Op Cit Research Articles

Reflections: Educate with knowledge in an edifying key

Reflections: Educate with knowledge in an edifying key

Approximately multiplicative maps between algebras of bounded operators on Banach spaces

We show that for any separable reflexive Banach space X X and a large class of Banach spaces E E , including those with a subsymmetric shrinking basis but also all spaces L p [ 0 , 1 ] L_p[0,1] for 1 ≤ p ≤ ∞ 1\le p \le \infty , every bounded linear map B ( E ) → B ( X ) \mathcal {B}(E)\to \mathcal {B}(X) which is approximately multiplicative is necessarily close in the operator norm to some bounded homomorphism B ( E ) → B ( X ) \mathcal {B}(E)\to \mathcal {B}(X) . That is, the pair ( B ( E ) , B ( X ) ) (\mathcal {B}(E),\mathcal {B}(X)) has the AMNM property in the sense of Johnson [J. London Math. Soc. (2) 37 (1988), pp. 294–316]. Previously this was only known for E = X = ℓ p E=X=\ell _p with 1 > p > ∞ 1>p>\infty ; even for those cases, we improve on the previous methods and obtain better constants in various estimates. A crucial role in our approach is played by a new result, motivated by cohomological techniques, which establishes AMNM properties relative to an amenable subalgebra; this generalizes a theorem of Johnson (op cit.).

Translatology: What Hobbles It

Noting that man hasn’t as yet awakened fully rationally to the life-giving life-enhancing power and life-refreshing life-sourcing civilization-deepening beauty of literary translation, the Note argues that the possible anodynity of (Literary) Translation Sciences as they obtain today cry out for a good deal of rationally illuminating rigorisation. Part of the anodynity is linguistic (and cultural) naiveté, as we argue. See Giridhar 2005 for a rational elucidation. Lexicalisations like the Sanskrit word dharma for example have been subjected to unacceptably naïve, irrational and supremacist, and hence glaringly unscientific, treatment. This has been demonstrated (See Giridhar op cit). We will talk about it here as well. Part of the problem is the waffly kind of demagoguery that sustains itself over the years. For example, people talk(ed) of eco-translation. Has any piece been translated with eco-translation in mind? If not, what is its status? It, as seems to be the case, exists in the air as cerebral gymnastics? Is there a translation precept which has no conceivable relation to translation praxis? Following Ramayana’s several regional avatars, there was some piquant and fashionably exultant buzz about originals undergoing several forms in response to the narrativisation requirements of target cultures. I know of no modern literary piece which has had such avatars because apparently, the translator doesn’t know what to do! Does it mean these different avatars, however nebulously defined, are theoretically optional? Adaptation, I rationally assume, is technically different from translation. Essentially, there is no ‘adaptation’, for example, for discursive or scientific discourse.

Abstract A61: Tumor metabolic remodeling can modulate anticancer drug response: CPI-613 attack on tumor cell mitochondrial metabolism is mediated by metabolite availability

