63 research outputs found

    Continental flood basalts derived from the hydrous mantle transition zone

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    It has previously been postulated that the Earth's hydrous mantle transition zone may play a key role in intraplate magmatism, but no confirmatory evidence has been reported. Here we demonstrate that hydrothermally altered subducted oceanic crust was involved in generating the late Cenozoic Chifeng continental flood basalts of East Asia. This study combines oxygen isotopes with conventional geochemistry to provide evidence for an origin in the hydrous mantle transition zone. These observations lead us to propose an alternative thermochemical model, whereby slab-triggered wet upwelling produces large volumes of melt that may rise from the hydrous mantle transition zone. This model explains the lack of pre-magmatic lithospheric extension or a hotspot track and also the arc-like signatures observed in some large-scale intracontinental magmas. Deep-Earth water cycling, linked to cold subduction, slab stagnation, wet mantle upwelling and assembly/breakup of supercontinents, can potentially account for the chemical diversity of many continental flood basalts

    CD4-Independent Human Immunodeficiency Virus Infection Involves Participation of Endocytosis and Cathepsin B

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    During a comparison of the infectivity of mNDK, a CD4-independent human immunodeficiency virus type 1 (HIV-1) strain, to various cell lines, we found that HeLa cells were much less susceptible than 293T and TE671 cells. Hybridoma cells between HeLa and 293T cells were as susceptible as 293T cells, suggesting that cellular factors enhance the mNDK infection in 293T cells. By screening a cDNA expression library in HeLa cells, cystatin C was isolated as an enhancer of the mNDK infection. Because cathepsin B protease, a natural ligand of cystatin C, was upregulated in HeLa cells, we speculated that the high levels of cathepsin B activities were inhibitory to the CD4-independent infection and that cystatin C enhanced the infection by impairing the excessive cathepsin B activity. Consistent with this idea, pretreatment of HeLa cells with 125 µM of CA-074Me, a cathepsin B inhibitor, resulted in an 8-fold enhancement of the mNDK infectivity. Because cathepsin B is activated by low pH in acidic endosomes, we further examined the potential roles of endosomes in the CD4-independent infection. Suppression of endosome acidification or endocytosis by inhibitors or by an Eps15 dominant negative mutant reduced the infectivity of mNDK in which CD4-dependent infections were not significantly impaired. Taken together, these results suggest that endocytosis, endosomal acidification, and cathepsin B activity are involved in the CD4-independent entry of HIV-1

    Catching-up in the global factory: analysis and policy implications

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    MNEs shape the location of activities in the world economy, linking diverse regions in what has been called the global factory. This study portrays the evolution of incomes and employment in the global factory using a quantitative input–output approach. We find emerging economies forging ahead relative to advanced economies in income derived from fabrication activities, handling the physical transformation process of goods. In contrast, convergence in income derived from knowledge-intensive activities carried out in pre- and post-fabrication stages is much slower. We discuss possible barriers to catching-up and policy implications for emerging economies in developing innovation capabilities, stressing the pivotal role of MNEs

    Adoption of an “Open” Envelope Conformation Facilitating CD4 Binding and Structural Remodeling Precedes Coreceptor Switch in R5 SHIV-Infected Macaques

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    A change in coreceptor preference from CCR5 to CXCR4 towards the end stage disease in some HIV-1 infected individuals has been well documented, but the reasons and mechanisms for this tropism switch remain elusive. It has been suggested that envelope structural constraints in accommodating amino acid changes required for CXCR4 usage is an obstacle to tropism switch, limiting the rate and pathways available for HIV-1 coreceptor switching. The present study was initiated in two R5 SHIVSF162P3N-infected rapid progressor macaques with coreceptor switch to test the hypothesis that an early step in the evolution of tropism switch is the adoption of a less constrained and more “open” envelope conformation for better CD4 usage, allowing greater structural flexibility to accommodate further mutational changes that confer CXCR4 utilization. We show that, prior to the time of coreceptor switch, R5 viruses in both macaques evolved to become increasingly sCD4-sensitive, suggestive of enhanced exposure of the CD4 binding site and an “open” envelope conformation, and this correlated with better gp120 binding to CD4 and with more efficient infection of CD4low cells such as primary macrophages. Moreover, significant changes in neutralization sensitivity to agents and antibodies directed against functional domains of gp120 and gp41 were seen for R5 viruses close to the time of X4 emergence, consistent with global changes in envelope configuration and structural plasticity. These observations in a simian model of R5-to-X4 evolution provide a mechanistic basis for the HIV-1 coreceptor switch

    Silicon in magnetite: High resolution microanalysis of magnetite-ilmenite intergrowths

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    Magnetite-ilmenite “oxidation-exsolution” intergrowths from an original titanomagnetite microphenocryst from an ash flow tuff unit have been studied using conventional transmission electron microscopy and analytical electron microscopy. Silicon has been found to be in solid solution in all of the magnetite studied and in some of the coexisting ilmenite. The average value in magnetite is 1.2 wt.% Si, equivalent to solid solution of 9 mole % Fe 2 SiO 4 . Silicon is also present in very small silicate inclusions and as unusual Si-rich domains of uncertain origin in magnetite. The inclusions and domains may be irregularly distributed through the magnetite in sizes well below those resolvable with the electron microprobe. Microprobe analyses for Si in magnetite generally reflect these heterogeneities in addition to a component presumably in solid solution. The petrologic implications of the data can be assessed only when relevant thermochemical data become available and the distribution of Si in magnetite is better understood.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47334/1/410_2004_Article_BF00378006.pd

    A systematic review of cluster randomised trials in residential facilities for older people suggests how to improve quality.

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    BACKGROUND: Previous reviews of cluster randomised trials have been critical of the quality of the trials reviewed, but none has explored determinants of the quality of these trials in a specific field over an extended period of time. Recent work suggests that correct conduct and reporting of these trials may require more than published guidelines. In this review, our aim was to assess the quality of cluster randomised trials conducted in residential facilities for older people, and to determine whether (1) statistician involvement in the trial and (2) strength of journal endorsement of the Consolidated Standards of Reporting Trials (CONSORT) statement influence quality. METHODS: We systematically identified trials randomising residential facilities for older people, or parts thereof, without language restrictions, up to the end of 2010, using National Library of Medicine (Medline) via PubMed and hand-searching. We based quality assessment criteria largely on the extended CONSORT statement for cluster randomised trials. We assessed statistician involvement based on statistician co-authorship, and strength of journal endorsement of the CONSORT statement from journal websites. RESULTS: 73 trials met our inclusion criteria. Of these, 20 (27%) reported accounting for clustering in sample size calculations and 54 (74%) in the analyses. In 29 trials (40%), methods used to identify/recruit participants were judged by us to have potentially caused bias or reporting was unclear to reach a conclusion. Some elements of quality improved over time but this appeared not to be related to the publication of the extended CONSORT statement for these trials. Trials with statistician/epidemiologist co-authors were more likely to account for clustering in sample size calculations (unadjusted odds ratio 5.4, 95% confidence interval 1.1 to 26.0) and analyses (unadjusted OR 3.2, 1.2 to 8.5). Journal endorsement of the CONSORT statement was not associated with trial quality. CONCLUSIONS: Despite international attempts to improve methods in cluster randomised trials, important quality limitations remain amongst these trials in residential facilities. Statistician involvement on trial teams may be more effective in promoting quality than further journal endorsement of the CONSORT statement. Funding bodies and journals should promote statistician involvement and co-authorship in addition to adherence to CONSORT guidelines
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