377 research outputs found

    The Influence of Lubrication on Electrical and Mechanical Parameters of Potentiometer Resistive Element

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    Fixed resistors are usually protected against environmental influences. For this aim, special lacquers are used. Much of the environmental qualities of such a resistor are directly related to its enclosure

    Global unions: chasing the dream or building the reality?

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    This article takes as its theme the global restructuring of capital and its impact on worker organization. It argues for a reassertion of class in any analysis of global solidarity, and assesses the opportunities and barriers to effective global unionization. Rooted in the UK experience, the article analyzes the impact of the European social dimension on trade unions, before taking the discussion into a global dimension. It concludes by suggesting that there are reasons for cautious optimism in terms of solidarity building, despite difficult historical legacies and the common replacement of action with rhetoric

    The hepatitis E virus ORF1 hypervariable region confers partial cyclophilin dependency

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    Hepatitis E virus (HEV) is an emerging pathogen responsible for more than 20 million cases of acute hepatitis globally per annum. Healthy individuals typically have a self-limiting infection, but mortality rates in some populations such as pregnant women can reach 30 %. A detailed understanding of the virus lifecycle is lacking, mainly due to limitations in experimental systems. In this regard, the cyclophilins are an important family of proteins that have peptidyl-prolyl isomerase activity and play roles in the replication of a number of positive-sense RNA viruses, including hepatotropic viruses such as hepatitis C virus (HCV). Cyclophilins A and B (CypA/B) are the two most abundant Cyps in hepatocytes and are therefore potential targets for pan-viral therapeutics. Here, we investigated the importance of CypA and CypB for HEV genome replication using sub-genomic replicons. Using a combination of pharmacological inhibition by cyclosporine A (CsA), and silencing by small hairpin RNA we find that CypA and CypB are not essential for HEV replication. However, we find that silencing of CypB reduces replication of some HEV isolates in some cells. Furthermore, sensitivity to Cyp silencing appears to be partly conferred by the sequence within the hypervariable region of the viral polyprotein. These data suggest HEV is atypical in its requirements for cyclophilin for viral genome replication and that this phenomenon could be genotype- and sequence-specific

    Genetic Economy in Picornaviruses: Foot-and-Mouth Disease Virus Replication Exploits Alternative Precursor Cleavage Pathways

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    The RNA genomes of picornaviruses are translated into single polyproteins which are subsequently cleaved into structural and non-structural protein products. For genetic economy, proteins and processing intermediates have evolved to perform distinct functions. The picornavirus precursor protein, P3, is cleaved to produce membrane-associated 3A, primer peptide 3B, protease 3Cpro and polymerase 3Dpol. Uniquely, foot-and-mouth disease virus (FMDV) encodes three similar copies of 3B (3B1-3), thus providing a convenient natural system to explore the role(s) of 3B in the processing cascade. Using a replicon system, we confirmed by genetic deletion or functional inactivation that each copy of 3B appears to function independently to prime FMDV RNA replication. However, we also show that deletion of 3B3 prevents replication and that this could be reversed by introducing mutations at the C-terminus of 3B2 that restored the natural sequence at the 3B3-3C cleavage site. In vitro translation studies showed that precursors with 3B3 deleted were rapidly cleaved to produce 3CD but that no polymerase, 3Dpol, was detected. Complementation assays, using distinguishable replicons bearing different inactivating mutations, showed that replicons with mutations within 3Dpol could be recovered by 3Dpol derived from “helper” replicons (incorporating inactivation mutations in all three copies of 3B). However, complementation was not observed when the natural 3B-3C cleavage site was altered in the “helper” replicon, again suggesting that a processing abnormality at this position prevented the production of 3Dpol. When mutations affecting polyprotein processing were introduced into an infectious clone, viable viruses were recovered but these had acquired compensatory mutations in the 3B-3C cleavage site. These mutations were shown to restore the wild-type processing characteristics when analysed in an in vitro processing assay. Overall, this study demonstrates a dual functional role of the small primer peptide 3B3, further highlighting how picornaviruses increase genetic economy

    International Public Health Research Involving Interpreters: a Case Study from Bangladesh

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    Background: Cross-cultural and international research are important components of public health research, but the challenges of language barriers and working with interpreters are often overlooked, particularly in the case of qualitative research. Methods: A case-study approach was used to explore experiences of working with an interpreter in Bangladesh as part of a research project investigating women's experiences of emergency obstetric care. The case study: Data from the researcher's field notes provided evidence of experiences in working with an interpreter and show how the model of interviewing was adapted over time to give a more active role to the interpreter. The advantages of a more active role were increased rapport and "flow" in interviews. The disadvantages included reduced control from the researcher's perspective. Some tensions between the researcher and interpreter remained hard to overcome, irrespective of the model used. Independent transcription and translation of the interviews also raised questions around accuracy in translation. Conclusion: The issues examined in this case study have broader implications for public health research. Further work is needed in three areas: 1) developing effective relationships with interpreters; 2) the impact of the interpreter on the research process; and 3) the accuracy of the translation and level of analysis needed in any specific public health research. Finally, this paper highlights the importance to authors of reflecting on the potential impact of translation and interpretation on the research process when disseminating their research

