates, suppression of toxic protein oligomers via their clustering, in responding to diseases linked to protein aggregation and cancer maintenance. Chaperones are found in, for example, the endoplasmic reticulum, since protein synthesis occurs in this area. In the endoplasmic reticulum there are general, lectin- and non-classical molecular chaperones helping to fold proteins. General chaperones: GRP78/BiP, GRP94, GRP170.

Lectin chaperones: calnexin and calreticulin Non-classical molecular chaperones: HSP47 and ERp29 Folding chaperones: Protein disulfide isomerase, Peptidyl prolyl cis-trans-isomerase, ERp57 There are many different families of chaperones. In bacteria like E. coli, many of these proteins are expressed under conditions of high stress, for example, when the bacterium is placed in high temperatures. For this reason, the term "heat shock protein" has been used to name these chaperones; the prefix "Hsp" designates. Hsp60 is the best characterized large chaperone complex. GroEL is a double-ring 14mer with a hydrophobic patch at its opening. GroES is a single-ring heptamer that binds to GroEL in the presence of ATP or ADP. GroEL/GroES may not be able to undo previous aggregation, but it does compete in the pathway of misfolding and aggregation. Acts in mitochondrial matrix as molecular chaperone. Hsp70 is the best characterized small chaperone; the Hsp70 proteins are aided by Hsp40 proteins, which increase the ATP consumption rate and activity of the Hsp70s.

It has been noted that increased expression of Hsp70 proteins in the cell results in a decrea

Harvey Girls Forever!

Harvey Girls Forever! is an American animated comedy television series produced by Brendan Hay and Aliki Theofilopoulos for DreamWorks Animation Television, is based on comic book characters from Harvey Comics. It premiered June 2018 on Netflix; the second season was released on May 10, 2019 and was retitled Harvey Girls Forever! The third season premiered on November 2019 introducing Richie Rich in the series; the fourth and final season introducing Casper the Friendly Ghost, premiered on January 10, 2020. From long kickball games through the many flavors of ice cream to an impressive climbing tree, most days on Harvey Street feels like a weekend. Audrey and Lotta are BFFs and the street's guardians, they try to start their wacky afternoon adventures. Lauren Lapkus as Lotta Stephanie Lemelin as Audrey Kelly McCreary as Dot Grey Griffin as Lucretia / Frufru / The Harvey Street Bow Atticus Shaffer as Melvin Danny Pudi as Tiny Utkarsh Ambudkar as Fredo Roger Craig Smith as Pinkeye / Bobby the Elder Jamaal Hepburn as Gerald Cree Summer as Zoe Chelsea Peretti as Maria Nat Faxon as Stu Jack Quaid as Richie Rich Bobby Moynihan as Casper Anna Camp as Chevron Dee Bradley Baker as Raccoons Chris Diamantopoulos as Additional voices Joey McIntyre, Nick Lachey, Joey Fatone, Shawn Stockman as Crush4U Music and songs are a central feature of Harvey Girls Forever! with showrunners Brendan Hay and Aliki Theofilopoulous Grafft creating a fictional boy band made up of actual boy band members to be the subject of affection for character Lotta.

“We've gotten to work... with New Kids on the Block's Joey McIntyre, Boyz II Men's Shawn Stockman, NSYNC's Joey Fatone and 98 Degrees' Nick Lachey in our Harvey Street world created boy band," said Aliki to Original songs were produced by composers Jay Ryan Lofty; as part of the promotion for Harvey Girls Forever season two the songs were made available for free download. The series premiered on Netflix on June 29, 2018. Harvey Girls Forever! on Netflix Harvey Girls Forever! at DreamWorks Harvey Girls Forever! on IMDb

Beatrice Offor

Beatrice Offor was a British painter. She is known for portraits. Offor was born in 1864 in Sydenham and trained at the Slade School of Art in London, where she became a close friend of Moina Mathers. In 1892 she married an artist and sculptor. Much of her work consisted of representations of heads of young women. A report published in 1907 said. Indeed, it may be said that Miss Beatrice Offor is one of the most popular artists of the day, her pictures are eagerly sought after, publishers vie with one another for the honour of giving her works to the public, her paintings were shown at the Royal Academy of Arts. She used her sisters as models painting brides and nude women, she painted portraits of Joseph Howard MP and Sir Ralph Littler, KC. She painted a copy of Perugino's Child for Tottenham Parish Church. For some time she was based in Chelsea – the Royal Academy catalogues give an address in the King's Road from 1899 – but following her second marriage to James Philip Beavan, a fruit importer, in 1907, she moved to Bruce Grove, Tottenham, in North London.

