title: William Jones (philologist)

text: Caissa has since been characterised as the "goddess" of chess, her name being used in several contexts in modern chess playing.


title: William Jones (philologist)

text: Maurice, Thomas. (1754-1824), published "An Elegiac Poem" in 1795; full title: "An Elegiac and Historical Poem: Sacred to the Memory and Virtues of the Honourable Sir William Jones. Containing a Retrospective Survey of the Progress of Science, and the Mohammedan Conquests in Asia".


title: William Jones (philologist)

text: Arthur Schopenhauer referred to one of Sir William Jones's publications in §1 of "The World as Will and Representation" (1819). Schopenhauer was trying to support the doctrine that "everything that exists for knowledge, and hence the whole of this world, is only object in relation to the subject, perception of the perceiver, in a word, representation." He quoted Jones's original English:


title: William Jones (philologist)

text: ... how early this basic truth was recognized by the sages of India, since it appears as the fundamental tenet of the Vedânta philosophy ascribed to Vyasa, is proved by Sir William Jones in the last of his essays: "On the Philosophy of the Asiatics" ("Asiatic Researches", vol. IV, p. 164): "The fundamental tenet of the Vedânta school consisted not in denying the existence of matter, that is solidity, impenetrability, and extended figure (to deny which would be lunacy), but in correcting the popular notion of it, and in contending that it has no essence independent of mental perception; that existence and perceptibility are convertible terms."


title: William Jones (philologist)

text: Schopenhauer used Jones's authority to relate the basic principle of his philosophy to what was, according to Jones, the most important underlying proposition of Vedânta. He made more passing reference to Sir William Jones's writings elsewhere in his works.


title: William Jones (philologist)

text: On 28 September 1822 the Dutch orientalist Hendrik Arent Hamaker, who accepted a professorship at the University of Leiden, gave his inaugural lecture in Latin "De vita et meritis Guilielmi Jonesii (The Life and Works of William Jones)(Leiden, 1823).


title: William Jones (philologist)

text: Edgar Allan Poe's short story "Berenice" starts with a motto, the first half of a poem, by Ibn Zaiat: "Dicebant mihi sodales si sepulchrum amicae visitarem, curas meas aliquantulum fore levatas." It was taken from the works of William Jones, and here is the missing part (from Complete Works, Vol. 2, London, 1799):


title: William Jones (philologist)

text: My companions said to me, if I would visit the grave of my friend, I might somewhat alleviate my worries. I answered "could she be buried elsewhere than in my heart?"


title: William Jones (philologist)

text: There is a statue of Jones, by the sculptor John Bacon in St Paul's Cathedral, London, erected in 1799.


title: William Jones (philologist)

text: Listing in most cases only editions and reprints that came out during Jones's own lifetime, books by, or prominently including work by, William Jones, are:


title: Swaraj

text: Swarāj ( "sva-" "self", "raj" "rule") can mean generally self-governance or "self-rule". It was first used by Chhatrapati Shivaji Maharaj to attain self rule from the Mughal Empire and the Adil Shahi and Nizam Shahi Sultanates. Later, the term was used synonymously with "home-rule" by Maharishi Dayanand Saraswati and later on by Mahatma Gandhi, but the word usually refers to Gandhi's concept of Indian independence from foreign domination. Swaraj lays stress on governance, not by a hierarchical government, but by self-governance through individuals and community building. The focus is on political decentralisation. Since this is against the political and social systems followed by Britain, Gandhi's concept of Swaraj advocated India's discarding British political, economic, bureaucratic, legal, military, and educational institutions. S. Satyamurti, Chittaranjan Das and Motilal Nehru were among a contrasting group of Swarajists who laid the foundation for parliamentary democracy in India.


title: Swaraj

text: Although Gandhi's aim of totally implementing the concepts of Swaraj in India was not achieved, the voluntary work organisations which he founded for this purpose did serve as precursors and role models for people's movements, voluntary organisations, and some of the non-governmental organisations that were subsequently launched in various parts of India. The student movement against oppressive local and central governments, led by Jayaprakash Narayan, Udit Swaraj and the Bhoodan movement, which presaged demands for land reform legislation throughout India, and which ultimately led to India's discarding of the Zamindari system of land tenure and social organisation, were also inspired by the ideas of Swaraj.


title: Swaraj

text: Swami Dayanand Saraswati, also known as Maharshi Dayanand Saraswati founder of the Arya Samaj and a Hindu reformer, defined "swaraj" as the "administration of self" or "democracy". Swami Dayanand Saraswati, beginning with the premise that God had created people free to perform any work they were inclined to choose, questioned the legitimacy of the British colonial rule in India. In the Swami's view, "swaraj" was the basis for the Indian independence movement. Dadabhai Navroji claimed that he had learnt the word "swaraj" from the "Satyarth Prakash" of Saraswati.


title: Swaraj

text: Swaraj warrants a stateless society. According to Mahatma Gandhi, the overall impact of the state on the people is harmful. He called the state a "soulless machine" which, ultimately, does the greatest harm to mankind. The purpose of the state is that it is an instrument for the service of the people. However, Gandhi feared that a state moulded with such an aim would ultimately abrogate the rights of the citizens and arrogate to itself the role of grand protector, and would demand abject acquiescence from them. This would create a paradoxical situation where the citizens would be alienated from the state and at the same time enslaved to it, which, according to Gandhi, was demoralising and dangerous. If Gandhi's close acquaintance with the working of the state apparatus in South Africa and in India strengthened his suspicion of a centralised, monolithic state, his intimate association with the Congress and its leaders confirmed his fears about the corrupting influence of political power and his scepticism about the efficacy of the party systems of power politics (due to which he resigned from the Congress on more than one occasion only to be persuaded back each time) and his study of the British parliamentary systems convinced him that representative democracy was incapable of meting out justice to people.


title: Swaraj

text: Gandhi thought it necessary to evolve a mechanism to achieve the twin objectives of empowering the people and 'empowering' the state. It was for this that he developed the two pronged strategy of resistance (to the state) and reconstruction (through voluntary and participatory social action).


title: Swaraj

text: Although the word "Swaraj" means "self-rule", Gandhi gave it the content of an integral revolution that encompasses all spheres of life: "At the individual level Swaraj is vitally connected with the capacity for dispassionate self-assessment, ceaseless self-purification and growing self-reliance." Politically, swaraj is self-government and not good government (for Gandhi, good government is no substitute for self-government) and it means a continuous effort to be independent of government control, whether it is foreign government or whether it is national. In other words, it is sovereignty of the people based on pure moral authority. Economically, Swaraj means full economic freedom for the toiling millions. And in its fullest sense, Swaraj is much more than freedom from all restraints, it is self-rule, and could be equated with "moksha" or salvation.


title: Swaraj

text: Adopting Swaraj means implementing a system whereby the state machinery is virtually nil, and the real power directly resides in the hands of people. Gandhi said: "Power resides in the people, they can use it at any time." This philosophy rests inside an individual who has to learn to be master of his own self and spreads upwards to the level of his community which must be dependent only on itself. Gandhi said: "In such a state (where swaraj is achieved) everyone is his own ruler. He rules himself in such a manner that he is never a hindrance to his neighbour." He summarised the core principle like this: "It is Swaraj when we learn to rule ourselves."


title: Swaraj

text: Gandhi was undaunted by the task of implementing such a utopian vision in India. He believed that by transforming enough individuals and communities, society at large would change. He said: "It may be taunted with the retort that this is all Utopian and, therefore not worth a single thought... Let India live for the true picture, though never realised in its completeness. We must have a proper picture of what we want before we can have something approaching it."


title: Swaraj

text: After Gandhi's assassination Vinoba Bhave formed the Sarva Seva Sangh at the national level and Sarvodya Mandals at the regional level to the carry on integrated village service — with the end purpose of achieving the goal of Swaraj. Two major nonviolent movements for socio-economic and political revolution in India: the Bhoodan movement led by Vinoba Bhave and the Total Revolution movement led by Jayaprakash Narayan were actually formed under the aegis of the ideas of Swaraj.


title: Swaraj

text: Gandhi's model of Swaraj was almost entirely discarded by the Indian government. He had wanted a system of a classless, stateless direct democracy. Yet during the Second Five-Year Plan, the Indian government initiated a hierarchy of local village leaders, called the Panchayati Raj, modified in 1992 with the intent to devolve decision-making to the villages.


title: Swaraj

text: Under Nehru India turned to a socialist model of industrial development, became a leader of non-aligned Afro-Asian countries (those refusing to side in the Cold War), and formed an alliance with the Soviet Union (although domestically firmly rejecting Marxism–Leninism). For many decades following independence English was spoken by about 2%-3% of the population, however, its use began to increase, dramatically in the 1980s. India does continue with appropriated elements of the British common law, and its rail system was built out from that left by Britain. India is a member of the British-organized Commonwealth of Nations. India successfully practices a democracy with regular elections inspired by western countries. Following Gandhi independent India worked to increase the status of women, who became citizens with the franchise and the right to divorce.


title: Swaraj

text: Organizations of Hindus, who opposed Gandhi, had also favored Swaraj. Some adopted the name Hindutva. Eventually the Bharatiya Janata Party was formed. The current leader of India is a party member, Narendra Modi.


title: Swaraj

text: The Aam Aadmi Party was founded in late 2012, by Arvind Kejriwal and some erstwhile activists of India Against Corruption movement, with the aim of empowering people by applying the concept of Swaraj enunciated by Gandhi, in the present day context by changing the system of governance.


title: County Armagh

text: County Armagh (, named after its county town, Armagh) is one of the six counties of Northern Ireland and one of the traditional thirty-two counties of Ireland. Adjoined to the southern shore of Lough Neagh, the county covers an area of and has a population of about 175,000. County Armagh is known as the "Orchard County" because of its many apple orchards. The county is part of the historic province of Ulster.


title: County Armagh

text: The name "Armagh" derives from the Irish word ' meaning "height" (or high place) and '. is mentioned in "The Book of the Taking of Ireland", and is also said to have been responsible for the construction of the hill site of (now Navan Fort near Armagh City) to serve as the capital of the kings (who give their name to Ulster), also thought to be 's "height".


title: County Armagh

text: From its highest point at Slieve Gullion, in the south of the county, Armagh's land falls away from its rugged south with Carrigatuke, Lislea and Camlough mountains, to rolling drumlin country in the middle and west of the county and finally flatlands in the north where rolling flats and small hills reach sea level at Lough Neagh.


