Nixon’s Ghost and the Haunting of Violence at Cambodia’s Tuol Sleng Genocide Museum

Between 1975 and 1979, upwards of two million men, women, and children perished in the Cambodian genocide. Decades after the ending of mass violence, Cambodia struggles both with reconciliation and remembrance. These struggles figure prominently in the representation of mass violence at state-sanctioned sites of memorialization, specifically the Tuol Sleng Genocide Museum. In this paper, I draw inspiration from Derrida’s conceptualization of hauntology to provide a critical reading of the Tuol Sleng Genocide Museum. A multivalent concept, haunting directs attention to the traces or remains – whether material or discursive – of violence that remain present in their absence. Consequently, the museum – a popular destination on the dark tourism circuit – reproduces a particular knowledge of Cambodia’s genocide, that is, a state-sanctioned interpretation of Khmer Rouge violence. At the same time, the historical and geopolitical context of the genocide, notably the extension of the United States-led war in Vietnam, haunts the museum’s display of violence by its conspicuous absence. In doing so, I provide a critique of epistemological practices at the Tuol Sleng Genocide Museum and highlight the tension of absent-presences that haunt the display of genocidal violence in Cambodia.Between 1975 and 1979, upwards of two million men, women, and children perished in the Cambodian genocide. Decades after the ending of mass violence, Cambodia struggles both with reconciliation and remembrance. These struggles figure prominently in the representation of mass violence at state-sanctioned sites of memorialization, specifically the Tuol Sleng Genocide Museum. In this paper, I draw inspiration from Derrida’s conceptualization of hauntology to provide a critical reading of the Tuol Sleng Genocide Museum. A multivalent concept, haunting directs attention to the traces or remains – whether material or discursive – of violence that remain present in their absence. Consequently, the museum – a popular destination on the dark tourism circuit – reproduces a particular knowledge of Cambodia’s genocide, that is, a state-sanctioned interpretation of Khmer Rouge violence. At the same time, the historical and geopolitical context of the genocide, notably the extension of the United States-led war in Vietnam, haunts the museum’s display of violence by its conspicuous absence. In doing so, I provide a critique of epistemological practices at the Tuol Sleng Genocide Museum and highlight the tension of absent-presences that haunt the display of genocidal violence in Cambodia

Nixon’s Ghost and the Haunting of Violence at Cambodia’s Tuol Sleng Genocide Museum

Between 1975 and 1979, upwards of two million men, women, and children perished in the Cambodian genocide. Decades after the ending of mass violence, Cambodia struggles both with reconciliation and remembrance. These struggles figure prominently in the representation of mass violence at state-sanctioned sites of memorialization, specifically the Tuol Sleng Genocide Museum. In this paper, I draw inspiration from Derrida’s conceptualization of hauntology to provide a critical reading of the Tuol Sleng Genocide Museum. A multivalent concept, haunting directs attention to the traces or remains – whether material or discursive – of violence that remain present in their absence. Consequently, the museum – a popular destination on the dark tourism circuit – reproduces a particular knowledge of Cambodia’s genocide, that is, a state-sanctioned interpretation of Khmer Rouge violence. At the same time, the historical and geopolitical context of the genocide, notably the extension of the United States-led war in Vietnam, haunts the museum’s display of violence by its conspicuous absence. In doing so, I provide a critique of epistemological practices at the Tuol Sleng Genocide Museum and highlight the tension of absent-presences that haunt the display of genocidal violence in Cambodia

Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms

Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC50) of <1 n, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC50=11–120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs

Growth Arrest of BCR-ABL Positive Cells with a Sequence-Specific Polyamide-Chlorambucil Conjugate

Chronic myeloid leukemia (CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, has significantly improved the clinical outcome of patients with CML. However, subsets of patients lose their response to treatment through the emergence of imatinib-resistant cells, and imatinib treatment is less durable for patients with late stage CML. Although alternative Bcr-Abl tyrosine kinase inhibitors have been developed to overcome drug resistance, a cocktail therapy of different kinase inhibitors and additional chemotherapeutics may be needed for complete remission of CML in some cases. Chlorambucil has been used for treatment of B cell chronic lymphocytic leukemia, non-Hodgkin's and Hodgkin's disease. Here we report that a DNA sequence-specific pyrrole-imidazole polyamide-chlorambucil conjugate, 1R-Chl, causes growth arrest of cells harboring both unmutated BCR-ABL and three imatinib resistant strains. 1R-Chl also displays selective toxicities against activated lymphocytes and a high dose tolerance in a murine model

A novel signalling screen demonstrates that CALR mutations activate essential MAPK signalling and facilitate megakaryocyte differentiation.