Abstract We will describe recent progress in understanding the role of cancer metabolic remodeling in determining the response of tumors and tumor cells to a novel, first-in-class clinical agent class selectively targeting cancer cell mitochondrial metabolism. The reconfiguration of mitochondrial metabolism in cancer in general, and the tricarboxylic acid (TCA) cycle in particular, presents a rich source of potential therapeutic targets. Pyruvate dehydrogenase (PDH) and alpha ketoglutarate dehydrogenase (KGDH) are two gatekeeper enzymes regulating carbon flux into the mitochondrial TCA cycle. A key component of the altered regulatory processes in cancer is lipoic acid (lipoate), which not only functions as a cofactor for both PDH and KGDH, but also as source of regulatory information. Moreover, the lipoate-sensitive regulatory components of PDH and KGDH are substantially reconfigured in tumor cells, providing cancer-specific targets that can be successfully attacked with properly designed lipoate analogs. We developed and characterized CPI-613, a lipoic acid analog, which selectively targets mitochondrial metabolism in tumor cells by mobilizing lipoate-sensitive, cancer-specific regulation of PDH and KGDH, shutting down the two enzymes and thereby choking carbon flow through the TCA cycle. This attack on mitochondrial metabolism redundantly activates multiple cell death pathways (Zachar, et al., 2011, J Mol Med 89, 1137; Stuart, et al., 2014, Cancer&Metab 2, 4). In vitro, CPI-613 is uniformly effective in killing tumor cell lines (more than 50 tumor lines tested to date). Moreover, these drugs have produced compelling clinical responses (including complete remissions) in some, but not all patients with advanced, refractory, heavily pre-treated cancers in initial Phase I/II clinical trials (Pardee et al., 2014, Clin Cancer Res 20:5255). In an effort to explore the mechanisms of CPI-613 activity and characterize the reasons for differential patient responses, we have shown that the kinetics of the cancer cell death response to CPI-613 is profoundly affected by the carbon sources available to the cell (Zachar, et al., 2011, J Mol Med 89, 1137). For example, in media where pyruvate and glutamine (capable of producing net ATP synthesis only in the mitochondrial compartment) are the major carbon sources, death is rapid, completed within 4 hours (op cit). In contrast, when glucose is substituted for pyruvate, the cell death programs take up to 48 hours to complete. We have analyzed the mechanistic basis of this and related observations, including steady state and flux metabolomics, pharmacological inhibitors of non-TCA metabolic pathways, and manipulation of media composition to systematically characterize these dramatic effects of nutrient availability on cancer cell drug response. Our results demonstrate that CPI-613 induced inactivation of tumor cell KGDH is modulated by the potency of mitochondrial redox detoxification (Stuart, et al., 2014, Cancer&Metab 2, 4). Given that various metabolic pathways (for example, glycolysis) can ultimately contribute to mitochondrial ROS detoxification potential, it appears that substrate availability powerfully influences the cellular response to CPI-613. These insights open a number of fundamentally new approaches to increasing the fraction of patients who respond strongly to CPI-613 in the clinic. We will also report pre-clinical studies targeted at allowing planned future clinical trials to exploit these new insights. Citation Format: Shawn D. Stuart, Moises Guardado, Michael Dahan, Paul M. Bingham, Zuzana Zachar. Tumor metabolic remodeling can modulate anticancer drug response: CPI-613 attack on tumor cell mitochondrial metabolism is mediated by metabolite availability. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr A61.

Rome, Open for British Production: The lost world of ‘Britalian’ films, 1946-1954

It may be that the war has forced some of us British producers to be too insular in our outlook. We have failed to realise that Europe can provide an ideal location centre, not for completing parts...

Dasatinib combined with gemcitabine (Gem) in patients (pts) with locally advanced pancreatic adenocarcinoma (PaCa): Design of CA180-375, a placebo-controlled, randomized, double-blind phase II trial.

TPS4134 Background: Dasatinib, a potent oral BCR-ABL and SRC family kinase (SFK) inhibitor, is approved for first- and second-line therapy of Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (CML) in pts with newly diagnosed CML or CML resistant/intolerant to prior therapy. SRC expression and activity is upregulated in PaCa and correlates with reduced survival in resected high-grade PaCa (Morton, Gastroenterology 2010) and resistance to Gem, a PaCa standard of care (Duxbury, J Am Coll Surg 2004). In preclinical PaCa studies, inhibition of SFKs with dasatinib reduces tumor cell proliferation, migration, and invasion; increases apoptosis; sensitizes cells to Gem; and inhibits development of metastases in vivo either alone or in combination with Gem (Duxbury, Clin Cancer Res 2004; Duxbury, J Am Coll Surg 2004; Nagaraj, Mol Cancer Ther 2010; Morton, op cit). Phase I clinical studies of dasatinib and Gem therapy in PaCa have demonstrated feasibility and suggested efficacy of the combination (Uronis, ASCO 2009, abstract e15506). Methods: This double-blind phase II study tests whether addition of dasatinib to Gem is tolerable and improves efficacy in pts with histologically/cytologically confirmed unresectable locally advanced nonmetastatic PaCa. Eligible pts, aged ≥18 years with Eastern Cooperative Oncology Group performance status ≤1 and adequate organ function, are randomized 1:1 to Gem 1000 mg/m2 IV once weekly (Weeks 1–3 of a 4-week cycle) plus either dasatinib 100 mg once daily or matched placebo. Pts are treated until progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary endpoint is OS, and secondary endpoints are progression-free survival and safety. Exploratory endpoints include freedom from distant metastases, measures of pain and fatigue, overall response rate, and carbohydrate antigen 19-9. Final study analysis will be conducted after 135 deaths; all pts will be followed for survival. To date, 23/200 pts have enrolled; estimated primary completion date is March 2013. ClinicalTrials.gov identifier: NCT01395017.