title: County Armagh

text: County Armagh's boundary with Louth is marked by the rugged Ring of Gullion rising in the south of the county whilst much of its boundary with Monaghan and Down goes unnoticed with seamless continuance of drumlins and small lakes. The River Blackwater marks the border with County Tyrone and Lough Neagh otherwise marks out the county's northern boundary.


title: County Armagh

text: There are also a number of uninhabited islands in the county's section of Lough Neagh: Coney Island Flat, Croaghan Flat, Padian, Phil Roe's Flat and the Shallow Flat.


title: County Armagh

text: Despite lying in the east of Ireland, Armagh enjoys an oceanic climate strongly influenced by the Gulf Stream with damp mild winters, and temperate, wet summers. Overall temperatures rarely drop below freezing during daylight hours, though frost is not infrequent in the months November to February. Snow rarely lies for longer than a few hours even in the elevated south-east of the county. Summers are mild and wet and although with sunshine often interspersed with showers, daylight lasts for almost 18 hours during high-summer.


title: County Armagh

text: On 22 July 2021 the record for highest outside air temperature ever measured in Northern Ireland was set in Armagh City when a reading of 31.4° Celsius was registered at Armagh Observatory's weather station.


title: County Armagh

text: Ancient Armagh was the territory of the Ulaid (also known as Voluntii, Ultonians, Ulidians, Ulstermen) before the fourth century AD. It was ruled by the Red Branch, whose capital was Emain Macha (or Navan Fort) near Armagh. The site, and subsequently the city, were named after the goddess Macha. The Red Branch play an important role in the Ulster Cycle, as well as the Cattle Raid of Cooley. However, they were eventually driven out of the area by the Three Collas, who invaded in the 4th century and held power until the 12th. The Clan Colla ruled the area known as Airghialla or Oriel for these 800 years.


title: County Armagh

text: The chief Irish clans of the county were descendants of the Collas, the O'Hanlons and MacCanns, and the Uí Néill, the O'Neills of Fews. Armagh was divided into several baronies: Armagh was held by the O'Rogans, Lower Fews was held by O'Neill of the Fews, and Upper Fews were under governance of the O'Larkins, who were later displaced by the MacCanns. Oneilland East was the territory of the O'Garveys, who were also displaced by the MacCanns. Oneilland West, like Oneilland East, was once O'Neill territory, until it was then held by the MacCanns, who were Lords of Clanbrassil. Upper and Lower Orior were O'Hanlon territory. Tiranny was ruled by Ronaghan. Miscellaneous tracts of land were ruled by O'Kelaghan. The area around the base of Slieve Gullion near Newry also became home to a large number of the Clan McGuinness as they were dispossessed of hereditary lands held in the County Down.


title: County Armagh

text: Armagh was the seat of St. Patrick, and the Catholic Church continues to be his see. County Armagh is presently one of four counties of Northern Ireland to have a majority of the population from a Catholic background, according to the 2011 census.


title: County Armagh

text: During the 17th and 18th centuries, County Armagh was a major center of guerrilla warfare, cattle raiding, and brigandage by local Rapparees; including Count Redmond O'Hanlon, Cormacke Raver O'Murphy, and Séamus Mór Mac Murchaidh.


title: County Armagh

text: The southern part of the county has been a stronghold of support for the IRA, earning it the nickname "Bandit Country". South Armagh is predominantly nationalist, with much of the population being opposed to any form of British presence, especially that of a military nature. The most prominent opposition to British rule was the Provisional IRA South Armagh Brigade.


title: County Armagh

text: On 10 March 2009, the CIRA claimed responsibility for the fatal shooting of a PSNI officer in Craigavon, County Armagh—the first police fatality in Northern Ireland since 1998. The officer was fatally shot by a sniper as he and a colleague investigated "suspicious activity" at a house nearby when a window was smashed by youths causing the occupant to phone the police. The PSNI officers responded to the emergency call, giving a CIRA sniper the chance to shoot and kill officer Stephen Carroll.


title: County Armagh

text: The county was administered by Armagh County Council from 1899 until the abolition of county councils in Northern Ireland in 1973.


title: County Armagh

text: County Armagh remains officially used for purposes such as a Lieutenancy area – the county retains a lord lieutenant who acts as representative of the British Monarch in the county.


title: County Armagh

text: Currently the county is covered for local government purposes by four district councils, namely Armagh City and District Council, most of Craigavon Borough Council, approximately the western third of Newry and Mourne District Council and a part of Dungannon and South Tyrone Borough Council, centred around Peatlands Park.


title: County Armagh

text: Armagh ceased to serve as an electoral constituency in 1983, but remains the core of the Newry and Armagh constituency represented at Westminster and the Newry and Armagh constituency represented in the Northern Ireland Assembly. County Armagh also remains as a district for legal and property purposes; however, its baronies no longer have any administrative use.


title: County Armagh

text: The -XZ suffix is currently used on vehicle registration plates for vehicles registered in County Armagh. Other suffixes have been -IB and -LZ. These marks are followed by up to four numbers, e.g., JLZ 6789


title: County Armagh

text: County Armagh is traversed by two major highways – the M1 linking Belfast to Dungannon crosses the north of the county whilst the A1/N1 from Belfast to Dublin runs in the far south east. Other major roads in the county include the A3 and A29.


title: County Armagh

text: Armagh once had a well-developed railway network with connections to, among others, Armagh City, Culloville, Goraghwood, Markethill, Vernersbridge, Tynan (see History of rail transport in Ireland ) but today only Newry (Bessbrook), Portadown, Poyntzpass, Scarva, and Lurgan are served by rail.


title: County Armagh

text: There is a possible railway re-opening from Portadown railway station to Armagh railway station in the future. Government Minister for the Department for Regional Development, Danny Kennedy MLA indicates railway restoration plans of the line from Portadown to Armagh.


title: County Armagh

text: Ulsterbus provides the most extensive public transport system within the county, including frequent bus transfers daily from most towns to Belfast. Northern Ireland Railways / Iarnród Éireann's Enterprise service provides connections to Dublin in little over an hour and Belfast in little over forty minutes, several times daily.


title: County Armagh

text: County Armagh is traversed by the Ulster Canal and the Newry Canal which are not fully open to navigation.


title: County Armagh

text: In association football, the NIFL Premiership, which operates as the top division, has one team in the county: Glenavon, with Portadown, Annagh United, Armagh City, Dollingstown, Loughgall and Lurgan Celtic competing in the NIFL Championship, which operates as levels two and three.


title: County Armagh

text: The Armagh County Board of the Gaelic Athletic Association or Armagh GAA organises Gaelic games in the county.


title: Love the Coopers

text: Love the Coopers (titled Christmas with the Coopers in the UK and Ireland) is a 2015 American Christmas comedy-drama film directed by Jessie Nelson and written by Steven Rogers. The film stars an ensemble cast, including Alan Arkin, John Goodman, Ed Helms, Diane Keaton, Jake Lacy, Anthony Mackie, Amanda Seyfried, June Squibb, Marisa Tomei, Timothée Chalamet, Olivia Wilde and features the voice of Steve Martin, and follows a dysfunctional family who reunites for the holidays.


title: Love the Coopers

text: The film was released by CBS Films (via Lionsgate) on November 13, 2015, received negative reviews and grossed $42 million.


title: Love the Coopers

text: Sam and Charlotte are divorcing after forty years of marriage. Charlotte convinces Sam to wait until after their grown children (Hank and Eleanor), grandchildren (Hank's kids Charlie, Bo and Madison), Charlotte's father and sister (Bucky and Emma) and Sam's aunt (Fishy) have enjoyed one last "perfect Christmas" before announcing the planned divorce. As scenes shift back and forth across the Cooper family members, their memories also briefly appear on screen as younger versions of themselves.


title: Love the Coopers

text: Hank, already struggling through his recent divorce from Angie, loses his job as a family holiday photographer when replaced by a machine. Eleanor has flown in but stays in an airport bar rather than going straight to her parents’ house. She meets Joe, a soldier snowed in for at least another day at the airport. Talking about their different points of views and stances on relationships, Eleanor reveals that she is secretly dating a commitment-free married man. She hates how her parents judge her for not being in a relationship, so she convinces Joe to pretend to be her boyfriend at the family dinner.


title: Love the Coopers

text: Bucky is a regular at a local diner, where he has befriended Ruby, a 20ish waitress who is unsettled. They get into a serious argument when he learns that she is leaving town to a random spot on the map, made worse by telling others but being "too cowardly" to tell him. He then apologizes and asks her to join the family dinner. High schooler Charlie drops in on his crush, Lauren, at the holiday store she works—finally making a move and sharing a kiss with her. Emma is arrested by police officer Percy Williams after she attempts to steal a piece of jewelry as a gift for Charlotte. In his car, Emma engages him in conversation, and he relents and lets her go, with a parting advice that she buy Charlotte the most expensive thing she can afford.


title: Love the Coopers

text: Sam and Charlotte continue arguing while preparing dinner. The four generations of Coopers are arriving at the house, along with Joe, Ruby, and Hank's ex-wife, Angie. Joe mistakenly says that he and Eleanor were engaged, instead of saying that they were dating. During the dinner, chaos unleashes when Hank and Angie argue about their divorce, which leads to Bo screaming at them to "just stop fighting". There is a momentary power outage, and when it comes back Eleanor is kissing Joe, Emma is drinking everyone's wine, and Ruby screams when she sees that Bucky has collapsed.


title: Love the Coopers

text: At the hospital, Hank and Ruby walk beside Bucky's gurney as he is being taken for tests. Ruby kisses Bucky on the lips – confusing but deeply touching Hank. In the waiting room, Charlotte argues with Eleanor when she figures out that she is sleeping with Bucky's physician, Dr. Morrisey, so Eleanor crushes her further by admitting that Joe is just a prop from the airport bar whom she "invented". Alone with a sleeping Bucky in his room, Charlotte and Emma argue about their broken relationship as sisters. Joe seems to leave after also realizing Eleanor's affair is with Dr. Morrisey, but she chases after him after locking Dr. Morrisey in a room, and the two share another kiss. Charlie is surprised when Lauren appears in the waiting room, responding to the text he sent her (actually, Bo sent it to "help" him). Hank comforts Ruby as part of their budding relationship. Sam and Charlotte reconcile. Emma, following Officer Percy's advice, buys Charlotte the most expensive thing she can – a shower stool from the hospital's small gift shop. Bucky regains consciousness and walks to the hospital cafeteria, watching from a distance as everyone is happily sharing a "Christmas meal", when fortuitous muzak leads the whole Cooper clan to joyfully dance around the cafeteria.


