UK Music is a British umbrella organisation which represents the collective interests of the production side of UK's commercial music industry: artists, songwriters, record labels, artist managers, music publishers, studio producers and music collecting societies. Launched on 26 September 2008, Feargal Sharkey, former member of The Undertones, became Chief Executive Officer and Andy Heath, former chairman of British Music Rights became chairman. Sharkey left the organisation in November 2011, with Jo Dipple taking over as Acting CEO. UK Music confirmed on 27 January 2012 the appointment of Dipple as the next CEO. In January 2017, the organisation announced that Dipple is to stand down as its CEO in June 2017. In April 2017, former Labour Party MP and Shadow Cabinet member, Michael Dugher, was announced as Dipple's replacement. Dugher took over as CEO of UK Music in May 2017. Members include the Association of Independent Music, The Ivors Academy, BPI Limited, PRS for Music, the MMF, the Music Publishers Association Limited, the Musicians Union Music Producers Guild and Phonographic Performance Limited.
The core goals of the organisation are the promotion of awareness and understanding of the following facets: The interests of the UK music industry at all levels The value of music to society and the economy Intellectual property rights and how they protect and promote creativity Opportunities and challenges for music creators in the digital age In November 2008, the magazine Music Week reported that Sharkey had written to Sir Ian Blair head of the Metropolitan Police Service, Information Commissioner Richard Thomas "to clarify the'use and purpose' of form 696, which asks for personal details on artists and musicians performing at gigs and the style of music they will be playing." In his letter, Sharkey wrote: "...the collection of this personal Data by the Met Police in advance of a musical performance is not light touch. In explicitly singling out performances and musical styles favoured by the black community: garage and R&B, MCs and DJs, we believe the use of risk assessment form 696 is disproportionate and damaging to live music in the UK."
In December 2008, UK Music launched Sound Rights, a free online resource for teachers and schools to support music study in schools. This was aimed at supporting the study of "the role of music and musicians in society, the music industry and of artistic and intellectual property rights.” In an interview with ISP Review in January 2009, UK Music Press Officer Adam Webb outlined the organisation's plans for tackling the problems of illegal file sharing over the internet and building working relationships with Internet Service Providers. In August 2018 UK Music and its members launched the #LoveMusic campaign, which sought to publicise the positive impact the European Parliament Copyright Directive would have on music creators, ahead of the vote on 12 September 2018; the campaign’s logo featured a butterfly created from a treble clef to symbolise the fragile ecosystem of the music industry, emphasising how creators needed protection or the world of music and music fans would suffer. The campaign urged people to sign a petition to be sent to MEPs.
It aimed to inform the public about how tech giants like Google and YouTube benefited from outdated copyright laws. On 6 September 2018 UK Music pulled together key industry figures and music creators outside Google’s offices in London to highlight the campaign with a busking stunt that received national media coverage. Suede frontman Brett Anderson, Blur drummer Dave Rowntree, Newton Faulkner and Ed Harcourt performed live as part of the campaign. MPs who joined the event in Kings Cross included Deputy Labour Leader and Shadow Culture Tom Watson MP, Shadow Culture Minister Kevin Brennan MP, prominent Lib Dem peer and digital economy spokesman Lord Clement-Jones, former Deputy Speaker and Conservative MP Nigel Evans. Madeleina Kay performed her song Stand Up For Your Rights outside the tech giant’s building, before a chorus of artists, led by Misty Miller and arranged by The Ivors Academy chair Crispin Hunt, performed Arcade Fire’s song Wake Up. In further support, UK Music CEO Michael Dugher wrote a piece for Record of The Day outlining UK Music’s stance on the Copyright Directive.
“When it comes to protecting the future of our music industry and start ensuring that the creators of music content get fair rewards, I hope MEPs will vote to ‘Make Google Do It,’” he wrote. On the day of the vote, UK Music’s chairman Andy Heath supported the campaign with a statement on the UK music website. UK Music celebrated Directive on Copyright in the Digital Single Market being approved on 26 March 2019 and confirmed by the Council of the European Union on 15 April 2019
26S proteasome non-ATPase regulatory subunit 5 is an enzyme that in humans is encoded by the PSMD5 gene. The 26S proteasome is a multicatalytic proteinase complex with a ordered structure composed of 2 complexes, a 20S core and a 19S regulator; the 20S core is composed of 4 rings of 28 non-identical subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides; this gene encodes a non-ATPase subunit of the 19S regulator base. The proteasome and its subunits are of clinical significance for at least two reasons: a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, they can be exploited as drug targets for therapeutic interventions.
