1,231 research outputs found

    Hypermoduli Stabilization, Flux Attractors, and Generating Functions

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    We study stabilization of hypermoduli with emphasis on the effects of generalized fluxes. We find a class of no-scale vacua described by ISD conditions even in the presence of geometric flux. The associated flux attractor equations can be integrated by a generating function with the property that the hypermoduli are determined by a simple extremization principle. We work out several orbifold examples where all vector moduli and many hypermoduli are stabilized, with VEVs given explicitly in terms of fluxes.Comment: 45 pages, no figures; Version submitted to JHE

    Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

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    Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

    Accuracy of five algorithms to diagnose gambiense human African trypanosomiasis.

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    Algorithms to diagnose gambiense human African trypanosomiasis (HAT, sleeping sickness) are often complex due to the unsatisfactory sensitivity and/or specificity of available tests, and typically include a screening (serological), confirmation (parasitological) and staging component. There is insufficient evidence on the relative accuracy of these algorithms. This paper presents estimates of the accuracy of five algorithms used by past Médecins Sans Frontières programmes in the Republic of Congo, Southern Sudan and Uganda

    <i>Trypanosoma brucei rhodesiense</i> transmitted by a single tsetse fly bite in vervet monkeys as a model of human African trypanosomiasis

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    Sleeping sickness is caused by a species of trypanosome blood parasite that is transmitted by tsetse flies. To understand better how infection with this parasite leads to disease, we provide here the most detailed description yet of the course of infection and disease onset in vervet monkeys. One infected tsetse fly was allowed to feed on each host individual, and in all cases infections were successful. The characteristics of infection and disease were similar in all hosts, but the rate of progression varied considerably. Parasites were first detected in the blood 4-10 days after infection, showing that migration of parasites from the site of fly bite was very rapid. Anaemia was a key feature of disease, with a reduction in the numbers and average size of red blood cells and associated decline in numbers of platelets and white blood cells. One to six weeks after infection, parasites were observed in the cerebrospinal fluid (CSF), indicating that they had moved from the blood into the brain; this was associated with a white cell infiltration. This study shows that fly-transmitted infection in vervets accurately mimics human disease and provides a robust model to understand better how sleeping sickness develops

    F-Theory and the Mordell-Weil Group of Elliptically-Fibered Calabi-Yau Threefolds

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    The Mordell-Weil group of an elliptically fibered Calabi-Yau threefold X contains information about the abelian sector of the six-dimensional theory obtained by compactifying F-theory on X. After examining features of the abelian anomaly coefficient matrix and U(1) charge quantization conditions of general F-theory vacua, we study Calabi-Yau threefolds with Mordell-Weil rank-one as a first step towards understanding the features of the Mordell-Weil group of threefolds in more detail. In particular, we generate an interesting class of F-theory models with U(1) gauge symmetry that have matter with both charges 1 and 2. The anomaly equations --- which relate the Neron-Tate height of a section to intersection numbers between the section and fibral rational curves of the manifold --- serve as an important tool in our analysis.Comment: 29 pages + appendices, 5 figures; v2: minor correction

    Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

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    To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

    Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

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    CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

    Scalar geometry and masses in Calabi-Yau string models

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    We study the geometry of the scalar manifolds emerging in the no-scale sector of Kahler moduli and matter fields in generic Calabi-Yau string compactifications, and describe its implications on scalar masses. We consider both heterotic and orientifold models and compare their characteristics. We start from a general formula for the Kahler potential as a function of the topological compactification data and study the structure of the curvature tensor. We then determine the conditions for the space to be symmetric and show that whenever this is the case the heterotic and the orientifold models give the same scalar manifold. We finally study the structure of scalar masses in this type of geometries, assuming that a generic superpotential triggers spontaneous supersymmetry breaking. We show in particular that their behavior crucially depends on the parameters controlling the departure of the geometry from the coset situation. We first investigate the average sGoldstino mass in the hidden sector and its sign, and study the implications on vacuum metastability and the mass of the lightest scalar. We next examine the soft scalar masses in the visible sector and their flavor structure, and study the possibility of realizing a mild form of sequestering relying on a global symmetry.Comment: 36 pages, no figure
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