title: Love the Coopers

text: "Love the Coopers" traces its origins to "The Most Wonderful Time", a Christmas screenplay by Steven Rogers which was then picked up by Relativity Media for a film adaptation to be directed by Jessie Nelson. Diane Keaton and Robert Redford were initially cast to star in the film, which happened to also involve producer Brian Grazer and his Imagine Entertainment company. However, on July 30, 2015, Relativity themselves filed for bankruptcy, leaving the project, now named "Love the Coopers", in limbo. Eventually, the film itself was acquired by CBS Films.


title: Love the Coopers

text: Principal photography began on December 19, 2014, in Pittsburgh, Pennsylvania, where scenes were filmed at Pittsburgh Crèche, at the U.S. Steel Tower, and at the PPG Place. Filming was also done on Ligonier Diamond in Ligonier. Filming took place at Butler Memorial Hospital in Butler, PA, in January and February 2015, and at Orchard Hill Church, during the week of February the first. Filming also took place in the residential areas of Sewickley and Edgewood, at a diner in Millvale, various areas of South Fayette, Mt. Lebanon, West Mifflin, Franklin Park, Churchill and Wilkinsburg, along with the Boyce Park Slopes. Also Pittsburgh International Airport.


title: Love the Coopers

text: "Love the Coopers" grossed $26.3 million in North America and $16.1 million in other territories for a worldwide total of $42.4 million, against a budget of $24 million.


title: Love the Coopers

text: The film opened alongside "The 33" and "My All American". In its opening weekend, it was projected to gross $6–10 million from 2,603 theaters. The film grossed $2.8 million on its opening day and $8.3 million in its opening weekend, finishing third at the box office behind "Spectre" ($33.7 million) and "The Peanuts Movie" ($24 million).


title: Love the Coopers

text: "Love the Coopers" received negative reviews from critics. On Rotten Tomatoes, the film has a rating of , based on reviews, with an average rating of . The site's consensus reads, ""Love the Coopers" has a talented cast and a uniquely bittersweet blend of holiday cheer in its better moments, but they're all let down by a script content to settle for cloying smarm." On Metacritic, the film has a score of 31 out of 100, based on 26 critics, indicating "generally unfavorable reviews". Audiences polled by CinemaScore gave the film an average grade of "B−" on an A+ to F scale.


title: Resource-based view

text: The resource-based view (RBV) is a managerial framework used to determine the strategic resources a firm can exploit to achieve sustainable competitive advantage.


title: Resource-based view

text: Barney's 1991 article "Firm Resources and Sustained Competitive Advantage" is widely cited as a pivotal work in the emergence of the resource-based view. However, some scholars argue that there was evidence for a fragmentary resource-based theory from the 1930s. RBV proposes that firms are heterogeneous because they possess heterogeneous resources, meaning firms can have different strategies because they have different resource mixes.


title: Resource-based view

text: The RBV focuses managerial attention on the firm's internal resources in an effort to identify those assets, capabilities and competencies with the potential to deliver superior competitive advantages.


title: Resource-based view

text: During the 1990s, the "resource-based view" (also known as the "resource-advantage theory") of the firm became the dominant paradigm in strategic planning. RBV can be seen as a reaction against the positioning school and its somewhat prescriptive approach which focused managerial attention on external considerations, notably industry structure. The so-called positioning school had dominated the discipline throughout the 1980s. In contrast, the resource-based view argued that sustainable competitive advantage derives from developing superior capabilities and resources. Jay Barney's 1991 article, "Firm Resources and Sustained Competitive Advantage," is seen as pivotal in the emergence of the resource-based view.


title: Resource-based view

text: A number of scholars point out that a fragmentary resource-based perspective was evident from the 1930s, noting that Barney was heavily influenced by Wernerfelt's earlier work which introduced the idea of resource position barriers being roughly analogous to entry barriers in the positioning school. Other scholars suggest that the resource-based view represents a new paradigm, albeit with roots in "Ricardian and Penrosian economic theories according to which firms can earn sustainable supranormal returns if, and only if, they have superior resources and those resources are protected by some form of isolating mechanism precluding their diffusion throughout the industry." While its exact influence is debated, Edith Penrose's 1959 book "The Theory of the Growth of the Firm" is held by two scholars of strategy to state many concepts that would later influence the modern, resource-based theory of the firm.


title: Resource-based view

text: The RBV is an interdisciplinary approach that represents a substantial shift in thinking. The resource-based view is interdisciplinary in that it was developed within the disciplines of economics, ethics, law, management, marketing, supply chain management and general business.


title: Resource-based view

text: RBV focuses attention on an organisation's internal resources as a means of organising processes and obtaining a competitive advantage. Barney stated that for resources to hold potential as sources of sustainable competitive advantage, they should be valuable, rare, imperfectly imitable and not substitutable (now generally known as "VRIN" criteria). The resource-based view suggests that organisations must develop unique, firm-specific core competencies that will allow them to outperform competitors by doing things differently.


title: Resource-based view

text: Although the literature presents many different ideas around the concept of the resource-advantage perspective, at its heart, the common theme is that the firm's resources are financial, legal, human, organisational, informational and relational; resources are heterogeneous and imperfectly mobile and that management's key task is to understand and organise resources for sustainable competitive advantage. Key theorists who have contributed to the development of a coherent body of literature include Jay B. Barney, George S. Day, Gary Hamel, Shelby D. Hunt, G. Hooley and C.K. Prahalad.


title: Resource-based view

text: Achieving a sustainable competitive advantage lies at the heart of much of the literature in strategic management and strategic marketing. The resource-based view offers strategists a means of evaluating potential factors that can be deployed to confer a competitive edge. A key insight arising from the resource-based view is that not all resources are of equal importance, nor do they possess the potential to become a source of sustainable competitive advantage. The sustainability of any competitive advantage depends on the extent to which resources can be imitated or substituted. Barney and others point out that understanding the causal relationship between the sources of advantage and successful strategies can be very difficult in practice. Thus, a great deal of managerial effort must be invested in identifying, understanding and classifying core competencies. In addition, management must invest in organisational learning to develop, nurture and maintain key resources and competencies.


title: Resource-based view

text: In the resource-based view, strategists select the strategy or competitive position that best exploits the internal resources and capabilities relative to external opportunities. Given that strategic resources represent a complex network of inter-related assets and capabilities, organisations can adopt many possible competitive positions. Although scholars debate the precise categories of competitive positions that are used, there is general agreement, within the literature, that the resource-based view is much more flexible than Porter's prescriptive approach to strategy formulation.


title: Resource-based view

text: Given the centrality of resources in terms of conferring competitive advantage, the management and marketing literature carefully defines and classifies resources and capabilities.


title: Resource-based view

text: Barney defines firm resources as: "all assets, capabilities, organizational processes, firm attributes, information, knowledge, etc. controlled by a firm that enable the firm to conceive of and implement strategies that improve its efficiency and effectiveness"


title: Resource-based view

text: Capabilities are "a special type of resource, specifically an organizationally embedded non-transferable firm-specific resource whose purpose is to improve the productivity of the other resources possessed by the firm."


title: Resource-based view

text: Barney defined a competitive advantage as "when [a firm] is able to implement a value creating strategy not simultaneously being implemented by any current or potential competitors."


title: Resource-based view

text: While RBV scholars have traditionally focused on intraorganizational resources and capabilities, some research points to the importance of interorganizational routines. Routines between organizations and the ability to manage interorganizational relationships can improve performance. Such collaboration capabilities are, in particular, supported by contract design capabilities.


title: Resource-based view

text: Firms in possession of a resource, or mix of resources that are rare among competitors, are said to have a "comparative advantage." This comparative advantage enables firms to produce marketing offerings that are either (a) perceived as having superior value or (b) can be produced at lower costs. Therefore, a comparative advantage in resources can lead to a competitive advantage in market position.


title: Resource-based view

text: In the resource-based view, strategists select the strategy or competitive position that best exploits the internal resources and capabilities relative to external opportunities. Given that strategic resources represent a complex network of inter-related assets and capabilities, organisations can adopt many possible competitive positions. Although scholars debate the precise categories of competitive positions that are used, there is general agreement, within the literature, that the resource-based view is much more flexible than Porter's prescriptive approach to strategy formulation. Hooley et al. suggest the following classification of competitive positions:


title: Resource-based view

text: In addition to the resource-based views, value-based views provide an additional way to create organizational management links between employees at a company, based on their core values and beliefs.


title: Resource-based view

text: The main reason for these alternate steps to view strategy is to provide a method that concentrates on the values of management practices, rather than simply resourced-based strategy.


title: Sinitta

text: Sinitta Malone (born 19 October 1963), known mononymously as Sinitta, is an American-born British singer, actress and television personality. She initially found commercial success in the mid-1980s with the single "So Macho" and had several other hits during the decade. In the 2000s, she became known for television appearances, including "Loose Women", "The Xtra Factor" and "This Morning". She took part in the ITV show "I'm a Celebrity... Get Me Out of Here!" in 2011.


title: Sinitta

text: She was born in Seattle, Washington. Sinitta's mother is Miquel Brown, who was a popular Canadian disco-soul singer in the 1970s and 1980s and a member of the cast of "Hair" who gave birth to her when she was only 14 years old; her father is Anthony. She has a sister Gretta who was adopted by a relative. Sinitta was born and raised in Seattle and later Detroit, but frequently travelled with her mother on tour including to Sydney. Her mother then directed the London production of "Hair"; Sinitta was sent to boarding school in East Sussex, and ballet school in Tunbridge Wells from the age of 9. She auditioned for musical roles in London, performing in "The Wiz" at age 12 while still in school.


title: Sinitta

text: In 1981, Sinitta appeared in the film "Shock Treatment" as Frankie, credited as Sinitta Renet. Sinitta continued her career by appearing in several West End productions, notably the first production of the Andrew Lloyd Webber musical "Cats". She also later appeared in "Little Shop of Horrors".


