264 research outputs found

    Convicts and coolies : rethinking indentured labour in the nineteenth century

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    This article seeks to shift the frame of analysis within which discussions of Indian indentured migration take place. It argues that colonial discourses and practices of indenture are best understood not with regard to the common historiographical framework of whether it was 'a new system of slavery', but in the context of colonial innovations in incarceration and confinement. The article shows how Indian experiences of and knowledge about transportation overseas to penal settlements informed in important ways both their own understandings and representations of migration and the colonial practices associated with the recruitment of indentured labour. In detailing the connections between two supposedly different labour regimes, it thus brings a further layer of complexity to debates around their supposed distinctions

    Synergistic induction of apoptosis by simultaneous disruption of the Bcl-2 and MEK/MAPK pathways in acute myelogenous leukemia

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    : Recent studies suggest that the Bcl-2 and mitogen-activated protein kinase (MAPK) pathways together confer an aggressive, apoptosis-resistant phenotype on acute myelogenous leukemia (AML) cells. In this study, we analyzed the effects of simultaneous inhibition of these 2 pathways. In AML cell lines with constitutively activated MAPK, MAPK kinase (MEK) blockade by PD184352 strikingly potentiated the apoptosis induced by the small-molecule Bcl-2 inhibitor HA14-1 or by Bcl-2 antisense oligonucleotides. Isobologram analysis confirmed the synergistic nature of this interaction. Moreover, MEK blockade overcame Bcl-2 overexpression-mediated resistance to the proapoptotic effects of HA14-1. Most importantly, simultaneous exposure to PD184352 significantly (P =.01) potentiated HA14-1-mediated inhibition of clonogenic growth in all primary AML samples tested. These findings show that the Bcl-2 and MAPK pathways are relevant molecular targets in AML and that their concurrent inhibition could be developed into a new therapeutic strategy for this disease

    Colour reconnection in e+e- -> W+W- at sqrt(s) = 189 - 209 GeV

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    The effects of the final state interaction phenomenon known as colour reconnection are investigated at centre-of-mass energies in the range sqrt(s) ~ 189-209 GeV using the OPAL detector at LEP. Colour reconnection is expected to affect observables based on charged particles in hadronic decays of W+W-. Measurements of inclusive charged particle multiplicities, and of their angular distribution with respect to the four jet axes of the events, are used to test models of colour reconnection. The data are found to exclude extreme scenarios of the Sjostrand-Khoze Type I (SK-I) model and are compatible with other models, both with and without colour reconnection effects. In the context of the SK-I model, the best agreement with data is obtained for a reconnection probability of 37%. Assuming no colour reconnection, the charged particle multiplicity in hadronically decaying W bosons is measured to be (nqqch) = 19.38+-0.05(stat.)+-0.08 (syst.).Comment: 30 pages, 9 figures, Submitted to Euro. Phys. J.

    Search for the Standard Model Higgs Boson with the OPAL Detector at LEP

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    This paper summarises the search for the Standard Model Higgs boson in e+e- collisions at centre-of-mass energies up to 209 GeV performed by the OPAL Collaboration at LEP. The consistency of the data with the background hypothesis and various Higgs boson mass hypotheses is examined. No indication of a signal is found in the data and a lower bound of 112.7GeV/C^2 is obtained on the mass of the Standard Model Higgs boson at the 95% CL.Comment: 51 pages, 21 figure

    Measurement of the Hadronic Photon Structure Function F_2^gamma at LEP2

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    The hadronic structure function of the photon F_2^gamma is measured as a function of Bjorken x and of the factorisation scale Q^2 using data taken by the OPAL detector at LEP. Previous OPAL measurements of the x dependence of F_2^gamma are extended to an average Q^2 of 767 GeV^2. The Q^2 evolution of F_2^gamma is studied for average Q^2 between 11.9 and 1051 GeV^2. As predicted by QCD, the data show positive scaling violations in F_2^gamma. Several parameterisations of F_2^gamma are in agreement with the measurements whereas the quark-parton model prediction fails to describe the data.Comment: 4 pages, 2 figures, to appear in the proceedings of Photon 2001, Ascona, Switzerlan

    Search for R-Parity Violating Decays of Scalar Fermions at LEP

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    A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

    Selective anti-Leishmanial Strathclyde minor groove binders using an N-oxide tail group modification

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    The neglected tropical disease leishmaniasis, caused by Leishmania spp., is becoming more problematic due to the emergence of drug-resistant strains. Therefore, new drugs to treat leishmaniasis, with novel mechanisms of action, are urgently required. Strathclyde minor groove binders (S-MGBs) are an emerging class of anti-infective agent that have been shown to have potent activity against various bacteria, viruses, fungi and parasites. Herein, it is shown that S-MGBs have potent activity against L. donovani, and that an N-oxide derivation of the tertiary amine tail of typical S-MGBs leads to selective anti-leishmanial activity. Additionally, using S-MGB-219, the N-oxide derivation is shown to retain strong binding to DNA as a 2:1 dimer. These findings support the further study of anti-leishmanial S-MGBs as novel therapeutics

    Chronic treatment with 17-DMAG improves balance and coordination in a new mouse model of Machado-Joseph disease

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    Machado-Joseph disease (MJD) or spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disease currently with no treatment. We describe a novel mouse model of MJD which expresses mutant human ataxin-3 at near endogenous levels and manifests MJD-like motor symptoms that appear gradually and progress over time. CMVMJD135 mice show ataxin-3 intranuclear inclusions in the CNS and neurodegenerative changes in key disease regions, such as the pontine and dentate nuclei. Hsp90 inhibition has shown promising outcomes in some neurodegenerative diseases, but nothing is known about its effects in MJD. Chronic treatment of CMVMJD mice with Hsp90 inhibitor 17-DMAG resulted in a delay in the progression of their motor coordination deficits and, at 22 and 24 weeks of age, was able to rescue the uncoordination phenotype to wild-type levels; in parallel, a reduction in neuropathology was observed in treated animals. We observed limited induction of heat-shock proteins with treatment, but found evidence that 17-DMAG may be acting through autophagy, as LC3-II (both at mRNA and protein levels) and beclin-1 were induced in the brain of treated animals. This resulted in decreased levels of the mutant ataxin-3 and reduced intranuclear aggregation of this protein. Our data validate this novel mouse model as a relevant tool for the study of MJD pathogenesis and for pre-clinical studies, and show that Hsp90 inhibition is a promising therapeutic strategy for MJD.We would like to thank to Dr. Henry Paulson for providing the anti-ataxin-3 serum, Dr. Monica Sousa for the pCMV vector and to Eng. Lucilia Goreti Pinto, Lu s Martins, Miguel Carneiro and Celina Barros for technical assistance. This work was supported by Fundacao para a Ciencia e Tecnologia through the projects FEDER/FCT, POCI/SAU-MMO/60412/2004 and PTDC/SAU-GMG/64076/2006. This work was supported by Fundacao para a Ciencia e Tecnologia through fellowships SFRH/BPD/91562/2012 to A.S-F., SFRH/BD/78388/2011 to S. D-S., SFRH/BD/51059/2010 to A.N-C., and SFRH/BPD/79469/2011 to A.T-C.