More more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future; the proteasomes form a pivotal component for the ubiquitin–proteasome system and corresponding cellular Protein Quality Control. Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species; such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, systemic DNA damage responses leading to malignancies.
Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis, Huntington's disease, Creutzfeldt–Jakob disease, motor neuron diseases, polyglutamine diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the ubiquitin–proteasome system, the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac ischemic injury, ventricular hypertrophy and heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.
Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli in colorectal cancer, retinoblastoma. And von Hippel–Lindau tumor suppressor, as well as a number of proto-oncogenes; the UPS is involved in the regulation of inflammatory responses. This activity is attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules and prostaglandins and nitric oxide. Additionally, the UPS plays a role in inflammatory responses as regulators of leukocyte proliferation through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjögren syndrome and rheumatoid arthritis predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. PSMD5 has been shown to interact with PSMC2
The McLaren M20 was a sports prototype developed by McLaren for the 1972 season of the Canadian-American Challenge Cup. It served as a replacement for the team's M8Fs, but it became the final Can-Am design created by McLaren before the team left the series after failing to secure the 1972 championship title. M20s continued to be entered by private teams until the Can-Am championship was canceled at the conclusion of the 1974 season. McLaren driver Denny Hulme won two races during the 1972 season while Scooter Patrick won a single event in 1974 with a entered M20; when McLaren designed their replacement for 1971's M8Fs, one of the team's primary goals was to improve the cooling structure of the cars in order to allow their racing drivers, Denny Hulme and Peter Revson, more comfort during races. The M8F, as with previous McLaren sports cars, featured a large radiator mounted in the nose of the car, through which air was drawn from openings in the nose, exited upwards over the open cockpit. McLaren designers Gordon Coppuck and Tyler Alexander devised a solution to this heat problem by using two radiators, one each mounted on either side of the cockpit, drawing air from the side of the bodywork.
This meant that hot air exiting the radiator no longer passed over the cockpit, decreased fatigue on the drivers. With a radiator no longer housed in the nose of the car, McLaren designs were free to redesign the nose for better aerodynamic efficiency; this resulted in the addition of an adjustable airfoil between the front wheel fenders which increased the downforce on the front end of the car, leading to increased grip while cornering. The new radiator design required a redesign of the fuel tanks within the car; the new tanks for the M20 were compacted around the cockpit and designed to flow from the outward tanks into the central tank so that as fuel was burned off during the race, it would not affect the weight distribution of the car. The engine of the M20 was once again a Chevrolet V8 engine, increased in displacement to 509 cubic inches and producing 750 horsepower. Attached to the engine was a Hewland Mk II gearbox, mounted behind the engine rather than between the engine and cockpit as competitors Porsche and Alfa Romeo used.
The fiberglass bodywork attached to the aluminium chassis was similar to the M8F, maintaining the "Coke bottle" design, but with the addition of ducting on the side to feed the radiators. Brakes were developed in conjunction with Lockheed. Improving on the developed cross-drilled brakes from the previous season, grooves were machined into the discs to prevent outgassing. Goodyear remained as the team's official tire supplier. In total, three M20s were built by McLaren in 1972. Unlike previous McLarens, no customer variants were developed for private teams prior to McLaren leaving the Can-Am series, although all three cars were sold to other teams. Two new McLaren M20s made their debut at the inaugural round of the 1972 season; the #5 entry of Denny Hulme was able to achieve victory after some tire difficulties, beating Porsche's brand new turbocharged 917/10. Further problems appeared at Road Atlanta, where aerodynamics led to Hulme's car becoming airborne and flipping while following behind one of the Porsches.