title: Sinitta

text: In 1986, Sinitta released the single "So Macho", which debuted at 59 on the UK charts; the single remained rather low in the charts but, later that year, reached number 16, climbing to number 5 the following week. The subsequent week, "So Macho" reached number 2 in the UK, scoring its highest position on the charts and also giving Sinitta her first Top 3 charting single. "So Macho" spent the following six weeks in the Top 20 in the UK. Alongside this success in the UK, "So Macho" also reached the Top 20 in Sweden, Australia and Austria. "So Macho" subsequently became the highest-charting of Sinitta's career to date. Sinitta's second single "Feels Like the First Time" was far less commercially successful, charting at number 45. In 1987, Sinitta released the lead single from her upcoming debut album, after seeking the help of rising super-producers Stock Aitken Waterman (SAW). The product of that collaboration, "Toy Boy", was based on a tabloid headline about Sinitta's love life, and featured a rap written by the singer. It debuted at number 41 and climbed to number 4 in the UK, where it remained for three consecutive weeks. The single remained in the Top 20 for eight weeks. The track also reached number 3 in Switzerland, reaching the Top 20 in Ireland, Belgium, Sweden, Finland and Germany. Sinitta then released the second single from the album, "GTO"; the single reached number 15 on the UK chart. "GTO" also became Sinitta's first hit in Spain, reaching number 3. The track reached number 11 in Switzerland, number 9 in Norway and number 13 in Ireland. The success of the track came despite the singer initially expressing her dissatisfaction with the subject matter of the song when first presented with the idea by record label boss, Simon Cowell. Fearing that the title would mean nothing to her core audience of gay men and younger record buyers, Sinitta had unsuccessfully begged producers Stock Aitken Waterman to retitle the track before recording. Sinitta later released her debut album "Sinitta!", which performed moderately, charting at number 34 in the UK. This album also reached number 69 in Australia.


title: Sinitta

text: In 1988, Sinitta released "Cross My Broken Heart", taken from "Sinitta!", which reached number 6 in the UK and number 7 in Ireland. The track charted at number 12 in Spain, becoming her second Top 20 single in Spain. Sinitta then released "I Don't Believe In Miracles", which reached number 22 in the UK.


title: Sinitta

text: In 1989, Sinitta moved away from working directly with producers Stock Aitken Waterman amid creatives differences and the producers' changing priorities following the rise of their in-house superstar Kylie Minogue. However, Sinitta did continue to work with Pete Hammond, Phil Harding and Ian Curnow with PWL, in co-operation with German producer Ralf-René Maué who was responsible for such hits of the Hamburg-based eurodisco duo London Boys as "Harlem Desire'", "Requiem" and "London Nights". The second album was confirmed as "Wicked". The lead single of the album was "Right Back Where We Started From", which debuted at number 19 in the UK and rose to number 6. The following week the track climbed to number 4 in the UK, holding this position for the subsequent week. For the subsequent four weeks, the single remained in the Top 40. It also charted across the rest of Europe, notably reaching number 7 in Finland and the Top 40 in Denmark, Spain and Germany. "Right Back Where We Started From" also charted successfully in Oceania, reaching number 7 in Australia and number 2 in New Zealand, thus becoming her highest charting single in both countries. In addition to this success, the track made the year-end charts, at number 45 in Australia, number 38 in New Zealand and number 49 in the UK. As a follow-up single, Sinitta released "Love on a Mountain Top", which charted at number 20 in the UK and number 81 in Australia.


title: Sinitta

text: The final lead single of the album, however, was the least successful out of the three, failing to chart at all. In 1990, Sinitta released the single "Hitchin' a Ride", which performed moderately, charting at number 20 in the UK, whilst "Love and Affection" peaked at number 62.


title: Sinitta

text: The following April, Sinitta released the single "The Supreme (EP)", a 4 track EP containing covers of 4 songs originally by The Supremes which charted at number 49 in the UK. In 1995, Sinitta released a covers album called "Naughty Naughty", which was also the only album of hers to be released in Asia.


title: Sinitta

text: She appeared on the cast recording album for "What a Feeling", a live recording taken from the Apollo Playhouse Theatre, Edinburgh, in May 1997, and replaced Irene Cara to tour with Sonia (a fellow former SAW artist) and Luke Goss (formerly of Bros) in the rock and pop musicals concert, "What a Feeling" the same year.


title: Sinitta

text: In 1997, Sinitta recorded vocals for a cover of the Limme & Family Cookin' hit "You Can Do Magic" with Mike Stock and Matt Aitken, believing it to be her comeback single. However, the track was in fact an elaborate stunt by TV show The Cook Report, which aimed to expose alleged chart rigging by attempting to hype the track into the charts. The record was fronted by reporter Debbie Currie, who pretended to sing to Sinitta's vocal. The first Sinitta knew about it was when the show was aired, leaving her feeling used and betrayed.


title: Sinitta

text: In 2004, Sinitta made her premiere appearance on "The X Factor" in the first series, when she assisted Simon Cowell at the Judges' Houses stage, helping to select his final three acts for the live show, with the eventual winner being Steve Brookstein. In 2005, Sinitta helped Cowell once more, this time choosing the final three groups. In 2006, she helped Cowell select Leona Lewis, who became the second winner chosen by them, with Lewis becoming one of the most successful acts from the show. In 2009, Sinitta returned to the show again for the Judges' Houses stage, and then helped to choose Olly Murs. In 2007, Sinitta became a judge on the ITV show "Grease Is the Word".


title: Sinitta

text: The following year, Sinitta joined the cast of the daytime ITV show "Loose Women" as a presenter. In 2010, Sinitta helped Cowell again by choosing One Direction who have since become the biggest act to have come out of the "X Factor". In 2011, however, Sinitta assisted Louis Walsh for the first time, rather than Cowell. In November that year, Sinitta was confirmed to be taking part in the eleventh series of "I'm a Celebrity, Get Me Out of Here!" as one of the contestants and would be entering the jungle on Day 3.


title: Sinitta

text: In 2013, Sinitta helped Walsh to select Nicholas McDonald, who eventually finished second. That same year, she appeared in the music video for a cover of the 1980s hit "Take On Me" on Children in Need. In December, she appeared on "Celebrity Come Dine with Me", alongside Danniella Westbrook, Louie Spence and Hugo Taylor.


title: Sinitta

text: The following year, Sinitta was announced as joining the cast of the new upcoming Channel 4 reality TV show "The Jump". Sinitta was eliminated fourth overall, placing seventh.


title: Sinitta

text: Sinitta returned to her music career in 2014, with her comeback single being "So Many Men, So Little Time". She later performed the single at "Pride in London". Sinitta returned to assist Simon Cowell again that year, when she helped to choose Fleur East and Ben Haenow, who came second and won the show respectively.


title: Sinitta

text: In 2009, Sinitta became one of the main presenters on "The Xtra Factor", on which she interviewed the contestants' friends and family. In 2011, she returned to the show during the live show stages as one of the presenters who visited the finalists' home towns. Her segment on the show became regular, and carried on into 2012 and subsequently 2013 and 2014. In 2016, she was announced as the producer and one of the lead presenters of the "Xtra Factor"; she stated that she had "revamped" the whole show.


title: Sinitta

text: Sinitta appeared in the hit reality TV show "Ant & Dec's Saturday Night Takeaway" as a recurring character in 2016. Alongside this, Sinitta became a series regular on the chat show "Up Late with Rylan", and also made appearances on "Celebrity Masterchef" as a contestant, although she was eliminated in Week 1.


title: Sinitta

text: In October 2021, Sinitta announce the release of her first Christmas track, "I Won't Be Lonely This Christmas", scheduled for release on 3 December 2021.


title: Sinitta

text: Sinitta appeared as Kangaroo in an "I'm a Celebrity...Get Me Out of Here!" special episode of "The Masked Singer".


title: Sinitta

text: Sinitta was married from 2002 to 2010 to Andy Willner, and has two adopted children. A series of autobiographical videos document her life, and a book is due to follow. Her past relationships and documentation of sexual assaults received media attention in 2018.


title: Poise (unit)

text: The poise (symbol P; ) is the unit of dynamic viscosity (absolute viscosity) in the centimetre–gram–second system of units (CGS). It is named after Jean Léonard Marie Poiseuille (see Hagen–Poiseuille equation). The centipoise (1 cP = 0.01 P) is more commonly used than the poise itself.


title: Poise (unit)

text: The poise is often used with the metric prefix "centi-" because the viscosity of water at 20 °C (standard conditions for temperature and pressure) is almost exactly 1 centipoise. A centipoise is one hundredth of a poise, or one millipascal-second (mPa⋅s) in SI units (1 cP = 10 Pa⋅s = 1 mPa⋅s).


title: Poise (unit)

text: Liquid water has a viscosity of 0.00890 P at 25 °C at a pressure of 1 atmosphere (0.00890 P = 0.890 cP = 0.890 mPa⋅s).


title: Oberammergau

text: Oberammergau is a municipality in the district of Garmisch-Partenkirchen, in Bavaria, Germany. The small town on the Ammer River is known for its woodcarvers and woodcarvings, for its NATO School, and around the world for its 380-year tradition of mounting Passion Plays.


title: Oberammergau

text: The Oberammergau Passion Play was first performed in 1634. According to local legend, the play is performed every ten years because of a vow made by the inhabitants of the village that if God spared them from the effects of the bubonic plague then sweeping the region, they would perform a passion play every ten years. A man traveling back to the town for Christmas allegedly brought the plague with him by accident. The man purportedly died from the plague and it began spreading throughout Oberammergau. After the vow was made, according to tradition, not another inhabitant of the town died from the plague. All of the town members that were still suffering from the plague are said to have recovered.


title: Oberammergau

text: The play is now performed in years ending with a zero, as well as in 1934 which was the 300th anniversary and 1984 which was the 350th anniversary (though the 1920 performance was postponed to 1922 due to postwar economic conditions, and the 1940 performance was cancelled due to the onset of the Second World War in 1939). The 2020 play is being postponed to 2022 due to the outbreak of COVID-19. It involves over 2000 actors, singers, instrumentalists and technicians, all residents of the village.


title: Oberammergau

text: The name of the village (as well as that of neighbouring Unterammergau) appears in a well-known German tongue-twister, often sung as a round:


title: Oberammergau

text: Over 2,000 villagers performed the story of the Passion of Jesus for the audiences from around the world. This was a labor-intensive community enterprise, in which only natives of the village could participate. Performances have taken place between mid-May and early October.