Russia Returns to the Middle East: 2005-2011

The Maghreb Review, Vol. 36, 2, 2011 © The Maghreb Review 2011 This publication is printed on longlife paper RUSSIA RETURNS TO THE MIDDLE EAST: 2005-2011 BY ROBERT O. FREEDMAN∗ INTRODUCTION During his first term in office [2000-2004] Russian President Vladimir Putin took a basically defensive position in the Middle East, much as his predecessor Boris Yeltsin had done1 . With an economy still recovering from the devastating collapse of 1998 [although oil prices, critical to the Russian economy, had begun to rise], with an ugly insurgency still raging in Chechnya and the North Caucasus, and with his domestic opposition still not yet fully suppressed, Putin adopted a cautious policy in the region and elsewhere in the world as well. To be sure, in the case of Iran, Putin did abrogate the Gore-Chernomyrdin agreement of 1995, under which Russia promised to end all arms sales to Iran by the end of 1999. Nonetheless, he also took an increasingly critical position toward Iran’s nuclear programme, once Iran’s secret facilities for the enrichment of uranium were discovered, even threatening, in June 2004, to hold up the construction of the Bushehr nuclear reactor which Russia was building in Iran2 . In the case of the US invasion of Iraq, Putin took a strongly critical position, but one that was also shared by America’s NATO allies, France and Germany3 . In the case of the Arab-Israeli conflict, Putin continued the proArab tilt begun under Yeltsin when Yevgeny Primakov had become Russia’s Foreign Minister in 1996. 4 In part, Putin’s position seems to have been related to his efforts to curry favour with the Arabs so as to try to get them to limit their aid to the rebellion in Chechnya, which by the late 1990’s had taken on a clear Islamic nature. Indeed, one of Putin’s policy innovations during his first term as Russia’s President was to seek the support of Organization of the Islamic Conference [OIC] for his policies in Chechnya, and in 2003 he applied for observer status in the organization, basing his claim on the fact that there were 20 million Moslems living in the Russian Federation.5 Another policy ∗ John Hopkins University. I am indebted to my research assistant at Johns Hopkins University, Mr. Alex Shtarkman, for his research input in this article. 1 For an overview of Russian policy toward the Middle East under Yeltsin, see Robert O. Freedman, Russian Policy Toward The Middle East Since The Collapse Of The Soviet Union: The Yeltsin Legacy And The Challenge For Putin [Seattle: Henry Jackson School of International Studies, University of Washington,1991] 2 For a detailed analysis of Russian-Iranian relations from 1991-2006, see Robert O. Freedman, Russia, Iran And The Nuclear Question: The Putin Record [Carlisle, Pennsylvania: the Strategic Studies Institute of the US Army War College,2006] 3 Putin’s strategy during the war is discussed in, Robert O. Freedman, “Can Russia be a Partner for the United States in the Middle East?”, in Nato-Russian Relations [ed. Aurel Braun] [New York: Routledge, 2008] 4 Freedman, Russian Policy Toward The Middle East, op. cit 5 Freedman, Can Russia be a Partner, op cit 128 ROBERT O. FREEDMAN continuity from the latter part of the Yeltsin era was the attempt to improve Russian-Turkish relations. Indeed, in 2000 Putin called for the transformation of relations with Turkey from competition to cooperation, and trade between Russia and Turkey was to rise rapidly, based in large part on Russian supplies of natural gas to Turkey and the construction of the “Blue Stream” natural gas pipeline across the Black Sea under an agreement signed by the two countries in 1997. By June 2004, with his domestic opponents under control, overwhelmingly reelected to a second term as Russia’s President, with oil prices rising rapidly and the Russian economy showing major signs of improvement, Putin was ready to move ahead with his three major objectives for Russia; [1] restoring Russia’s status as a great power, thereby ending American dominance of the post-Cold War world; [2] developing the Russian economy, particularly in the high-tech area, so Russia would not be so dependent...