    Re-embedding agency at the workplace scale: workers and labour control in Glasgow call centres

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    Following recent calls for the development of a more embedded sense of labour agency, this paper focuses on the scale of the workplace which is largely absent from recent labour geography debates. Drawing on studies in the labour process tradition, the paper presents empirical research on call centre work in Glasgow, utilising this to revisit the concept of local Labour Control Regimes (LCR). We argue that rather than being simply imposed by capital and the state ‘from above’, workplace control should be seen as the product of a dialectical process of interaction and negotiation between management and labour. Labour’s indeterminacy can influence capital in case specific ways as firms adapt to labour agency and selectively tolerate and collude with certain practices and behaviours. Workers’ learned behaviour and identities are shown to affect not only recruitment patterns in unexpected ways, but also modes of accepted conduct in call centres. Accordingly, the case is made for the influence of subtle – yet pervasive – worker agency expressed at the micro-scale of the labour process itself. This, it is argued, exerts a degree of ‘bottom-up’ pressure on key fractions of capital within the local LCR

    BCL-2 family protein expression and platinum drug resistance in ovarian carcinoma

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    The expression of the BCL-2 family proteins, BCL-2, BAX, BCLXLand BAK have been determined in a panel of 12 human ovarian carcinoma cell lines encompassing a wide range in sensitivity to cisplatin. Whereas BAX, BCLXLand BAK levels did not correlate with sensitivity, there was a statistically significant inverse correlation (r = –0.81;P = 0.002) between growth inhibition by cisplatin and BCL-2 levels. In sublines possessing acquired resistance to various platinum-based drugs or across a panel of human ovarian carcinoma xenografts, there was no consistent pattern of BCL-2 expression. Two relatively sensitive lines (A2780 and CH1) have been stably transfected with bcl-2 and bclXLrespectively and two relatively resistant lines (A2780cisR and SKOV-3) stably transfected with bax. Overexpression of BCL-2 in A2780 cells led to resistance to cisplatin compared to the vector control when assayed at 48 h post-drug incubation but a significant increase in sensitivity at 96 h. Relative rates of apoptosis at 48- and 96-h post-cisplatin exposure mirrored the growth inhibition. There was no significant difference in sensitivity of the pair of lines by clonogenic assay. No significant changes in chemosensitivity to a variety of DNA-damaging or tubulin-interactive agents were observed in the remaining transfected lines. Taken together, these results suggest that, in human ovarian carcinoma cells, high BCL-2 levels (either naturally occurring or through gene transfection) confers a trend towards sensitivity not resistance to platinum drugs. © 2000 Cancer Research Campaig

    Dynamics in the murine norovirus capsid revealed by high-resolution cryo-EM

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    Icosahedral viral capsids must undergo conformational rearrangements to coordinate essential processes during the viral life cycle. Capturing such conformational flexibility has been technically challenging yet could be key for developing rational therapeutic agents to combat infections. Noroviruses are nonenveloped, icosahedral viruses of global importance to human health. They are a common cause of acute gastroenteritis, yet no vaccines or specific antiviral agents are available. Here, we use genetics and cryo-electron microscopy (cryo-EM) to study the high-resolution solution structures of murine norovirus as a model for human viruses. By comparing our 3 structures (at 2.9- to 3.1-Å resolution), we show that whilst there is little change to the shell domain of the capsid, the radiating protruding domains are flexible, adopting distinct states both independently and synchronously. In doing so, the capsids sample a range of conformational space, with implications for maintaining virion stability and infectivity

    Transnational social capital: the socio‐spatialities of civil society

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    Civil society remains a contested concept, but one that is widely embedded in global development processes. Transnationalism within civil society scholarship is often described dichotomously, either through hierarchical dependency relations or as a more amorphous networked global civil society. These two contrasting spatial imaginaries produce very particular ideas about how transnational relations contribute to civil society. Drawing on empirical material from research with civil society organizations in Barbados and Grenada, in this article I contend that civil society groups use forms of transnational social capital in their work. This does not, however, resonate with the horizontal relations associated with grassroots globalization or vertical chains of dependence. These social relations are imbued with power and agency and are entangled in situated historical, geographical and personal contexts. I conclude that the diverse transnational social relations that are part of civil society activity offer hope and possibilities for continued civil society action in these unexpected spatial arrangements
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