title: Oberammergau

text: The play has a major economic impact on Oberammergau. There is a local expression ""Die Passion zahlt"" ("The Passion Play will pay for it") in explaining how the Oberammergau community financed construction of a new community swimming pool, community centre, and other civic improvements. Since 1930, the number of visitors has ranged from 420,000 to 530,000. Most tickets are sold as part of a package with one or two nights' accommodation.


title: Oberammergau

text: The village is also known as the home of a long tradition of woodcarving; the Bavarian State Woodcarving School is located there. Among the celebrated former students is the German artist Wolfram Aichele. His processional church staff depicting Christ on a donkey can be seen in the church of St Peter and St Paul. The streets of central Oberammergau are home to dozens of woodcarver shops, with pieces ranging from religious subjects, to toys, to humorous portraits.


title: Oberammergau

text: Oberammergau is also famous for its "Lüftlmalerei," or frescoes, of traditional Bavarian themes, fairy tales, religious scenes or architectural "trompe-l'œil" found on many homes and buildings. Lüftlmalerei is common in Upper Bavaria and its name may be derived from an Oberammergau house called "Zum Lüftl", which was the home of facade painter Franz Seraph Zwinck (1748–1792).


title: Oberammergau

text: The village is also known for its religious art. A wooden statue of Our Lady of Good Voyage from Oberammergau stands in the Seaport Shrine in Boston, Massachusetts.


title: Oberammergau

text: Oberammergau lies near the Bundesstraße 23, part of the "Deutsche Alpenstrasse" route. Its single-track, single platform railway station is the terminus of the Ammergau Railway. Several Aerial lifts climb the nearby mountains.


title: Oberammergau

text: The Conrad von Hötzendorf Kaserne was built just east of the village in 1935–37 as a base for the signals detachment ("Gebirgs-Nachrichten-Abteilung 54)" of the Mountain Brigade. In October 1943, the barracks were taken over by the Messerschmitt company as a research and development site; of tunnels were bored into the neighboring Laber mountain for engine production facilities, and a winter sports hotel was also taken over. In all, Messerschmitt had 500 employees in the design department and about 1,300 more in the factory. At the end of the Second World War, the Messerschmitt design department was visited by both U.S. and British scientific missions, as well as by teams from Bell (who stayed for five weeks) and de Havilland. Among the German staff interviewed by the Fedden Mission were Woldemar Voigt, Messerschmitt's chief designer, Hans Hornung, and Joseph Helmschrott.


title: Oberammergau

text: After the war, the Americans occupied the kaserne, renaming it Hawkins Barracks and making it the primary facility of U.S. Army School Europe; over the next three decades schools in specialties ranging from military police to nuclear weapons handling were located there. The base reverted to German Army control and its original name in 1974.


title: Oberammergau

text: NATO School, formerly NATO Weapons Systems School, the alliance's principal training and education facility on the operational level, has been located at Hawkins Barracks/Hötzendorf Kaserne since 1953.


title: Letter of recommendation

text: A letter of recommendation or recommendation letter, also known as a letter of reference, reference letter or simply reference, is a document in which the writer assesses the qualities, characteristics, and capabilities of the person being recommended in terms of that individual's ability to perform a particular task or function. Letters of recommendation are typically related to employment (such a letter may also be called an employment reference or job reference), admission to institutions of higher education, or scholarship eligibility. They are usually written by someone who worked with or taught the person, such as a supervisor, a colleague or teacher.


title: Letter of recommendation

text: References may also be required of companies seeking to win contracts, particularly in the fields of engineering, consultancy, industry and construction, and with regard to public procurement and tenders. Reference letters for organizations are used to assess its ability to deliver the required level of service.


title: Letter of recommendation

text: The person providing a reference is called a referee. An employment reference letter is usually written by a former employer or manager, but references can also be requested from co-workers, customers and vendors. Teachers and professors often supply references for students who have taken their classes. Reference letters for organizations are usually supplied by parties to which the company has provided similar services in the past.


title: Letter of recommendation

text: In some countries, elements of performance are evaluated using established forms of expression, sometimes euphemistic. For example, in the German-language "Arbeitszeugnis", the following terms are frequently used:


title: Letter of recommendation

text: This language established itself as an unwritten code in the employment world. Its purpose was to give even weakly performing employees a letter of recommendation that does not sound negative. However, the euphemistically glazed-over descriptions are now codified and generally known, so that the original cryptic intent is no longer served. Nonetheless, it is still standard to use this codified language.


title: Letter of recommendation

text: For example, a German "Arbeitszeugnis" is usually issued automatically to a leaving employee, and is therefore not addressed to a particular requester. A letter of recommendation for a university of college in the USA is usually written for and addressed to a specific institution the student wants to apply to.


title: Letter of recommendation

text: If the letter is specifically addressed to a particular requester, the letter will often be sent directly to that requester, and not to the applicant. In that case, applicants usually have the right to view a copy of the letter. Some applications, such as professional schools give applicants the choice to waive their right to view their letters. Usually, applicants are encouraged to waive their rights because if they do not, it is a sign they are not confident in their recommenders.


title: Letter of recommendation

text: Most potential employers will contact referees to obtain references before offering a job to a new employee. A survey by the Society for Human Resource Management (SHRM) found that eight out of ten resource professionals said they regularly conduct reference checks for professional (89%), executive (85%), administrative (84%) and technical (81%) positions. Candidates are advised to ensure that they provide a suitable list of referees to their new prospective employer or institution, and to contact those referees to ensure that they are able and willing to provide a suitable reference. In some cases employers will contact a candidate's former company for a reference even if no contact is supplied by the candidate.


title: Letter of recommendation

text: Some employers may not be willing to provide reference letters because they may be worried about potential lawsuits. In this case, the employer may only provide the job title, dates of employment and salary history for the employee. Finland, Germany, Austria, Switzerland, Hungary and Bulgaria are the only countries in Europe where employees can legally claim an employment reference, including the right to a correct, unambiguous and benevolent appraisal.


title: Letter of recommendation

text: While there is no common law duty to provide a reference, the Supreme Court of Canada has held that a refusal to do so may constitute "conduct that is unfair or is in bad faith" with respect to a wrongful dismissal, and thus "indicative of the type of conduct that ought to merit compensation by way of an addition to the notice period." There is a duty of care to ensure that, where one is provided, it is accurate and fair and not give a misleading impression, as held by the House of Lords in "Spring v Guardian Assurance plc". If an employer goes beyond what a reference should contain, or if it gives inaccurate or misleading information, liability may arise in the areas of breach of statutory duty, negligent misstatement, deceit, defamation or malicious falsehood. It does not matter what form the reference might take.


title: Letter of recommendation

text: In the United Kingdom, references received by an employer from another person or organization can be disclosed to the person about whom they are written under the subject access provisions of the Data Protection Act 1998, but certain confidentiality considerations apply as to the identity of the person giving the reference. As a result, together with the duty of care under "Spring", many organizations have issued guidance as to best practice to be undertaken by reference providers.


title: Letter of recommendation

text: The duty of care has also been held to apply in non-reference situations, as noted in 2011 in " McKie v Swindon College". In another case, the Court of Appeal of England and Wales has held that "a reference must not give an unfair or misleading impression overall, even if its discrete components are factually correct." However, while a reference must be accurate and fair, it is not necessary to report all material facts concerning an individual, but it can be argued that, if an agreed reference arising from a settlement agreement is misleadingly incomplete, the employer can be sued by a subsequent employer for breaching its duty of care. The Employment Appeal Tribunal, in an unfair dismissal case, ruled that, in preparing a reference, it was not reasonable to provide details of complaints against an employee of which the employee was not aware.


title: Letter of recommendation

text: The Court of Appeal has further held that, if an employee leaves when an investigation is ongoing but has not been concluded, or where issues arise after an employee leaves that have not been investigated, employers can disclose this information but should do so in a measured and fair way, which will be particularly important if to omit this information would mean providing a misleading reference.


title: Letter of recommendation

text: In 2014, the UK government's Crown Commercial Service issued an information note clarifying that government departments are permitted to issue references relating to suppliers, and that failure to do so, reflecting a belief that policy matters prevented references from being issued, could have a detrimental effect on companies' development, especially small and medium sized enterprises. The information note emphasised the importance of references being based on evidence and contemporaneous records, related to a specific proposed contract for which a reference has been requested, and issued by a member of staff formally authorised to speak for the organisation providing the reference.


title: Letter of recommendation

text: In 2016, the Financial Conduct Authority and the Prudential Regulation Authority are issuing rules that will require the furnishing of references, before any approval or certification may be given by them, as well as specifying the information that they must contain.


title: Letter of recommendation

text: In India, employees typically receive a relieving letter (also called an experience certificate or service certificate) from their employer when leaving a job. While the relieving letter may also serve as a letter of recommendation, the specific purpose of the relieving letter is to prove to any new employer that the applicant properly resigned from their old job and fulfilled all obligations to the old employer, such as working the notice period.


title: Letter of recommendation

text: Generally, employers are legally required to provide a relieving letter to leaving employees. In Kerala for example this is regulated in the Kerala Shops and Commercial Establishments Bill Despite this, employers will sometimes deny or delay providing a relieving letter, which makes it difficult for a leaving employee to start a new job.


title: Vladimir Kara-Murza

text: Vladimir Vladimirovich Kara-Murza (; born 7 September 1981) is a Russian political activist, journalist, author, and filmmaker. A protégé of Boris Nemtsov, he serves as vice-chairman of Open Russia, an NGO founded by Russian businessman and former oligarch Mikhail Khodorkovsky, which promotes civil society and democracy in Russia. He was elected to the Coordinating Council of the Russian Opposition in 2012, and served as deputy leader of the People's Freedom Party from 2015 to 2016. He has directed two documentaries, "They Chose Freedom" and "Nemtsov". As of 2021, he acts as Senior Fellow to the Raoul Wallenberg Centre for Human Rights. He was awarded the Civil Courage Prize in 2018.


title: Vladimir Kara-Murza

text: In April 2022, Kara-Murza was arrested on charges of disobeying police orders; later his arrest was extended after new charges of "discrediting" the military were introduced, and in October, new charges of treason were reportedly introduced against him.