The 1931 Australian Federal Election—Radio Makes History

Click to increase image sizeClick to decrease image size Acknowledgement I would like to thank the Australian Prime Minister's Centre in Canberra for the Fellowship that enabled the research in this paper to take place Notes 1 Bridget Griffen-Foley, Changing Stations—the story of Australian commercial radio (Sydney, UNSW Press, 2009), 354. 2 Murray Goot, ‘Radio Lang’ Heather Radi and Peter Spearritt, Lang (Hlae & Iremonger, Neutral Bay, 1977), 121. 3 National Archives of Australia, Royal Commission on The Wireless (1927), A432, 1232. 4 Ibid., 4076. 5 The Argus, 25 November 1931. 6 Ibid., 6. 7 Alan Thomas, Broadcast and Be Damned (Melbourne, MUP, 1980), 11–12. 8 The Canberra Times, 20 November 1929. 9 Ian Ward, The early use of radio for political communication in Australia and Canada: John Henry Austral, Mr Sage and the Man from Mars, Australian Journal of Politics and History, 45(3) (1999), 311–329. 10 John Robertson, James Scullin: a political biography (UWA Press, Nedlands, 1974), 209. 11 National Library of Australia, Dumas Collection, MS4849, 9 April 1931. 12 Griffen-Foley, op. cit., 14. 13 Anne Henderson, Enid Lyons—leading lady to a nation (Pluto Press, North Melbourne, 2008), 172. 14 David Bird, J. A. Lyons—the ‘tame Tasmanian’ (ASP, North Melbourne, 2008), 21. 15 Sir Henry Gullett, quoted in Brendan Lyons, They Loved Him To Death (self-published, Kings Meadows, 2008), 125–126. 16 Northern Territory Times, 10 April 1931. 17 Canberra Times, 30 June 1931, 2. 18 Adelaide Advertiser, 22 July 1931. 19 National Archives of Australia, Lyons's papers, CP103/19. 20 Ibid. 21 Commonwealth Parliamentary Debates, 28–29 July 1931, 4494. 22 Ibid, 4495. 23 Lyons's papers, op cit. 24 Ibid. 25 CPD, 28–29 July 1931, 4497. 26 Robertson, op. cit., 371. 27 Brisbane Courier Mail, 26 November 1931. 28 Clem Lloyd, The rise and fall of the United Australia Party, in: John Nethercote Liberalism and the Australian Federation (Federation Press, Annandale, 2001), 134–162. 29 Ibid. 30 Stephen Glover, The Guardian, 4 April 2005. 31 John Antcliffe (1984) Politics of the airwaves, History Today, 34(3) (1984), 6. 32 Kevin Morgan, Ramsay MacDonald (Haus Publishing, London, 2006), 92. 33 Lance Price, Where Power Lies: Prime Ministers vs the media (Simon and Schuster, London, 2010), 82. 34 R. Bassett, 1931—A Political Crisis (MacMillan, London, 1958), 445. 35 Ibid., 321. 36 Ibid. 37 Ibid., 327. 38 Sydney Morning Herald, 22 January 1931. 39 The Listener In, 5 December 1931. 40 Ibid. 41 The Argus, 28 November 1931. 42 Sydney Morning Herald, 28 November 1931. 43 Ward, op. cit., 321. 44 Listener In, ibid. 45 Griffen-Foley, op. cit., 357. 46 Listener In, 18 December 1931. 47 Sydney Morning Herald, 22 January 1931. 48 D. R. Hall, Development of political parties, in W. G. K. Duncan, Trends in Australian Politics (Angus & Robertson, Sydney, 1935), 29. 49 Ibid. 50 Wireless Weekly, 24 October 1930. 51 Antcliffe, op. cit., 4. 52 Ward, op. cit., 325. 53 Ibid., 324. 54 Wireless Weekly, op. cit. 55 Hall, op. cit., 32.

Cholesterol Deficiency, Statins and Rhabdomyolysis

Cholesterol's (CH) function cannot be to stiffen membranes because: 1) We synthesize CH but cannot burn it for energy; 2) Mankind has over 100 genes devoted to CH management, regulation, trucking, biosynthesis, degradation, etc. 3) Unlike CH plant sterols have branches on their sidechains. 4) Most cultured animal cells die without CH. 5) We have >2 ABC intestinal transporters that selectively block phytosterol uptake. 6) The lipid mole fraction of CH rises and falls with the [Na+] that faces the membrane. Literature evidence is here gathered that shows cells in vivo leak Na+ due to the ΔΨ and the blood [Na+] which is 0.1M. Although the Na+ leakage is slow (10−12 cm/sec) compared to H+ leakage (10−5 cm/sec), the high [Na+] makes them equivalent. Furthermore the presence of 1/3 mole% CH, as typically found in membranes facing blood, reduces the Na+ leakage to 1/3 that found in bilayers lacking CH. FDA data suggest excess statins taken by ∼200 patients in the last 8 years resulted in lethal rhabdomyolysis (RH). If cholesterol's function is to limit Na+ leakage (Prog. Lipid Res. 40 (2001) 299), then 3 times as much ATP is needed to compensate for leaked Na+. Muscle cells, lacking a pentose shunt cannot make much NADPH, which is essential for CH synthesis. Such a CH deficiency in muscle would provoke Na+ leakage into cells that may burst because of osmotic swelling. A common feature of RH in autopsies is that salt is found in the muscle cells. Due to the branches on their side chains, plant sterols appear to be designed to inhibit H+ leakage (op cit.). They are only found where the plasma membrane has a H+ gradient. CH is only found in cells where the plasma membranes facing Na+.