Most MPN patients lacking JAK2 mutations harbour somatic CALR mutations that are thought to activate cytokine signalling although the mechanism is unclear. To identify kinases important for survival of CALR-mutant cells we developed a novel strategy (KISMET) which utilises the full range of kinase selectivity data available from each inhibitor and thus takes advantage of off-target noise that limits conventional siRNA or inhibitor screens. KISMET successfully identified known essential kinases in haematopoietic and non-haematopoietic cell lines and identified the MAPK pathway as required for growth of the CALR-mutated MARIMO cells. Expression of mutant CALR in murine or human haematopoietic cell lines was accompanied by MPL-dependent activation of MAPK signalling, and MPN patients with CALR mutations showed increased MAPK activity in CD34-cells, platelets and megakaryocytes. Although CALR mutations resulted in protein instability and proteosomal degradation, mutant CALR was able to enhance megakaryopoiesis and pro-platelet production from human CD34+ progenitors. These data link aberrant MAPK activation to the MPN phenotype and identify it as a potential therapeutic target in CALR-mutant positive MPNs.Leukemia accepted article preview online, 14 October 2016. doi:10.1038/leu.2016.280.Work in the Green lab is supported by Leukemia and Lymphoma Research, Cancer Research UK, the NIHR Cambridge Biomedical Research Centre, the Cambridge Experimental Cancer Medicine Centre and the Leukemia & Lymphoma Society of America. WW is supported by the Austrian Science Foundation (J 3578-B21). CGA is supported by Kay Kendall Leukaemia Fund clinical research fellowship. UM is supported by a Cancer Research UK Clinician Scientist Fellowship. Work in the Huntly lab is supported by the European Research Council, the MRC (UK), Bloodwise, the Cambridge NIHR funded BRC, KKLF and a WT/MRC Stem Cell centre grant. Work in the Green and Huntly Labs is supported by core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research (100140/z/12/z) and Wellcome Trust-MRC Cambridge Stem Cell Institute (097922/Z/11/Z)

From old organisms to new molecules: integrative biology and therapeutic targets in accelerated human ageing

Understanding the basic biology of human ageing is a key milestone in attempting to ameliorate the deleterious consequences of old age. This is an urgent research priority given the global demographic shift towards an ageing population. Although some molecular pathways that have been proposed to contribute to ageing have been discovered using classical biochemistry and genetics, the complex, polygenic and stochastic nature of ageing is such that the process as a whole is not immediately amenable to biochemical analysis. Thus, attempts have been made to elucidate the causes of monogenic progeroid disorders that recapitulate some, if not all, features of normal ageing in the hope that this may contribute to our understanding of normal human ageing. Two canonical progeroid disorders are Werner’s syndrome and Hutchinson-Gilford progeroid syndrome (also known as progeria). Because such disorders are essentially phenocopies of ageing, rather than ageing itself, advances made in understanding their pathogenesis must always be contextualised within theories proposed to help explain how the normal process operates. One such possible ageing mechanism is described by the cell senescence hypothesis of ageing. Here, we discuss this hypothesis and demonstrate that it provides a plausible explanation for many of the ageing phenotypes seen in Werner’s syndrome and Hutchinson-Gilford progeriod syndrome. The recent exciting advances made in potential therapies for these two syndromes are also reviewed

The Freedom Budget at 45: Functional Finance and Full Employment

Forty-five years ago, the A. Philip Randolph Institute issued The Freedom Budget, in which a program for economic transformation was proposed that included a job guarantee for everyone ready and willing to work, a guaranteed income for those unable to work or those who should not be working, and a living wage to lift the working poor out of poverty. Such policies were supported by a host of scholars, civic leaders, and institutions, including the Rev. Dr. Martin Luther King Jr.; indeed, they provided the cornerstones for King's Poor Peoples' Campaign and economic bill of rights. This paper proposes a New Freedom Budget for full employment based on the principles of functional finance. To counter a major obstacle to such a policy program, the paper includes a primer on three paradigms for understanding government budget deficits and the national debt: the deficit hawk, deficit dove, and functional finance perspectives. Finally, some of the benefits of the job guarantee are outlined, including the ways in which the program may serve as a vehicle for a variety of social policies