She suffered a nervous breakdown in 1919, died on 7 August 1920 from injuries sustained after falling from a window. A verdict of suicide while of unsound mind was returned at the inquest. 40 of her paintings are held in the collection of the Bruce Castle Museum, Tottenham. Her portrait of Sir Ralph Littler is in the Middlesex Guildhall Art Collection. Official Websitearchived at 40 paintings by or after Beatrice Offor at the Art UK site

William Martin Murphy

William Martin Murphy was an Irish businessman, newspaper publisher and politician. A member of parliament representing Dublin from 1885 to 1892, he was dubbed "William Murder Murphy" among Dublin workers and the press due to the Dublin Lockout of 1913, he was the leading promoter of tram development. Murphy was born on 6 January 1845 in Castletownbere, County Cork, educated at Belvedere College, it is incorrectly stated that he was an'only child' when in fact he had two brothers who died young, a sister Margaret Cullinane, who lived to be 93, was buried with Murphy in Glasnevin. When his father, the building contractor Denis William Murphy, died, he took over the family business, his enterprise and business acumen expanded the business, he built churches and bridges throughout Ireland, as well as railways and tramways in Britain, West Africa and South America. He was elected as Irish Parliamentary Party MP for Dublin St Patrick's at the 1885 general election, taking his seat in the House of Commons of the United Kingdom of Great Britain and Ireland.

He was a member of the informal grouping, the "Bantry band" – a group of politicians who hailed from the Bantry Bay area. The Bantry Band was disparagingly dubbed the "Pope's brass band", its most famous member was Timothy Healy MP and included Timothy Harrington MP, sometime Lord Mayor of Dublin City – however, Harrington was a Parnellite in the 1890s. When the Irish Parliamentary Party split in 1890 over Charles Stewart Parnell's leadership, Murphy sided with the majority Anti-Parnellites. However, Dublin emerged as a Parnellite stronghold and in the bitter general election of 1892, Murphy lost his seat by over three to one to a Parnellite newcomer, William Field. Murphy was the principal financial backer of the "Healyite" newspapers the National Press and the Daily Nation, his support for Healy attracted the hostility of the majority anti-Parnellite faction led by John Dillon. He made two attempts to return to Parliament, at Kerry South in 1895 and Mayo North in 1900, but both were unsuccessful because of Dillonite opposition.

In 1900, he bought the insolvent Irish Daily Independent from the Parnellites, merging it with the Daily Nation. In 1905 he re-launched this as a cheap mass-circulation newspaper, the Irish Independent, which displaced the Freeman's Journal as Ireland's most popular nationalist paper. In 1906, he founded the Sunday Independent newspaper, he refused a knighthood from King Edward VII in 1907 after organising a controversial International Exhibition in Herbert Park, Dublin. In fact, the King-Emperor, Edward VII, was about to knight Murphy. Murphy had made it clear to the viceroy, Lord Aberdeen, that under no circumstances would he accept a knighthood, but Aberdeen had failed to pass on the message. Murphy appears to have been motivated by pride. Murphy was critical of the Irish Parliamentary Party. Murphy took a benevolent attitude to traditional trade union activity amongst skilled workers, but resisted the advance of New Unionism. Worried that the I. T. G. W. U.would destroy his Dublin tram system, he led Dublin employers against the union led by James Larkin, an opposition that culminated in the Dublin Lockout of 1913.

This made him unpopular with many, being depicted as a vulture or a vampire in the workers' press. After the 1916 Easter Rising he bought ruined buildings in Abbey Street as sites for his newspaper offices; the call for the executions of Sean MacDiarmada and James Connolly at a point when the Irish public began to feel sympathy for their cause, made him more unpopular. Murphy disavowed the editorial, claiming it had been written and published without his knowledge, he was invited in 1917 to take part in talks during the Irish Convention, called to agree terms for the implementation of the suspended 1914 Home Rule Act. However he discovered that John Redmond was negotiating agreeable terms with Unionists under the Midleton Plan to avoid the partition of Ireland but at the partial loss of full Irish fiscal autonomy; this infuriated Murphy who criticised the intention in his newspaper, which damaged the Irish Parliamentary Party. However, the Convention remained inconclusive, the ensuing demise of the Irish party resulted in the rise of Sinn Féin, whose separatist policies Murphy did not agree with.