Science and the cultural imaginary: the case of Kazuo Ishiguro's Never Let Me Go

When Kazuo Ishiguro's sixth novel, Never Let Me Go, was published in 2005, it was extensively reviewed as one would expect of the work by an author whose previous oeuvre has been widely acclaimed a...

Structural borrowing: The case of Kenyan Sign Language (KSL) and Kiswahili contact signing

Kenyan Sign Language (KSL) is a visual gestural language used by members of the deaf community in Kenya. Kiswahili on the other hand is a Bantu language that is used as the national language of Kenya. The two are world's apart, one being a spoken language and the other a signed language and thus their “… basic structural units are of necessity fundamentally very different…” (Valli and Lucas: 1996). However, preliminary investigations have revealed that sometimes Kenyan signers use KSL signs while mouthing in Kiswahili. However, this does not necessarily put a case for the existence of a Kiswahili sign language since KSL is a natural language with its own autonomous grammar distinct from that of any spoken language. In this paper, we shall argue that the Kiswahili mouthed KSL signs are an outcome of contact between KSL – Kiswahili bilinguals and their hearing Kiswahili bilingual counterparts. Following Valli and Lucas (1996). We will further argue that there are no contact signs in a situation where a sign language is in contact with a spoken language this being due to the fact that spoken languages do not have signed forms and thus no new signs are formed due to this contact. The signing in a KSL – Kiswahili contact results into a phenomenon called contact signing. The paper further argues that as a result of interaction between KSL and Kiswahili, KSL users sometimes code switch/code mix in a contact situation that involves hearing Kiswahili users and surprisingly in some deaf – deaf contact situations. This interaction has led to what Davis (in Valli and Lucas op cit) call “unique phenomenon” that manifests itself in – mouthing, finger spelling, code switching/mixing and contact signing. Journal of Language, Technology & Entrepreneurship in Africa Vol. 1 (2) 2009: pp. 160-174