Although Hulme's car was destroyed and had to be replaced by the third M20, Denny was able to recover and earned his second victory of the season at Watkins Glen International, followed by Revson in the other McLaren. Porsche earned their second victory in the next round, aided by rain on race day. After maintaining a close battle with Porsche in the first four races, McLaren saw the rest of the 1972 championship hopes slip away as numerous mechanical problems related to their Chevrolet motors, left them unable to finish several events. Although Hulme earned two second-place finishes at Edmonton and Riverside, it was no match for Penske-Porsche driver George Follmer. Hulme was able to maintain second place over the trouble season, but earned only half the points total that Follmer amassed. After failing to secure the Can-Am Championship for the first time since 1966, team owner Teddy Mayer decided to concentrate the company on Formula One and USAC IndyCars, leaving the Can-Am series behind.
After McLaren no longer had use for the M20s, all three were sold to separate teams. Roy Woods Racing purchased one car for driver David Hobbs to continue campaigning in Can-Am, while Fred Corbett purchased a car for Mario Andretti, replaced by John Cannon. Corbett's M20 was modified to add a turbocharger in an attempt to better match Porsche's further improved car, the 917/30; the third M20 was sold to the German Felder Racing Team for driver Helmut Kelleners, who used it in the European Interserie championship. Although none of the M20s were successful in 1973, the cars would once again be victorious during 1974. Roy Woods' M20 was sold to Herb Caplan's U. S. Racing for the 1974 Can-Am season, with driver Scooter Patrick. Patrick won the final race of the season at Road America after the dominating Shadows suffered mechanical problems; the Can-Am series would be cancelled shortly thereafter. Meanwhile, Kelleners's M20 was able to win in an Interserie event at the Nürburgring en route to finishing second in the drivers championship
David Chaim Rubinsztein FRS FMedSci is the Deputy Director of the Cambridge Institute of Medical Research, the Academic Lead of the Alzheimer's Research UK Cambridge Drug Discovery Institute, Professor of Molecular Neurogenetics at the University of Cambridge. And a UK Dementia Research Institute Professor. Rubinsztein completed his Bachelor of Medicine, Bachelor of Surgery in 1986 and PhD in 1993 in the Medical Research Council/University of Cape Town Unit for the Cell Biology of Atherosclerosis. In 1993 he went to Cambridge as a senior registrar in Genetic Pathology. In 1997, Rubinsztein acquired his Certificate of Completion of Specialist Training at the University of Cambridge, he was appointed to a Personal Readership at the University of Cambridge in 2003. In 2005, he was promoted to Professor of Molecular Neurogenetics at the University of Cambridge, he has been an author on more than 300 scientific papers, was ranked as the 4th most cited European author from 2007 to 2013 in cell biology.
Rubinsztein has been invited to give talks at major international conferences, including Gordon Research Conferences and Keystone Symposia. Rubinsztein has made major contributions to the field of neurodegeneration with his laboratory's discovery that autophagy regulates the levels of intracytoplasmic aggregate-prone proteins that cause many neurodegenerative diseases, including Huntington's, Parkinson's and Alzheimer's disease, his lab has found that autophagy may be inhibited in various neurodegenerative diseases and has elucidated the pathological consequences of autophagy compromise. In addition his research has advanced the basic understanding of autophagy, identifying the plasma membrane as a source of autophagosome membrane and characterising early events in autophagosome biogenesis. Furthermore, he studied, his goal is to understand the links between these diseases and autophagy. He is focused on understanding how to induce autophagy in vivo to remove toxic proteins and avoid the development of neurodegenerative disease Rubinsztein has won numerous awards including
Liberty Place is a skyscraper complex in Philadelphia, United States. The complex is composed of a 61-story, 945-foot skyscraper called One Liberty Place, a 58-story, 848-foot skyscraper called Two Liberty Place, a two-story shopping mall called the Shops at Liberty Place, the 14-story Westin Philadelphia Hotel. Prior to the construction of Liberty Place, there was a gentlemen's agreement not to build any structure in Center City higher than the statue of William Penn on top of Philadelphia City Hall; the tradition lasted until 1984 when developer Willard G. Rouse III of Rouse & Associates announced plans to build an office building complex that included two towers taller than City Hall. There was a great amount of opposition to the construction of the towers with critics believing breaking the height limit would lead to construction of many more tall skyscrapers, ruining the livability and charm of Center City. Despite the opposition, construction of One Liberty Place was approved and the first phase of the project began in 1985 and was completed in 1987.