Murphy died on 26 June 1919. His family controlled Independent Newspapers until the early 1970s, when the group was sold to Tony O'Reilly. Morrissey, Thomas: William Martin Murphy, a short biography Morrissey, Thomas: Enigma of William Martin Murphy, The Irish Times, 11 September 2013. Morrissey, Thomas: William Martin Murphy: Patriotic Entrepreneur or "a soulless money-grabbing tyrant"?, History Ireland, Issue 4, Volume 21. Maume, Patrick: The Irish Independent and Empire, 1891–1919 in Simon Potter Newspapers and Empire in Ireland and Britain: Reporting the British Empire c.1857–1921 pp. 124–42. Maume, Patrick: The Irish I

Jenny (Doctor Who)

Jenny, portrayed by Georgia Tennant, is a fictional character in the long-running British science fiction television series Doctor Who. She appeared in the episode "The Doctor's Daughter" broadcast 10 May 2008. Jenny is the daughter of the series protagonist the Doctor, a product of altered DNA extracted from a tissue sample from his hand; the character was created by writer Stephen Greenhorn. Moffett is the daughter of the actor Peter Davison, who portrayed the Doctor's fifth incarnation from 1981 to 1984, she was cast as Jenny after auditioning for a more minor part in the episode "The Unicorn and the Wasp", impressing the series producers. Following the broadcast of "The Doctor's Daughter", the character was well received by reviewers, with many speculating that Jenny would return to the franchise. Moffett expressed an interest in this possibility; when the Doctor's time travelling TARDIS is drawn to the planet Messaline, his DNA is used by warring human soldiers on the planet in a Progenation Machine, a device that creates a grown and educated new person, the Doctor recognises her as his "daughter".

Born a fighter, with combat skills and tactics automatically programmed, she is ideologically at odds with the Doctor's pacifism, but after learning she has two hearts and is connected to the near-extinct race of Time Lords, she begins to pattern her behaviour on that of her father. Named "Jenny" by the Doctor's companion Donna as she is a "generated anomaly", she is received with ambivalence by the Doctor, whom she reminds of the loss of his previous family, he warms to her and welcomes her aboard his crew as a companion. Just as peace appears to have been restored between the planet's warring factions, Jenny is shot and killed; the Doctor cradles her dying form in his arms, is visibly distraught when she does not revive or regenerate from the wound. In the episode's closing scenes after the Doctor leaves, Jenny revives, takes a small spaceship, takes off into the unknown to become an explorer like her father. In the accompanying Doctor Who Confidential episode, David Tennant refers to her as "another member of that race, or something akin to it."

In the episode itself the Doctor says to Jenny, "You're an echo. A Time Lord is so much more. A sum of knowledge, a code, shared history, shared suffering", but accepts her as his daughter, saying "You're going to be more than great. Jenny's'death' is shown during "Journey's End" when the Doctor recalls those who have died while helping him, as he did not know she revived. While it is well established within Doctor Who that the Doctor once had a family—his first incarnation having travelled with his granddaughter, Susan—this fact has been referenced in the show; as executive producer Russell T Davies stated, when discussing the creation of Jenny as the Doctor's newest family member: "In the current series once or twice we've had fleeting little mentions, he said to Rose in the TARDIS in "Fear Her" that he'd been a father once. And now this story, it's not a natural, biological daughter, you could argue, but this brings him face to face with fatherhood."Regarding the creation of the character Jenny, series producer Phil Collinson explained, "It came out of a desire to keep pushing David, keep taking him in new directions, keep challenging him, really.

To find himself with a member of family is kind of one of the biggest challenges you could give him, so I'm chuffed we did it." Tennant has agreed that giving the character a daughter was "an interesting, dramatic place for the character to go," while the episode's writer, Stephen Greenhorn, has spoken of the manner in which creating Jenny allowed the show to broach "aspects of the Doctor's past life that we don't get to discuss, about his previous family that he had and lost in the Time War." Steven Moffat suggested. Before being cast as Jenny, Georgia Tennant had auditioned for a smaller role in Doctor Who episode "The Unicorn and the Wasp". Phil Collinson revealed that: "As soon as we saw her, we realised there was a much bigger and better part on in the series... so Georgia kindly waited until the time was right." Coverage of her casting focused on the fact that Moffett is the daughter of Peter Davison, who played the Doctor's fifth incarnation—as the Radio Times stated: "a Doctor's daughter is playing the Doctor's Daughter".

Moffett has described how, after Davison filmed the 2007 Children in Need segment "Time Crash", in which the Fifth Doctor returned to meet the Tenth Doctor, her father called her to inform her: "Right, now it's your go." Discussing Moffett's casting as Jenny, both actors relayed their amusement at the character's first line being "Hello, Dad," with Davison describing his own daughter playing the Doctor's daughter as "kind of surreal". He has denied that there was any nepotism involved in the casting process, explaining, "She got it off her own bat. I would love to get another part in Doctor Who, I'm not going to get her one first." Moffett has praised her character and the episode in which she appeared, asserting that: "If I'd had to write my ideal part in an episode of Doctor Who it would have been that script." She has expressed a desire to return to the role, calling on the show's producers to "Bring Jenny back. Please!" Over the course of the episode "The Doctor's Daughter", the character of Jenny undergoes marked change.

