580 research outputs found

    PHB2 SF-12 Osteoarthritis-Specific Health Index: Development And Validation

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    A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells

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    Viral mutational escape can reduce or abrogate recognition by the T cell receptor (TCR) of virus-specific CD8+ T cells. However, very little is known about the impact of cytotoxic T lymphocyte (CTL) epitope mutations on interactions between peptide–major histocompatibility complex (MHC) class I complexes and MHC class I receptors expressed on other cell types. Here, we analyzed a variant of the immunodominant human leukocyte antigen (HLA)-B2705–restricted HIV-1 Gag KK10 epitope (KRWIILGLNK) with an L to M amino acid substitution at position 6 (L6M), which arises as a CTL escape variant after primary infection but is sufficiently immunogenic to elicit a secondary, de novo HIV-1–specific CD8+ T cell response with an alternative TCR repertoire in chronic infection. In addition to altering recognition by HIV-1–specific CD8+ T cells, the HLA-B2705–KK10 L6M complex also exhibits substantially increased binding to the immunoglobulin-like transcript (ILT) receptor 4, an inhibitory MHC class I–specific receptor expressed on myelomonocytic cells. Binding of the B2705–KK10 L6M complex to ILT4 leads to a tolerogenic phenotype of myelomonocytic cells with lower surface expression of dendritic cell (DC) maturation markers and co-stimulatory molecules. These data suggest a link between CTL-driven mutational escape, altered recognition by innate MHC class I receptors on myelomonocytic cells, and functional impairment of DCs, and thus provide important new insight into biological consequences of viral sequence diversificatio

    Precision on leptonic mixing parameters at future neutrino oscillation experiments

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    We perform a comparison of the different future neutrino oscillation experiments based on the achievable precision in the determination of the fundamental parameters theta_{13} and the CP phase, delta, assuming that theta_{13} is in the range indicated by the recent Daya Bay measurement. We study the non-trivial dependence of the error on delta on its true value. When matter effects are small, the largest error is found at the points where CP violation is maximal, and the smallest at the CP conserving points. The situation is different when matter effects are sizable. As a result of this effect, the comparison of the physics reach of different experiments on the basis of the CP discovery potential, as usually done, can be misleading. We have compared various proposed super-beam, beta-beam and neutrino factory setups on the basis of the relative precision of theta_{13} and the error on delta. Neutrino factories, both high-energy or low-energy, outperform alternative beam technologies. An ultimate precision on theta_{13} below 3% and an error on delta of < 7^{\circ} at 1 sigma (1 d.o.f.) can be obtained at a neutrino factory.Comment: Minor changes, matches version accepted in JHEP. 30 pages, 9 figure

    Probing the Neutrino Mass Hierarchy with Super-Kamiokande

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    We show that for recently discovered large values of theta(13), a superbeam with an average neutrino energy of ~ 5 GeV, such as those being proposed at CERN, if pointing to Super-Kamiokande (L = 8770 km), could reveal the neutrino mass hierarchy at 5 sigma in less than two years irrespective of the true hierarchy and CP phase. The measurement relies on the near resonant matter effect in the numu to nue oscillation channel, and can be done counting the total number of appearance events with just a neutrino beam.Comment: 16 pages, 7 pdf figures, 2 tables. Format changed and text extended. Four new pdf figures added. Dependency of the result on 1-3 mixing angle discussed. Conclusions unchanged. Accepted in JHE

    Blood cultures for the diagnosis of multidrug-resistant and extensively drug-resistant tuberculosis among HIV-infected patients from rural South Africa: a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>The yield of mycobacterial blood cultures for multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) among drug-resistant TB suspects has not been described.</p> <p>Methods</p> <p>We performed a retrospective, cross-sectional analysis to determine the yield of mycobacterial blood cultures for MDR-TB and XDR-TB among patients suspected of drug-resistant TB from rural South Africa. Secondary outcomes included risk factors of <it>Mycobacterium tuberculosis </it>bacteremia and the additive yield of mycobacterial blood cultures compared to sputum culture.</p> <p>Results</p> <p>From 9/1/2006 to 12/31/2008, 130 patients suspected of drug-resistant TB were evaluated with mycobacterial blood culture. Each patient had a single mycobacterial blood culture with 41 (32%) positive for <it>M. tuberculosis</it>, of which 20 (49%) were XDR-TB and 8 (20%) were MDR-TB. One hundred fourteen (88%) patients were known to be HIV-infected. Patients on antiretroviral therapy were significantly less likely to have a positive blood culture for <it>M. tuberculosis </it>(p = 0.002). The diagnosis of MDR or XDR-TB was made by blood culture alone in 12 patients.</p> <p>Conclusions</p> <p>Mycobacterial blood cultures provided an additive yield for diagnosis of drug-resistant TB in patients with HIV from rural South Africa. The use of mycobacterial blood cultures should be considered in all patients suspected of drug-resistant TB in similar settings.</p