One Liberty Place became the city's first skyscraper. Phase 2 of the project included Two Liberty Place, a hotel, a shopping mall, a parking garage. Construction began 1988. Construction was completed in 1990, making Two Liberty Place the second-tallest building in the city; the two towers held their place as first- and second-tallest buildings in Philadelphia until the Comcast Center was topped off in 2007. Liberty Place was received enthusiastically by critics and led to the construction of other tall skyscrapers giving Philadelphia what architecture critic Paul Goldberger called "one of the most appealing skylines of any major American city". Liberty Place was designed by his firm Murphy/Jahn; the steel and blue glass skyscrapers were influenced by New York City's Chrysler Building. The major influence is the spire made of gabled angular setbacks. Two Liberty Place's spire is shorter and squatter, a design influenced by the needs of tenant Cigna. In the 2000s, Cigna reduced its presence in the tower, which led to the owners converting the upper floors into 122 luxury condominiums.
Below the two towers is the 289 room Westin hotel and the 143,000 square feet Shops at Liberty Place. The main feature of the mall is a round atrium topped by a large glass dome. In Philadelphia, there was a gentlemen's agreement not to build any structure in Center City higher than the statue of William Penn on top of Philadelphia City Hall; the tradition lasted until the 1980s when developer Willard G. Rouse III of Rouse & Associates announced plans to build an office building complex that included two towers taller than City Hall. Prior to any development plans, Rouse wanted to acquire prime real estate in Philadelphia and he eyed a block in Center City occupied by parking lots and several small buildings; the Oliver Tyrone Pulver Corp. eyed the land for development and the company and Rouse both vied for the block of land by buying small lots throughout the site. Neither developer was able to acquire enough contiguous space to build a large office building, so after a lawsuit and failed negotiations, the two developers agreed to an organized bidding war for each other's properties.
Under the rules agreed upon, the highest bidder would get the option to buy the other's property. Rouse won the auction in 1983 for an undisclosed amount. Rouse envisioned a $US150 million 38-story skyscraper, but on April 5, 1984 Rouse announced his plans to build a complex that would include two office towers, one 65 stories the other 55 stories, a hotel, retail space. Rumors and local lore speculate Rouse spent so much money buying the land that he had to build something that justified the expense. Opposition to the project had begun before the April 5 official announcement at a Planning Commission meeting; the meeting was attended by 300 people and a number of attendees were opposed or skeptical of the idea that the skyscrapers would be taller than City Hall. Critics feared breaking the gentlemen's agreement would lead to the development of more tall skyscrapers that would end up dwarfing City Hall and changing the makeup of the city. Critic of the plan and former Philadelphia city planner Edmund Bacon said, "Once smashed, it's gone."
A phone poll conducted by the Philadelphia Daily News had callers opposing breaking the height barrier by 3,809 to 1,822. Philadelphia Inquirer editorial feared; the location of City Hall was intended as the city's center from the city's founding, critics feared taller buildings would move the city's center away from City Hall. Critics of breaking the height ceiling favored the smaller scale of the cityscape and felt that a Philadelphia with skyscrapers would affect the livability of the city. Edmund Bacon and Center City civic leaders said that Philadelphia owes its livability and charm to its low profile. Chairman of the City Planning Commission, Graham S. Finney, noted that there was a general feeling that the sky above the city was considered a public space. Supporters of breaking the height limitation noted that the project would bring needed jobs and business to Center City and that shorter buildings were blocking views of City Hall from certain directions. A planning commission meeting was held on May 3 to decide if they would approve skyscrapers that break the height limit.
Executive director of the commissioners, Barbara J. Kaplan, said the project had "substantial merit" and "that there is an opportunity here we should not pass up." She cited that the project would create US$15 million in tax revenue. Opponent Lee Copeland, dean of the University of Pennsylvani