633 research outputs found

    Acoustic Emission Monitoring of Fatigue Damage in Metals

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    Acoustic emission (AE) consists of high frequency stress waves generated by the rapid release of energy due to fracture, plastic deformation, wear or interfacial friction [1]. Acoustic emission monitoring is a very sensitive method with a wide dynamic range and can be used as a diagnostic means of continuous assessment of damage in materials and components. Acoustic emission methods can be applied to metallic components and specimens subjected to monotonic or fatigue loading. In general, acoustic emission can be used to monitor crack initiation and propagation and to locate the source of the emission

    Exhausted CD4âș T Cells during Malaria Exhibit Reduced mTORc1 Activity Correlated with Loss of T-bet Expression

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    CD4âș T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control and infection chronicity. However, the mechanisms of CD4âș T cell exhaustion are still poorly understood. In this study, we show that Ag-experienced (Ag-exp) CD4âș T cell exhaustion during Plasmodium yoelii nonlethal infection occurs alongside the reduction in mammalian target of rapamycin (mTOR) activity and restriction in CD4+ T cell glycolytic capacity. We demonstrate that the loss of glycolytic metabolism and mTOR activity within the exhausted Ag-expCD4âș T cell population during infection coincides with reduction in T-bet expression. T-bet was found to directly bind to and control the transcription of various mTOR and metabolism-related genes within effector CD4âș T cells. Consistent with this, Ag-expTh1 cells exhibited significantly higher and sustained mTOR activity than effector T-bet- (non-Th1) Ag-expT cells throughout the course of malaria. We identified mTOR to be redundant for sustaining T-bet expression in activated Th1 cells, whereas mTOR was necessary but not sufficient for maintaining IFN-Îł production by Th1 cells. Immunotherapy targeting PD-1, CTLA-4, and IL-27 blocked CD4âș T cell exhaustion during malaria infection and was associated with elevated T-bet expression and a concomitant increased CD4âș T cell glycolytic metabolism. Collectively, our data suggest that mTOR activity is linked to T-bet in Ag-expCD4âș T cells but that reduction in mTOR activity may not directly underpin Ag-expTh1 cell loss and exhaustion during malaria infection. These data have implications for therapeutic reactivation of exhausted CD4âș T cells during malaria infection and other chronic conditions

    The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

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    Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

    Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

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    Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

    ‘Berrypicking’ in the formation of ideas about problem drinking amongst users of alcohol online support groups

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    Beliefs held by individuals about the illnesses or problems that affect them have been shown to impact upon the health and other outcomes that they achieve. Online support groups (OSGs) are one source of information used by those with health problems which may influence or determine what they think about their particular issue and how to resolve it. Problem drinking remains a major source of significant costs to society. This article explores whether the discussion forums of alcohol OSGs that do not follow the 12-step philosophy of Alcoholics Anonymous influence the formation of these beliefs, reporting on the outcome of thematic analysis of interviews with 25 users from five groups. It argues that Bates’ ‘Berrypicking’ model of information searching is helpful in illuminating group members’ information seeking activities. It looks at the four key aspects of berrypicking identified by Bates – the nature of the search query, the information ‘domains’ drawn on, the information retrieved and the search techniques used. The study finds that users are typically berrypickers, selecting information from different sources and forming their own interpretations

    A survey of sports drinks consumption amongst adolescents

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    Background Sports drinks intended to improve performance and hydrate athletes taking part in endurance sport are being marketed to children, for whom these products are not intended. Popularity among children has grown exponentially. Worryingly they consume them socially, as well as during physical activity. Sports drinks are high in sugar and are acidic. Product marketing ignores the potential harmful effects of dental caries and erosion. Objective To investigate the use of sports drinks by children. Method One hundred and eighty-three self-complete questionnaires were distributed to four schools in South Wales. Children in high school years 8 and 9 (aged 12–14) were recruited to take part. Questions focused on use of sports drinks, type consumed, frequency of and reason for consumption and where drinks were purchased. Results One hundred and sixty children responded (87% response rate): 89.4% (143) claimed to drink sports drinks, half drinking them at least twice a week. Lucozade Sportℱ was the most popular brand. The main reason for consuming the drinks was attributed to the 'nice taste' (90%, 129/143). Most respondents purchased the drinks from local shops (80.4%, 115) or supermarkets (54.5%, 78). More boys claimed to drink sports drinks during physical activity (77.9% versus 48.6% girls, P <0.001). Whereas more girls claimed to drink them socially (51.4% versus 48.5% boys, NS). Conclusion A high proportion of children consumed sports drinks regularly and outside of sporting activity. Dental health professionals should be aware of the popularity of sports drinks with children when giving health education advice or designing health promotion initiatives