Why NATO Should Return Home The Case for a Twenty-First Century Alliance

Click to increase image sizeClick to decrease image size Notes 1. Richard Haas, ‘The Age of Non-polarity’, Foreign Affairs (Vol. 87, No. 3, May/June 2008), p. 45. 2. Fareed Zakaria, ‘The Future of American Power’, Foreign Affairs (Vol. 87, No. 3, May/June 2008), p. 40. 3. John McCain, ‘An Enduring Peace Built on Freedom’, Foreign Affairs (Vol. 86, No. 6, November/December 2007), pp. 19-35. 4. Ivo Daalder and James Goldgeier, ‘Global NATO’, Foreign Affairs (Vol. 85, No. 5, September/October 2006), pp 105-112. 5. Mikkel Rasmussen, The Risk Society At War: Terror, Technology and Strategy in the Twenty-First Century (Cambridge: Cambridge University Press, 2006). 6. P J O'Rourke, Peace Kills: America's Fun New Imperialism (London: Picador, 2005), p. 26. 7. Cited by John Kampfner, Blair's Wars (London: Free Press, 2003) p 3. 8. The Economist, 2 June 2007. 9. Alex De Waal, ‘Against Gunboat Philanthropy’, Prospect, June 2008, p 19. 10. Niall Ferguson, War of the World: History's Age of Hatred (London: Allen Lane, 2006). 11. Daniel Bell, The End of Ideology (Cambridge: Harvard University Press, 2000) p xix. 12. Mark Leonard, What Does China Think? (London: Fourth Estate, 2008). 13. Henry Porter, ‘The New World Order That Threatens Uncle Sam’, The Observer, 23 December 2007. 14. Dimitri Trenin, ‘Russia Leaves the West’, Foreign Affairs (Vol. 84, No. 4, July/August 2006), p 87. 15. M K Bhadrakumar, ‘The Great Game on a Razor's Edge – The Stakes Go Up In Central Asia’, Asia Times Online, 23 December 2006, < http://www.atimes.com/atimes/central_asia/hl23ag01.html> accessed 5 May 2007. 16. Ramakant Dwivedi, ‘China's Central Asia Policy in Recent Times’, China and Eurasia Forum Quarterly (Vol. 4, No. 4, 2006), pp.139-152. 17. Bates Gill, ‘China's Evolving Regional Security Strategy’ in David Shambaugh, Powershift –China and Asia's New Dynamics (Berkeley: University of California Press, 2005). 18. Andrzej Zwaniecki, ‘IMF Governance Reform Aims at Fairer Multilateral Organization’, The Washington File, 12 September 2006, < http://www.america.gov/st/washfile-english/2006/September/20060912132016SAikceinawz0.2876856.html >. 19. Daniel Drezner, ‘The New World Order’, Foreign Affairs (Vol. 86, No. 2, March/April 2007), p 43. 20. Hugh Williamson, ‘Great Powers Try To Keep It Casual’, The Financial Times, Sunday 3 June, 2007. 21. For Ann Lindberg see John Lukas, The Last European War (London: Routledge and Kegan Paul, 1976), Kishore Mahbubani, ‘The Case Against the West’, Foreign Affairs (Vol. 87, No. 3, May/June 2008), p. 111. 22. Lex Rieffel, ‘Why the new President Should Care About the World Bank and the IMF’, The Brookings Institution Research, 19 October 2007, <www.brookings.edu/opinions/2007/1019-multilateral-development-banks.aspx>. 23. Jack Gallagher/John Robinson, Africa and the Victorians: the Official Mind of Imperialism, (London: Macmillan, 1972), p 470. 24. Zakaria, op cit, p. 43. 25. Mark Leonard, Why Europe will run the Twenty-First Century, (London: Fourth Estate, 2006). 26. See Andrew Bacevich, 'Illusions of managing history: the enduring relevance of Reinhold Niebuhr’, Historically Speaking (Vol. 9, No. 3 January/February 2008), pp. 23-27. 27. Dean Acheson, ‘Real and Imagined Handicaps of our Democracy in the Conduct of Foreign Affairs’, Speech given at the HSTL, 31 March 1962. Additional informationNotes on contributorsChristopher Coker Christopher Coker is Professor of International Relations at the London School of Economics. He is the author of The Twilight of the West and, Ethics and War in the 21st Century

The Nation‐Form

It has been said time and again that the paradigm of Third World nationalism is the Hegelian narrative of lordship and bondage – the struggle for recognition. As the hegemonic petty‐bourgeois elite...

Parrhesiatic Games in Turkish Contemporary Art Scene

Click to increase image sizeClick to decrease image size Notes 1 In 2001, they were published in book form, Michel Foucault, Fearless Speech, ed Joseph Pearson, Semiotext(e), Los Angeles 2001, as a text compiled from tape‐recordings made of six lectures delivered in English by Foucault. 2 Alan Milchman and Alan Rosenberg, ‘Michel Foucault: Crises and Problematizations’, Review of Politics, Spring 2005, p 67 3 Michael A Peters, ‘Truth‐telling as an Educational Practice of the Self: Foucault, Parrhesia and the ethics of subjectivity’, Oxford Review of Education, 29:2, 2003. Also see Nancy Luxon, ‘Truthfulness, Risk, and Trust in the Late Lectures of Michel Foucault’, Inquiry, October 2004, 47, pp 464–89 4 Gerald Raunig, ‘The Double Criticism of parrhesia Answering the Question “What is a Progressive (Art) Institution?”’, http://www.republicart.net 5 Foucault, Fearless Speech, op cit, p 17 6 Ibid, p 16 7 ‘He’, because, in ancient Greece parrhesiastes was not only grammatically but also actually always masculine. But Gerald Raunig noted in his article that today, contrary to ancient Greece, both the term and the phenomenon are increasingly addressed in feminist discourses and he gives the example of ‘Postkolonialer Feminismus und die Kunst der Selbstkritik’, in Hito Steyerl and Encarnación Gutiérrez Rodríguez, Spricht die Subalterne deutsch? Migration und postkoloniale Kritik, Münster 2003, pp 270–90. We can also add Valerie Harwood’s use of the term in queer politics: Valerie Harwood, ‘Telling Truths: Wounded Truths and the Activity of Truth Telling’, Discourse: studies in the cultural politics of education, 25:4, December 2004. 8 David R Novak, ‘Engaging Parrhesia in a Democracy: Malcolm X as a Truth‐teller’, Southern Communication Journal, 71:1, March 2006, pp 25–43 9 Foucault, Fearless Speech, op cit, p 16 10 Ibid, p 106 11 Ibid, p 120 12 Ibid, p 17 13 For a detailed discussion of art festivals in Istanbul see Sibel Yardımcı’s related work in: ‘Launching the “Spectacle” in Istanbul: Physical Restructuring, Symbolic Economy, Art Festivals’, 9th EASA Biennial Conference, Bristol University, Bristol, 18–21 September 2006; ‘The New Symbolic Economy of Oriental Cities’, paper presented at the IFEA Conference, Vienna, 6–9 March 2003; and ‘Sponsoring Festivals, Selling Istanbul: Arts Or Market?’, paper presented at Cultural Returns Conference, Open University, Oxford, 18–20 September 2002. 14 Except for a comprehensive critique written by artist Burak Delier in the socialist daily Birgün, ‘Liberal mi radikal mi?’ (Liberal or radical?), Birgün, 11 January 2007. 15 Foucault, Fearless Speech, op cit, p 108 16 Raunig, op cit 17 Ibid 18 Grant H Kester, Conversation Pieces, Community + Communication in Modern Art, University of California Press, Berkeley, 2004, p 6 19 M A Neiwirth, ‘Parrhesia: An Old Word and a New Way of Making News’, Boise State University, 2004, available at: http://www.indymedia.org.uk/media/2004/11/301351.pdf 20 David Graeber, ‘The New Anarchists’, New Left Review, January–February 2002, available at: http://www.newleftreview.net/NLR24704.shtml