Moffett explained: "She starts off not being likeable but by the end she's learned a lot from her experiences and from The Doctor. She becomes something that he's proud of." Ini


Aeritalia was an aerospace engineering corporation based in Italy. It was formed out of the merger of two aviation companies, Fiat Aviazione and Aerfer, during 1969. Aeritalia continued several programs of its preceding companies most prominently the Fiat G.222 transport aircraft. Furthermore, the company was involved in various multinational programs and initiatives, including the European multirole aircraft Panavia Tornado, the ATR family of regional airliners, the fighter-bomber AMX International AMX. Aeritalia was a partner in the Boeing 767 from its inception, played a key role in the creation of the Italian space industry, being involved in the Alfa rocket. In 1990, Aeritalia and Selenia were merged together at the behest of parent corporation Finmeccanica to create Alenia Aeronautica, an aerospace and defense specialist. Aeritalia was created during 1969 by the merger of Fiat Aviazione's aviation businesses. In response to a NATO-issued specification for a V/STOL transport aircraft, Fiat's design team, led by Giuseppe Gabrielli, produced a design to meet this requirement, designated G.222.

According to Aeritalia, the G.222 designation is derived from the first letter of the aircraft's chief designer. The Italian Air Force, who sought a replacement for the Fairchild C-119 Flying Boxcar, felt that the G.222 proposal had merit and placed an order for two prototypes and a ground-test airframe in 1968. It was redeveloped from the NATO submission, the V/STOL lift engines were omitted and a pair of General Electric T64 turboprop engines were adopted. During December 1971, the Italian Air Force held a formal evaluation of the G.222 which led to a contract for 44 aircraft being issued to Aeritalia. In December 1975, the first production aircraft conducted its first flight. Following on from its introduction by the AMI, the G.222 was procured as a tactical transport aircraft by various international customers, including Argentina, Somalia and Thailand. In December 1978, Aeritalia elected to transfer final assembly of the G.222 from Turin to Naples, at which point a total of 44 firm orders had been obtained for the type and one aircraft per month was being manufactured.

Manufacturing of the G.222 was broken down into various companies. During early 1977, the Italian Air Force issued a requirement for 187 new-build strike fighters, which were to replace its existing Aeritalia G.91 in the close air support and reconnaissance missions, as well as the Lockheed RF-104G Starfighter being used in the reconnaissance role. Rather than competing for the contract and Italian aerospace company Aermacchi agreed to produce a joint proposal for the requirement, as both firms had been considering the development of a similar class of aircraft for some years. In April 1978, work on the joint venture formally commenced. During 1980, the Brazilian government announced that they intended to participate in the program to replace the Aermacchi MB-326. In July 1981, the Italian and Brazilian governments agreed on joint requirements, Embraer was invited to join the industrial partnership. An agreement was struck to divide AMX manufacturing between the partners. During the 1960s and 1970s, European aircraft manufacturers had, for the most part, undergone considerable corporate restructuring, including mergers and consolidations, as well as moved towards collaborative multi-national programmes, such as the newly launched Airbus A300.

In line with this trend towards intra-European cooperation, French aerospace company Aérospatiale and Aeritalia commenced discussions on the topic of working together to develop an all-new regional airliner. Prior to this, both companies had been independently conducting studies for their own aircraft concepts, the AS 35 design in the case of Aerospatiale and the AIT 230 for Aeritalia, to conform with demand within this sector of the market as early as 1978. On 4 November 1981, a formal Cooperation Agreement was signed by Aeritalia chairman Renato Bonifacio and Aerospatiale chairman Jacques Mitterrand in Paris, France; this agreement signaled not only the merger of their efforts but of their separate concept designs together into a single complete aircraft design for the purpose of pursuing its development and manufacture as a collaborative joint venture. The consortium targeted a similar unit cost but a 950 lb fuel consumption over a 200 nmi sector, nearly half the 1,750 lb required by its 40-50 seat competitors, the British Aerospace HS.748 and Fokker F.27, planned a 58-seat ATR XX stretch.

This agreement served not only as the basis and origins of the ATR company, but as the effective launch point of what would become the fledgling firm's first aircraft, designated as the ATR 42. By 1983, ATR's customer services division has been set up, readying infrastructure worldwide to provide support for ATR's upcoming aircraft to any customer regardless of location