title: Vladimir Kara-Murza

text: Vladimir Vladimirovich Kara-Murza was born in Moscow on 7 September 1981. He is the son of Russian journalist and television host Vladimir Alexeyevich Kara-Murza (1959–2019), an outspoken critic of Leonid Brezhnev and a supporter of reforms under Boris Yeltsin. His father was a great-grandson of Latvian revolutionary Voldemārs Bisenieks (1884–1938), and great-grand-nephew of Latvia's first Ambassador to Great Britain, Georgs Bisenieks (1885–1941; ), both of whom were shot by the NKVD. The Latvian agronomist and publisher Jānis Bisenieks (1864–1923; ) was their older brother.


title: Vladimir Kara-Murza

text: He is also related to Sergey Kara-Murza (born 1939), a Soviet/Russian historian, chemist and philosopher. They are members of the Kara-Murza family, descendants of a Tatar aristocrat who settled in Moscow and converted to Christianity in the 15th century AD. (The name in translation means "Black Lord".)


title: Vladimir Kara-Murza

text: Kara-Murza earned a BA and an MA degree in history at Cambridge University. With his wife, Yevgenia, he has three children.


title: Vladimir Kara-Murza

text: Kara-Murza became a journalist at the age of 16. He worked as London correspondent for a succession of Russian media outlets: the newspapers "Novye Izvestia" (1997–2000) and "Kommersant" (September 2000 to June 2003) and the radio station "Ekho Moskvy" from September 2001 to June 2003. Kara-Murza then briefly became foreign affairs correspondent of "Kommersant" (July 2003 to April 2004) and Washington correspondent for the BBC (December 2004 to December 2005). In 2002, he was editor-in-chief of the London-based financial publication "Russian Investment Review". In April 2004 he took over as the Washington bureau chief of the RTVi television network, a post he held for the next nine years. On 1 September 2012 he was dismissed from this job.


title: Vladimir Kara-Murza

text: In 2005, Kara-Murza produced a four-part TV documentary, "They Chose Freedom", dedicated to the history of the Soviet dissident movement. The documentary was based on interviews with Russian dissidents, including Vladimir Bukovsky, Elena Bonner and Sergei Kovalev. It was first aired in October 2005.


title: Vladimir Kara-Murza

text: It has since been screened at various locations in Europe and North America, with subtitles added in English. On 24 March 2014, Kara-Murza, Anne Applebaum, and Vladimir Bukovsky took part in a discussion following a London screening of the film.


title: Vladimir Kara-Murza

text: In 2011, Kara-Murza published his first book, "Reform or Revolution: The Quest for Responsible Government in the First Russian State Duma" (in Russian only), which recounts the unsuccessful attempt by the Cadets or Constitutional Democratic Party to form a government during the brief existence of the first Russian Parliament or Duma from April to July 1906. Based on the original 1906 parliamentary record and contemporary newspaper reports, as well as memoirs by participants of the events, the book was launched in both Moscow and Saint Petersburg.


title: Vladimir Kara-Murza

text: In late 2014 and early 2015, he wrote about a number of anti democratic trends in Russia. President Vladimir Putin, for example, had resumed the Soviet practice of stripping dissidents of their Russian citizenship. As a result of this and other acts, Kara-Murza urged the Council of Europe not to restore Russia's voting rights, suspended since the annexation of Crimea. Kremlin SWAT teams, he wrote in December 2014, were breaking up opposition meetings. Putin's word was therefore "void of value", wrote Kara-Murza, citing as evidence the false statements made by the Russian President and his broken promises.


title: Vladimir Kara-Murza

text: Putin had soft-pedaled his response to the opposition during the Sochi Olympics, warned Kara-Murza in an op-ed for "The Wall Street Journal" (26 February 2014). Now that the prestigious international event was ended the Russian president was rapidly returning to his former oppressive behaviour. Only hours after the closing ceremony in Sochi a Moscow court handed prison sentences to seven of the May 2012 Bolotnaya Square protestors.


title: Vladimir Kara-Murza

text: Pressure was brought to bear not only within Russia. Russia's nationwide TV had been broadcasting "hate-filled appeals to crush the protesters in Kiev" for several weeks early in 2014, noted Kara-Murza. For Putin, he explained, "maintaining the status quo in Ukraine was not primarily about preserving a post-Soviet sphere of influence or recreating a Moscow-led empire". The Russian president feared that "a democratic, pro-European Ukraine" would set "a 'dangerous' precedent for Russia" and that it would be "only a matter of time" before Russian citizens began to demand similar levels of political and economic freedom.


title: Vladimir Kara-Murza

text: From 1999 to 2001, Kara-Murza was a member of the Democratic Choice of Russia party; from 2001 to 2008 he was a member of the Union of Right Forces. Between 2000 and 2003 he served as an advisor to State Duma opposition leader Boris Nemtsov. He has been in opposition to Vladimir Putin since 2000, backing liberal candidate Grigory Yavlinsky in the 2000 presidential election.


title: Vladimir Kara-Murza

text: Kara-Murza was a candidate for election to the Russian parliament, or State Duma, in the 2003 parliamentary election, running in Moscow's Chertanovsky district. His candidacy was endorsed jointly by the Union of Right Forces and Yabloko. During the campaign, various underhanded methods were used against Kara-Murza. The candidate from the United Russia ruling party Vladimir Gruzdev attempted to have him removed from the ballot; the lighting on Kara-Murza's campaign billboards and the sound during his televised debates were turned off; and unlawful carousel voting was discovered on election day. British journalist Andrew Jack named the Chertanovsky district in south Moscow as a case of electoral manipulation in Russia's 2003 vote in his book "Inside Putin's Russia". According to the official results, Gruzdev received 149,069 votes (53.8%); Kara-Murza, 23,800 votes (8.6%); and Communist Party candidate Sergei Seregin, 18,992 votes (6.9%).


title: Vladimir Kara-Murza

text: In January 2004, he co-founded the Committee 2008, an umbrella opposition group led by Boris Nemtsov and Garry Kasparov. In May 2007, Kara-Murza nominated the veteran human rights activist and writer Vladimir Bukovsky as a democratic opposition candidate for the Russian presidency in the 2008 election. "The opposition needs a candidate for president – strong, uncompromising, decisive, with irreproachable political and, more importantly, moral authority," read the statement written by Kara-Murza on behalf of Bukovsky's campaign committee. "Russia needs its own Vaclav Havel, not a new successor from [the KGB].".


title: Vladimir Kara-Murza

text: From May to December 2007, Kara-Murza chaired Bukovsky's campaign committee, which included, among others, Academician Yuri Ryzhov, writer and satirist Victor Shenderovich, columnist Andrei Piontkovsky, lawyer Yuri Schmidt, human rights activist Alexander Podrabinek, and political analyst Vladimir Pribylovsky. In October 2007, Kara-Murza was one of organisers of the "Rally of Free People" held on Moscow's Triumfalnaya Square in support of Bukovsky's presidential nomination.


title: Vladimir Kara-Murza

text: On 16 December 2007 Bukovsky was duly nominated as a presidential candidate by 823 members of a voters' assembly in Moscow (the law required at least 500 people to support such a nomination). At the same meeting, Kara-Murza was elected as Bukovsky's plenipotentiary representative to Russia's Central Electoral Commission. On 22 December 2007 the Commission refusing to register Bukovsky as a candidate for the presidency, thereby denying Bukovsky access to the ballot.


title: Vladimir Kara-Murza

text: At the founding convention of Solidarnost, Russia's united democratic movement, in December 2008, Kara-Murza was elected to the movement's federal council, placing second out of 77 candidates, behind Nemtsov. He was re-elected to the Solidarnost council in 2010 and 2013.


title: Vladimir Kara-Murza

text: In 2012, he took part in the street protests in Moscow against Putin's rule, the largest pro-democracy demonstrations in Russia since 1991.


title: Vladimir Kara-Murza

text: In June 2012, Kara-Murza was elected to the federal council of the Republican Party of Russia – People's Freedom Party, co-chaired by Boris Nemtsov, Mikhail Kasyanov, and Vladimir Ryzhkov. In October 2012, he was elected to the Coordinating Council of the Russian Opposition, placing 21st out of 169 candidates and receiving 20,845 votes.


title: Vladimir Kara-Murza

text: Soon after, on 1 November 2012, Kara-Murza was hired by the Institute of Modern Russia as the organisation's senior policy advisor. "It is an honor for me to join this distinguished institute and contribute to its mission of keeping the spotlight on the situation in Russia and advocating for democracy, human rights, and the rule of law", said Kara-Murza, "These values should remain at the forefront of international relations." In this capacity he took part in panel discussions about Russia's future at the Heritage Foundation in February 2013 and in October 2013, with Pavel Khodorkovsky (son of the former entrepreneur and philanthropist Mikhail Khodorkovsky) and others, in a similar discussion hosted by the National Endowment for Democracy.


title: Vladimir Kara-Murza

text: Kara-Murza is a coordinator of the Open Russia Foundation, founded by Mikhail Khodorkovsky. The organisation was created with the goal of promoting civil society and democracy in Russia, while revoking Putin's grip on power. Launched in 2014, Open Russia has been instrumental in educating Russian citizens on western democracy, whilst bringing opposition groups and activists in contact with support from the west. Kara-Murza is deputy chairman and heads Open elections project designed to promote free and fair elections in Russia; a task he has noted is exceedingly difficult given the government's ability to silence opposition and manipulate elections. He also frequently addresses international stages to promote further cooperation and discussion among nations.


title: Vladimir Kara-Murza

text: In April 2018, United States Senator John McCain sent Kara-Murza a message revealing that McCain had been diagnosed with brain cancer and requesting that Kara-Murza, who had worked with McCain on issues relating to Russia since 2010, serve as a pallbearer at the senator's eventual funeral. Kara-Murza later said that he was "speechless", "heartbroken", and "close to tears", and that doing so would be "the most heartbreaking honor that anyone could think of". McCain died on 25 August; Kara-Murza joined fourteen others chosen by McCain himself, including the then former Vice President Joe Biden and actor Warren Beatty, as a pallbearer at McCain's funeral at the Washington National Cathedral on 1 September. McCain's choice of Kara-Murza was described by "Politico" as a "final dig" at Putin, of whom McCain was a vocal critic, and at U.S. President Donald Trump, for his apparent closeness to the Russian president.


title: Vladimir Kara-Murza

text: As a journalist and public figure, who was fluent in English and based partly in the US, Kara-Murza played a notable part in the events that led, in 2012, to the passing of the "Magnitsky Act" by the US Congress.