Istanbul’s Choice

Click to increase image sizeClick to decrease image size Notes 1 ‘Avrupa yanlıları baskı altında’ (European supporters are stifled), Der Spiegel interview with Orhan Pamuk published at the same time in Radikal, 29 April 2007. 2 Fuat Keyman, ‘Türkiye’nin İki Yüzü, İyi Yönetim ve Sol Siyaset’, Radikal 2, 18 March 2007 3 Çağlar Keyder, ‘Globalisation and Social Exclusion in Istanbul’, International Journal of Urban and Regional Research, 29:1, 2005, p 130 4 A Alp and O Şentürk, ‘İstanbul’da 1 Milyon ev yıkılacak’, Ekonomist, 11 November 2007 5 Quoted in E Boztepe, ‘Topbaş: İstanbul’un trafik sorununu çözmek için 15 milyar dolar lazım’, Radikal, 2 January 2007 6 Murat Güvenç, unpublished manuscript, no date 7 Asu Aksoy and Kevin Robins, ‘Istanbul between Civilisation and Discontent’, New Perspectives on Turkey, no 10, Spring 1994 8 İhsan Bilgin, ‘Kent üretiminin ve kamu yaşamının örgütlenmesinde güncel eğilimler’, Toplum ve Bilim, issue 105, 2006 9 Suzy Menkes, ‘A Futuristic Mall is New Turkish Playground’, International Herald Tribune, 4 December 2006 10 Tom Dyckhoff, ‘Turkey’s New Delights’, Times Online, 15 August 2006 11 İhsan Bilgin, ‘Kent üretiminin ve kamu yaşamının örgütlenmesinde güncel eğilimler’, Toplum ve Bilim, issue 105, 2006 12 IMP, ‘İstanbul Çevre Düzeni Planı: Özet Rapor’, Istanbul, July 2006 13 Orhan Pamuk, ‘My Father’s Suitcase: Nobel Lecture, December 7 2006’, trans Maureen Freely, available at: http://nobelprize.org/nobel_prizes/literature/laureates/2006/pamuk-lecture_en.html (accessed 5 April 2007) 14 Aslı Onat, ‘Dünyaya İstanbul’dan Bakmak’, Milliyet, 15 March 2007 15 Andrew Finkel, ‘İstanbul Modern’, Today’s Zaman, 11 March 2007 16 Neil Brenner and Nik Theodore, ‘Cities and Geographies of “actually existing neoliberalism”’, Antipode, 34, 2002, p 368 17 Orhan Esen, ‘The Tightrope Walk of the Middle Class in a Fractured Istanbul’, Writings from the 9th International Istanbul Biennial, İKSV, Istanbul, 2005 18 Menderes Çınar, ‘Yenilikçi gündem küreselleşmeye mi ihale edildi?’, Görüş, March 2003 19 Neil Smith, ‘New Globalism, New Urbanism: Gentrification as a Global Urban Strategy’, Antipode, 34, 2002 20 Kadir Topbaş, ‘Istanbul için Yeniden Adayim’, Bugün, 20 January 2008 21 Keyder, ‘Globalisation and Social Exclusion in Istanbul’, op cit, p 130 22 D Behar and T İslam, eds, Istanbul’da ‘Soylulaştırma’ (‘Gentrification’ in Istanbul) Bilgi University Publications, İstanbul, 2006; also refer to Işık and Pınarcıoğlu, 2001; Kurtuluş, 2005; Writings from the 9th International Istanbul Biennale, 2005 23 Neil Smith, ‘Which New Urbanism? The Revanchist 90s’, Perspecta, 30, 1999, pp 98–105 24 Keyder, ‘Globalisation and Social Exclusion in Istanbul’, op cit, p 130 25 Brenner and Theodore, op cit, p 376 26 Ibid