    First Neutrino Observations from the Sudbury Neutrino Observatory

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    The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

    High genetic diversity at the extreme range edge: nucleotide variation at nuclear loci in Scots pine (Pinus sylvestris L.) in Scotland

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    Nucleotide polymorphism at 12 nuclear loci was studied in Scots pine populations across an environmental gradient in Scotland, to evaluate the impacts of demographic history and selection on genetic diversity. At eight loci, diversity patterns were compared between Scottish and continental European populations. At these loci, a similar level of diversity (Ξsil=~0.01) was found in Scottish vs mainland European populations, contrary to expectations for recent colonization, however, less rapid decay of linkage disequilibrium was observed in the former (ρ=0.0086±0.0009, ρ=0.0245±0.0022, respectively). Scottish populations also showed a deficit of rare nucleotide variants (multi-locus Tajima's D=0.316 vs D=−0.379) and differed significantly from mainland populations in allelic frequency and/or haplotype structure at several loci. Within Scotland, western populations showed slightly reduced nucleotide diversity (πtot=0.0068) compared with those from the south and east (0.0079 and 0.0083, respectively) and about three times higher recombination to diversity ratio (ρ/Ξ=0.71 vs 0.15 and 0.18, respectively). By comparison with results from coalescent simulations, the observed allelic frequency spectrum in the western populations was compatible with a relatively recent bottleneck (0.00175 × 4Ne generations) that reduced the population to about 2% of the present size. However, heterogeneity in the allelic frequency distribution among geographical regions in Scotland suggests that subsequent admixture of populations with different demographic histories may also have played a role

    Electron Antineutrino Search at the Sudbury Neutrino Observatory

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    Upper limits on the \nuebar flux at the Sudbury Neutrino Observatory have been set based on the \nuebar charged-current reaction on deuterium. The reaction produces a positron and two neutrons in coincidence. This distinctive signature allows a search with very low background for \nuebar's from the Sun and other potential sources. Both differential and integral limits on the \nuebar flux have been placed in the energy range from 4 -- 14.8 MeV. For an energy-independent \nu_e --> \nuebar conversion mechanism, the integral limit on the flux of solar \nuebar's in the energy range from 4 -- 14.8 MeV is found to be \Phi_\nuebar <= 3.4 x 10^4 cm^{-2} s^{-1} (90% C.L.), which corresponds to 0.81% of the standard solar model 8B \nu_e flux of 5.05 x 10^6 cm^{-2} s^{-1}, and is consistent with the more sensitive limit from KamLAND in the 8.3 -- 14.8 MeV range of 3.7 x 10^2 cm^{-2} s^{-1} (90% C.L.). In the energy range from 4 -- 8 MeV, a search for \nuebar's is conducted using coincidences in which only the two neutrons are detected. Assuming a \nuebar spectrum for the neutron induced fission of naturally occurring elements, a flux limit of Phi_\nuebar <= 2.0 x 10^6 cm^{-2} s^{-1}(90% C.L.) is obtained.Comment: submitted to Phys. Rev.

    Meta-analysis of binary outcomes via generalized linear mixed models: a simulation study

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    Background: Systematic reviews and meta-analyses of binary outcomes are widespread in all areas of application. The odds ratio, in particular, is by far the most popular effect measure. However, the standard meta-analysis of odds ratios using a random-effects model has a number of potential problems. An attractive alternative approach for the meta-analysis of binary outcomes uses a class of generalized linear mixed models (GLMMs). GLMMs are believed to overcome the problems of the standard random-effects model because they use a correct binomial-normal likelihood. However, this belief is based on theoretical considerations, and no sufficient simulations have assessed the performance of GLMMs in meta-analysis. This gap may be due to the computational complexity of these models and the resulting considerable time requirements. Methods: The present study is the first to provide extensive simulations on the performance of four GLMM methods (models with fixed and random study effects and two conditional methods) for meta-analysis of odds ratios in comparison to the standard random effects model. Results: In our simulations, the hypergeometric-normal model provided less biased estimation of the heterogeneity variance than the standard random-effects meta-analysis using the restricted maximum likelihood (REML) estimation when the data were sparse, but the REML method performed similarly for the point estimation of the odds ratio, and better for the interval estimation. Conclusions: It is difficult to recommend the use of GLMMs in the practice of meta-analysis. The problem of finding uniformly good methods of the meta-analysis for binary outcomes is still open
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