title: Vladimir Kara-Murza

text: In July 2012, Kara-Murza reported that he had been denied access a few days earlier to the Russian Embassy in Washington, D.C. This decision was taken on the orders of the ambassador himself, on the grounds that Kara-Murza was "no longer a journalist". Yet it was not until 1 September that Kara-Murza's dismissal as Washington bureau chief of RTVi was made public. According to several sources he was now on a "blacklist" and could not be employed as a journalist by any Russian media outlets. The reason for this ban was his advocacy of the Sergei Magnitsky Rule of Law Accountability Act, then being considered by the US Congress.


title: Vladimir Kara-Murza

text: The draft law was named after Sergei Magnitsky, a Moscow lawyer who uncovered a massive tax-fraud scheme involving several law-enforcement officials and who died in custody of those same officials in 2009 after being tortured and denied medical care. Its purpose was to prevent the issuing of U.S. visas to persons "responsible for the detention, abuse, or death of Sergei Magnitsky", (and for "extrajudicial killings, torture, or other gross violations of internationally recognized human rights" in Russia) and to freeze access to any U.S.-based assets those persons might hold. The law also extended to cover Russian officials involved in broader acts of corruption and in violations of basic civil liberties. Kara-Murza explained his support for the law by saying that "The prospect of losing access to the West and its financial systems...may well be, for now, the only serious disincentive to corruption and human rights violations by Russian officials."


title: Vladimir Kara-Murza

text: Writing in "The National Interest" Mark Adomanis warned that the Magnitsky law came with a cost. It had "potential downsides," and was worsening "Russia's already precarious human-rights situation", driving "some of the ever-dwindling number of effective opposition journalists" from the country. In particular he cited the firing of Kara-Murza, although the journalist's employers described his dismissal as part of "a long-planned reorganization". Opposition leader Boris Nemtsov, reported Adomanis, "suggested the decision to fire Kara-Murza may have come from an extremely high-ranking official: Alexei Gromov, the deputy head of the presidential administration." An article in July by Peter Baker of "The New York Times" was devoted largely to the arguments of the law's critics. He did quote Kara-Murza's comment that the bill would hit corrupt officials and human-rights violators "where it hurts, closing access to their ill-gotten gains in the West."


title: Vladimir Kara-Murza

text: On 25 July 2012, Kara-Murza testified before the Tom Lantos Human Rights Commission of the U.S. Congress about human-rights abuses in Russia and described the proposed Magnitsky Law as "a pro-Russian bill which provides a much-needed measure of accountability for those who continue to violate the rights and freedoms of Russian citizens." He added: "The Kremlin's reaction to this legislation shows that it hits them precisely where it hurts. I want to take this opportunity to thank Co-Chairmen McGovern and Wolf for their leadership on this issue. I hope the Magnitsky Act is signed into law before the end of this year." In a December 2012 article co-written with Nemtsov, Kara-Murza reiterated his support for the Magnitsky Act which he and Nemtsov called "a pro-Russian law that strikes at the heart of the Kremlin's mafia-like system", adding that "Russian opposition and civil society leaders and cultural figures, as well as a plurality of Russian citizens, are in favour of the Magnitsky law."


title: Vladimir Kara-Murza

text: Kara-Murza and Nemtsov called on Canada to pass a similar piece of legislation, then under consideration by the International Human Rights Subcommittee of the Canadian parliament's House of Commons. Writing for "Maclean's" in December 2012, Michael Petrou reported Kara-Murza's visit to Ottawa to urge the passage of the proposed Canadian version of the Magnitsky law, a private member's bill introduced by Liberal MP Irwin Cotler: while it was the task of Russian opposition leaders, not foreigners, "to bring democratic change to Russia," Kara-Murza said, Western democracies could still help the cause of Russian democracy through legislation. Those in Russia who had abused and tormented Magnitsky "rule in the style of Zimbabwe or Belarus," wrote Petrou, paraphrasing Kara-Murza, "but prefer the West as a safe place to store their money, buy second homes, and send their children to school. And it is in the West where they are most vulnerable."


title: Vladimir Kara-Murza

text: In June 2013, in an interview with France 24 television, Kara-Murza discussed the proposed version of the Magnitsky law then being debated in the European Parliament. He spoke in favour of such laws, and noted that the list of persons covered by the U.S. law was being expanded. He distinguished between those in the European Parliament who were "friends of Russia" and those who were "friends of Putin".


title: Vladimir Kara-Murza

text: In March 2014, noting that the average Russian opposes intervention in Ukraine by the government of Vladimir Putin, Kara-Murza stated that the world "should respond to Putin's aggression" by imposing sanctions against its perpetrators. He called for the list of Russian human-rights abusers who were already banned, under the Sergei Magnitsky Act, from travelling to the United States and keeping assets there to "be dramatically expanded to include senior Kremlin officials responsible for the attack on Ukraine and the crackdown against Russian citizens." He also expressed the hope that "the European Union would soon follow with its own version of the Magnitsky sanctions." "Those who commit acts of aggression and abuse the rights of their own citizens should not be entitled to the privileges and comfort of the democratic West," he said.


title: Vladimir Kara-Murza

text: On 27 February 2015, opposition leader Boris Nemtsov was assassinated by four shots from behind while he was sitting on a bridge near Red Square in Moscow. According to Bill Browder, Kara-Murza is a protégé of Nemtsov.


title: Vladimir Kara-Murza

text: In late April 2015, Kara-Murza and Mikhail Kasyanov presented a list of eight names to members of the House of Representatives and the Senate of the US Congress. These were the TV presenters and other state-employed journalists and commentators who, Kara-Murza and Kasyanov alleged, had created an atmosphere of "hatred, intolerance and violence" around the figure of Nemtsov in the months leading up to his murder one hundred yards from the Kremlin. Specifically, the named individuals had stated on nationwide television that Nemtsov was a traitor, an enemy of Russia, part of a "fifth column" within the country, and that he would have welcomed the invading German forces outside Moscow in 1941.


title: Vladimir Kara-Murza

text: Kara-Murza explained the appeal to U.S. legislators by saying that Russia's law-enforcement agencies, unfortunately, had declined to investigate these recorded and documented statements although incitement to harm an individual was also a crime according to the Criminal Code of the Russian Federation. These eight names, Kara-Murza hoped, would now be added to those already on the Magnitsky List. The eight names were listed in the "Kommersant" daily newspaper.


title: Vladimir Kara-Murza

text: On 18 May 2015, the daily newspaper "Komsomolskaya Pravda" reported that Yevgeny Alexeyevich Fyodorov, a State Duma deputy for United Russia, had requested the Investigative Committee of the Russian Federation to assess whether Kasyanov and Kara-Murza had not committed an act of treason, under Article 275 of the RF Criminal Code, by submitting the above list of eight names to members of the US Congress. When approached by the newspaper the Investigative Committee would not pass comment on deputy Fyodorov's statement.


title: Vladimir Kara-Murza

text: On 26 May 2015, Kara-Murza was suddenly taken ill in Moscow during a meeting. He had eaten lunch at a restaurant and then had a two-hour meeting, during which he consumed nothing and felt normal, before becoming ill over a ten to fifteen minute period, leading to vomiting. At first he was thought to be having heart difficulties, but treatment at a specialised cardiac clinic did nothing to arrest the symptoms. Kara-Murza was then taken to hospital in Moscow. Initial symptoms indicated that he could have been poisoned, according to doctors, and he was later diagnosed with kidney failure.


title: Vladimir Kara-Murza

text: Coming after the murder of his colleague Boris Nemtsov on 27 February 2015, and mindful of other cases of poisoning, both in Russia (journalist and Duma deputy Yuri Shchekochikhin in 2003, the attempted murder of Anna Politkovskaya in 2004) and abroad (Alexander Litvinenko in October 2006) there was great concern on the part of friends and family. His wife Yevgenia urged that he be evacuated from Russia for examination and treatment abroad. On 2 June, it was announced by a spokesman for the Republican Party of Russia – People's Freedom Party that Kara-Murza had emerged from his coma and recognised his wife, who was now by his bedside. The cause of his sudden illness remained a mystery, but in an interview with the BBC his father commented, "if someone did want to frighten us, then they succeeded." There has never been any conclusive evidence that Kara-Murza has ever been intentionally poisoned.


title: Vladimir Kara-Murza

text: After his release from the hospital, Kara-Murza stated that it was difficult to "believe this was an accident", suspecting it was an intentional poisoning, but noted there was no way to be certain. On 15 August 2015, Mikhail Khodorkovsky commented with delight that Kara-Murza had returned to work co-ordinating the Open Elections project. Kara-Murza is working to provide free and fair elections for the Duma.


title: Vladimir Kara-Murza

text: On 2 February 2017, Kara-Murza was again hospitalised after the onset of the same symptoms as his prior illness. He was put in a medically-induced coma and was on life support. He was treated at the same hospital by the same medical team who had already saved his life in 2015. According to his lawyer Vadim Prokhorov, Kara-Murza was diagnosed by the hospital with 'toxic influence of an unknown substance'. He was released on 19 February and went abroad for rehabilitation. His lawyer sent the Russian Investigative Committee a request to open a criminal case into the alleged poisoning. A similar request after the 2015 incident had been turned down without an explanation.


title: Vladimir Kara-Murza

text: His blood samples were provided to a number of laboratories including one affiliated to the FBI. But for unclear reasons, the FBI subsequently have not revealed details of their investigations into the substance that triggered Kara-Murza's illness, with one US Senator suggesting that it might be "classified". Two other labs—in France and Israel—have also conducted tests, but they were inconclusive.


title: Vladimir Kara-Murza

text: In February 2021, a Bellingcat joint investigation with "The Insider" and "Der Spiegel" said that Kara-Murza had been followed by the same FSB unit that allegedly poisoned Alexei Navalny before he fell ill in 2015 and 2017.


title: Vladimir Kara-Murza

text: His longtime lawyer, Vadim Prokhorov, said Kara-Murza had been arrested on Monday 11 April 2022 on charges of disobeying police orders, and faced up to 15 days in jail or a small fine. It was not immediately clear if Kara-Murza’s arrest was linked to his opposition to Russia’s actions in Ukraine. On 22 April 2022, Kara-Murza was charged by a Russian court for spreading of “false” information about the Russian military. The reason for the criminal case against Kara-Murza was his March 15 speech to the Arizona House of Representatives, in which he denounced the Russian invasion of Ukraine.