A Selective and Potent Oral Inhibitor of the JAK2 Tyrosine Kinase Reverses Polycythemia and Leukocytosis Induced by JAK2 V617F in a Mouse Model.

A somatic mutation (V617F) in the pseudokinase domain of the non-receptor tyrosine kinase JAK2 is found in virtually all patients with the myeloproliferative disease (MPD) polycythemia vera (PV), and about half of those with essential thrombocythemia and chronic idiopathic myelofibrosis. When expressed in mice by retroviral bone marrow transduction and transplantation, JAK2 V617F but not JAK2 wild-type induces leukocytosis with neutrophilia and recapitulates the entire erythroid phenotype of PV, with polycythemia, reticulocytosis, low plasma Epo, and endogenous erythroid colonies (Zaleskas et al., PLoS ONE 2006; 1:e18; Wernig et al., Blood 2006; 107:4274; Lacout et al., Blood 2006; 108:1652). By analogy to BCR-ABL in chronic myeloid leukemia, JAK2 V617F is therefore a rational target for therapy in PV and other JAK2 V617F+ MPDs. Previous studies with a nonselective and parenteral tyrphostin JAK2 inhibitor suggested that short-term inhibition of JAK2 could decrease reticulocytosis in recipients of JAK2 V617F-transduced marrow (Zaleskas et al., op cit.). Here, we studied one of a novel series of inhibitors of JAK2, AZ-01, which potently inhibited JAK2 kinase activity (IC50 < 1nM) and suppressed proliferation of cell lines carrying the JAK2 V617F mutation. We treated cohorts of Balb/c mice with JAK2 V617F-induced polycythemia and leukocytosis with AZ-01 at 10 mg/kg by oral gavage twice daily, or with vehicle alone. After 28 days of treatment, AZ-01-treated mice had significant reductions in hematocrit, hemoglobin, reticulocytes, and splenomegaly, as well as normalization of peripheral blood leukocyte counts (Figure 1). These results demonstrate that oral administration of a potent and selective JAK2 inhibitor can reverse the hematopoietic abnormalities of JAK2 V617F-induced MPD in mice, and validate JAK2 as a target for therapy of human JAK2 V617F+ MPD. [Display omitted] An orally available JAK2 inhibitor decreases the leukocyte count, hematocrit, and reticulocyte count in mice with JAK2 V617F-induced MPD. Leukocyte count (left), hematocrit (center) and reticulocyte counts (right) of cohorts of mice with JAK2 V617F-induced MPD treated with vehicle or drug at 10 mg/kg BID. Blood counts were assessed at 15 and 28 days of treatment. Decreases in d28 hematocrit and retic count in the drug-treated cohorts were significant (p=0.008 and p<0.0001, respectively, t-tests).

Revising the British Army's Counter-Insurgency Doctrine

The Army's counter-insurgency doctrine is published in Part Ten of its Field Manual.1 It was last updated fully in July 2001. The pamphlet is the latest in a line of Army publications that have wre...

Justice delayed or too late for justice? The Khmer Rouge Tribunal and the Cambodian “genocide” 1975–79

The Khmer Rouge under their leader Saloth Sar (“Pol Pot”) were in power in Cambodia between April 1975 and January 1979.1 They came into control of the country after a long and brutal civil war2 an...

Accountability for genocide and other gross human rights violations: the need for an integrated and victim-based transitional justice

The Nuremberg tribunal was the expression and the beginning of states' recognition of their duty to prosecute genocide and other gross human rights violations. It was a first step towards fulfillin...

Rape as genocide: some questions arising

One of the most significant developments in the jurisprudence of modern international criminal law is the determination of the International Criminal Tribunal for Rwanda (ICTR), in the Akayesu case...