    Alteration of the phospho- or neutral lipid content and fatty acid composition in Listeria monocytogenes due to acid adaptation mechanisms for hydrochloric, acetic and lactic acids at pH 5.5 or benzoic acid at neutral pH

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    This study provides a first approach to observe the effects on Listeria monocytogenes of cellular exposure to acid stress at low or neutral pH, notably how phospho- or neutral lipids are involved in this mechanism, besides the fatty acid profile alteration. A thorough investigation of the composition of polar and neutral lipids from L. monocytogenes grown at pH 5.5 in presence of hydrochloric, acetic and lactic acids, or at neutral pH 7.3 in presence of benzoic acid, is described relative to cells grown in acid-free medium. The results showed that only low pH values enhance the antimicrobial activity of an acid. We suggest that, irrespective of pH, the acid adaptation response will lead to a similar alteration in fatty acid composition [decreasing the ratio of branched chain/saturated straight fatty acids of total lipids], mainly originating from the neutral lipid class of adapted cultures. Acid adaptation in L. monocytogenes was correlated with a decrease in total lipid phosphorus and, with the exception of cells adapted to benzoic acid, this change in the amount of phosphorus reflected a higher content of the neutral lipid class. Upon acetic or benzoic acid stress the lipid phosphorus proportion was analysed in the main phospholipids present: cardiolipin, phosphatidylglycerol, phosphoaminolipid and phosphatidylinositol. Interestingly only benzoic acid had a dramatic effect on the relative quantities of these four phospholipids

    Soft branes in supersymmetry-breaking backgrounds

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    We revisit the analysis of effective field theories resulting from non-supersymmetric perturbations to supersymmetric flux compactifications of the type-IIB superstring with an eye towards those resulting from the backreaction of a small number of anti-D3-branes. Independently of the background, we show that the low-energy Lagrangian describing the fluctuations of a stack of probe D3-branes exhibits soft supersymmetry breaking, despite perturbations to marginal operators that were not fully considered in some previous treatments. We take this as an indication that the breaking of supersymmetry by anti-D3-branes or other sources may be spontaneous rather than explicit. In support of this, we consider the action of an anti-D3-brane probing an otherwise supersymmetric configuration and identify a candidate for the corresponding goldstino.Comment: 36+5 pages. References added, minor typos correcte

    Reuse of structural domain–domain interactions in protein networks

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    <p>Abstract</p> <p>Background</p> <p>Protein interactions are thought to be largely mediated by interactions between structural domains. Databases such as <it>i</it>Pfam relate interactions in protein structures to known domain families. Here, we investigate how the domain interactions from the <it>i</it>Pfam database are distributed in protein interactions taken from the HPRD, MPact, BioGRID, DIP and IntAct databases.</p> <p>Results</p> <p>We find that known structural domain interactions can only explain a subset of 4–19% of the available protein interactions, nevertheless this fraction is still significantly bigger than expected by chance. There is a correlation between the frequency of a domain interaction and the connectivity of the proteins it occurs in. Furthermore, a large proportion of protein interactions can be attributed to a small number of domain interactions. We conclude that many, but not all, domain interactions constitute reusable modules of molecular recognition. A substantial proportion of domain interactions are conserved between <it>E. coli</it>, <it>S. cerevisiae </it>and <it>H. sapiens</it>. These domains are related to essential cellular functions, suggesting that many domain interactions were already present in the last universal common ancestor.</p> <p>Conclusion</p> <p>Our results support the concept of domain interactions as reusable, conserved building blocks of protein interactions, but also highlight the limitations currently imposed by the small number of available protein structures.</p
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