title: Vladimir Kara-Murza

text: In July, new charges of cooperating with an "undesirable" foreign NGO were introduced, in which he faced up to six years in prison. In October, Prokhorov said that Kara-Murza faced new charges of treason, in which he faced up to 20 years in prison.


title: Interferon gamma

text: Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock as a product of human leukocytes stimulated with phytohemagglutinin, and by others as a product of antigen-stimulated lymphocytes. It was also shown to be produced in human lymphocytes. or tuberculin-sensitized mouse peritoneal lymphocytes challenged with Mantoux test (PPD); the resulting supernatants were shown to inhibit growth of vesicular stomatitis virus. Those reports also contained the basic observation underlying the now widely employed IFN-γ release assay used to test for tuberculosis. In humans, the IFN-γ protein is encoded by the "IFNG" gene.


title: Interferon gamma

text: IFN-γ, or type II interferon, is a cytokine that is critical for innate and adaptive immunity against viral, some bacterial and protozoan infections. IFN-γ is an important activator of macrophages and inducer of major histocompatibility complex class II molecule expression. Aberrant IFN-γ expression is associated with a number of autoinflammatory and autoimmune diseases. The importance of IFN-γ in the immune system stems in part from its ability to inhibit viral replication directly, and most importantly from its immunostimulatory and immunomodulatory effects. IFN-γ is produced predominantly by natural killer cells (NK) and natural killer T cells (NKT) as part of the innate immune response, and by CD4 Th1 and CD8 cytotoxic T lymphocyte (CTL) effector T cells once antigen-specific immunity develops as part of the adaptive immune response. IFN-γ is also produced by non-cytotoxic innate lymphoid cells (ILC), a family of immune cells first discovered in the early 2010s.


title: Interferon gamma

text: The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region. This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6.


title: Interferon gamma

text: The biologically active dimer is formed by anti-parallel inter-locking of the two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue.


title: Interferon gamma

text: Cellular responses to IFN-γ are activated through its interaction with a heterodimeric receptor consisting of Interferon gamma receptor 1 (IFNGR1) and Interferon gamma receptor 2 (IFNGR2). IFN-γ binding to the receptor activates the JAK-STAT pathway. Activation of the JAK-STAT pathway induces upregulation of interferon-stimulated genes (ISGs), including MHC II. IFN-γ also binds to the glycosaminoglycan heparan sulfate (HS) at the cell surface. However, in contrast to many other heparan sulfate binding proteins, where binding promotes biological activity, the binding of IFN-γ to HS inhibits its biological activity.


title: Interferon gamma

text: The structural models shown in figures 1-3 for IFN-γ are all shortened at their C-termini by 17 amino acids. Full length IFN-γ is 143 amino acids long, the models are 126 amino acids long. Affinity for heparan sulfate resides solely within the deleted sequence of 17 amino acids. Within this sequence of 17 amino acids lie two clusters of basic amino acids termed D1 and D2, respectively. Heparan sulfate interacts with both of these clusters. In the absence of heparan sulfate the presence of the D1 sequence increases the rate at which IFN-γ-receptor complexes form. Interactions between the D1 cluster of amino acids and the receptor may be the first step in complex formation. By binding to D1 HS may compete with the receptor and prevent active receptor complexes from forming.


title: Interferon gamma

text: The biological significance of heparan sulfates interaction with IFN-γ is unclear; however, binding of the D1 cluster to HS may protect it from proteolytic cleavage.


title: Interferon gamma

text: IFN-γ is secreted by T helper cells (specifically, T1 cells), cytotoxic T cells (T cells), macrophages, mucosal epithelial cells and NK cells. IFN-γ is both an important autocrine signal for professional APCs in early innate immune response, and an important paracrine signal in adaptive immune response. The expression of IFN-γ is induced by the cytokines IL-12, IL-15, IL-18, and type I IFN. IFN-γ is the only Type II interferon and it is serologically distinct from Type I interferons; it is acid-labile, while the type I variants are acid-stable.


title: Interferon gamma

text: IFN-γ has antiviral, immunoregulatory, and anti-tumor properties. It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Among the effects are:


title: Interferon gamma

text: IFN-γ is the primary cytokine that defines T1 cells: T1 cells secrete IFN-γ, which in turn causes more undifferentiated CD4 cells (Th0 cells) to differentiate into T1 cells


title: Interferon gamma

text: , representing a positive feedback loop—while suppressing T2 cell differentiation. (Equivalent defining cytokines for other cells include IL-4 for T2 cells and IL-17 for Th17 cells.)


title: Interferon gamma

text: NK cells and CD8+ cytotoxic T cells also produce IFN-γ. IFN-γ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NF-κB.


title: Interferon gamma

text: A granuloma is the body's way of dealing with a substance it cannot remove or sterilize. Infectious causes of granulomas (infections are typically the most common cause of granulomas) include tuberculosis, leprosy, histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis, and toxoplasmosis. Examples of non-infectious granulomatous diseases are sarcoidosis, Crohn's disease, berylliosis, giant-cell arteritis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, pulmonary rheumatoid nodules, and aspiration of food and other particulate material into the lung. The infectious pathophysiology of granulomas is discussed primarily here.


title: Interferon gamma

text: The key association between IFN-γ and granulomas is that IFN-γ activates macrophages so that they become more powerful in killing intracellular organisms. Activation of macrophages by IFN-γ from T1 helper cells in mycobacterial infections allows the macrophages to overcome the inhibition of phagolysosome maturation caused by mycobacteria (to stay alive inside macrophages). The first steps in IFN-γ-induced granuloma formation are activation of T1 helper cells by macrophages releasing IL-1 and IL-12 in the presence of intracellular pathogens, and presentation of antigens from those pathogens. Next the T1 helper cells aggregate around the macrophages and release IFN-γ, which activates the macrophages. Further activation of macrophages causes a cycle of further killing of intracellular bacteria, and further presentation of antigens to T1 helper cells with further release of IFN-γ. Finally, macrophages surround the T1 helper cells and become fibroblast-like cells walling off the infection.


title: Interferon gamma

text: Uterine Natural Killer cells (NK) secrete high levels of chemoattractants, such as IFN-γ in mice. IFN-γ dilates and thins the walls of maternal spiral arteries to enhance blood flow to the implantation site. This remodeling aids in the development of the placenta as it invades the uterus in its quest for nutrients. IFN-γ knockout mice fail to initiate normal pregnancy-induced modification of decidual arteries. These models display abnormally low amounts of cells or necrosis of decidua.


title: Interferon gamma

text: In humans, elevated levels of IFN-γ have been associated with increased risk of miscarriage. Correlation studies have observed high IFN-γ levels in women with a history of spontaneous miscarriage, when compared to women with no history of spontaneous miscarriage. Additionally, low-IFN-γ levels are associated with women who successfully carry to term. It is possible that IFN-γ is cytotoxic to trophoblasts, which leads to miscarriage. However, causal research on the relationship between IFN-γ and miscarriage has not been performed due to ethical constraints.


title: Interferon gamma

text: Recombinant human IFN-γ, as an expensive biopharmaceutical, has been expressed in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. Human IFN-γ is commonly expressed in "Escherichia coli", marketed as ACTIMMUNE®, however, the resulting product of the prokaryotic expression system is not glycosylated with a short half-life in the bloodstream after injection; the purification process from bacterial expression system is also very costly. Other expression systems like "Pichia pastoris" did not show satisfactory results in terms of yields.


title: Interferon gamma

text: Interferon-γ 1b is approved by the U.S. Food and Drug Administration to treat chronic granulomatous disease (CGD) and osteopetrosis. The mechanism by which IFN-γ benefits CGD is via enhancing the efficacy of neutrophils against catalase-positive bacteria by correcting patients' oxidative metabolism.


title: Interferon gamma

text: It was not approved to treat idiopathic pulmonary fibrosis (IPF). In 2002, the manufacturer InterMune issued a press release saying that phase III data demonstrated survival benefit in IPF and reduced mortality by 70% in patients with mild to moderate disease. The U.S. Department of Justice charged that the release contained false and misleading statements. InterMune's chief executive, Scott Harkonen, was accused of manipulating the trial data, was convicted in 2009 of wire fraud, and was sentenced to fines and community service. Harkonen appealed his conviction to the U.S. Court of Appeals for the Ninth Circuit, and lost. Harkonen was granted a full pardon on January 20, 2021.


title: Interferon gamma

text: Preliminary research on the role of IFN-γ in treating Friedreich's ataxia (FA) conducted by Children’s Hospital of Philadelphia has found no beneficial effects in short-term (< 6-months) treatment. However, researchers in Turkey have discovered significant improvements in patients' gait and stance after 6 months of treatment.


title: Interferon gamma

text: Although not officially approved, Interferon-γ has also been shown to be effective in treating patients with moderate to severe atopic dermatitis. Specifically, recombinant IFN-γ therapy has shown promise in patients with lowered IFN-γ expression, such as those with predisposition to herpes simplex virus, and pediatric patients.


title: Interferon gamma

text: IFN-γ increases an anti-proliferative state in cancer cells, while upregulating MHC I and MHC II expression, which increases immunorecognition and removal of pathogenic cells. IFN-γ also reduces metastasis in tumors by upregulating fibronectin, which negatively impacts tumor architecture.


title: Interferon gamma

text: IFN-γ is not approved yet for the treatment in any cancer immunotherapy. However, improved survival was observed when IFN-γ was administrated to patients with bladder carcinoma and melanoma cancers. The most promising result was achieved in patients with stage 2 and 3 of ovarian carcinoma. On the contrary, it was stressed: "Interferon-γ secreted by CD8-positive lymphocytes upregulates PD-L1 on ovarian cancer cells and promotes tumour growth." The "in vitro" study of IFN-γ in cancer cells is more extensive and results indicate anti-proliferative activity of IFN-γ leading to the growth inhibition or cell death, generally induced by apoptosis but sometimes by autophagy. In addition, it has been reported that mammalian glycosylation of recombinant human IFN-γ, expressed in HEK293, improves its therapeutic efficacy compared to the unglycosylated form that is expressed in "E. coli".


title: Interferon gamma

text: Interferon-γ has been shown to interact with Interferon gamma receptor 1 and Interferon gamma receptor 2.


title: Interferon gamma

text: Interferon-γ has been shown to be a crucial player in the immune response against some intracellular pathogens, including that of Chagas disease. It has also been identified as having a role in seborrheic dermatitis.