747 research outputs found

    HIV-1 Vpr Enhances Viral Burden by Facilitating Infection of Tissue Macrophages but Not Nondividing CD4+ T Cells

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    Prior experiments in explants of human lymphoid tissue have demonstrated that human immunodeficiency virus type 1 (HIV-1) productively infects diverse cellular targets including T cells and tissue macrophages. We sought to determine the specific contribution of macrophages and T cells to the overall viral burden within lymphoid tissue. To block infection of macrophages selectively while preserving infection of T cells, we used viruses deficient for viral protein R (Vpr) that exhibit profound replication defects in nondividing cells in vitro. We inoculated tonsil histocultures with matched pairs of congenic viruses that differed only by the presence of a wild-type or truncated vpr gene. Although these viruses exhibited no reduction in the infection or depletion of T cells, the ability of the Vpr-deficient R5 virus to infect tissue macrophages was severely impaired compared with matched wild-type R5 virus. Interestingly, the Vpr-deficient R5 virus also exhibited a 50% reduction in overall virus replication compared with its wild-type counterpart despite the fact that macrophages represent a small fraction of the potential targets of HIV-1 infection in these tissues. Collectively, these data highlight the importance of tissue macrophages in local viral burden and further implicate roles for CC chemokine receptor 5, macrophages, and Vpr in the life cycle and pathogenesis of HIV-1

    Extrapolating SMBH correlations down the mass scale: the case for IMBHs in globular clusters

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    Empirical evidence for both stellar mass black holes M_bh<10^2 M_sun) and supermassive black holes (SMBHs, M_bh>10^5 M_sun) is well established. Moreover, every galaxy with a bulge appears to host a SMBH, whose mass is correlated with the bulge mass, and even more strongly with the central stellar velocity dispersion sigma_c, the `M-sigma' relation. On the other hand, evidence for "intermediate-mass" black holes (IMBHs, with masses in the range 1^2 - 10^5 M_sun) is relatively sparse, with only a few mass measurements reported in globular clusters (GCs), dwarf galaxies and low-mass AGNs. We explore the question of whether globular clusters extend the M-sigma relationship for galaxies to lower black hole masses and find that available data for globular clusters are consistent with the extrapolation of this relationship. We use this extrapolated M-sigma relationship to predict the putative black hole masses of those globular clusters where existence of central IMBH was proposed. We discuss how globular clusters can be used as a constraint on theories making specific predictions for the low-mass end of the M-sigma relation.Comment: 14 pages, 3 figures, accepted for publication in Astrophysics and Space Science; fixed typos and a quote in Sec.

    Observed photodetachment in parallel electric and magnetic fields

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    We investigate photodetachment from negative ions in a homogeneous 1.0-T magnetic field and a parallel electric field of approximately 10 V/cm. A theoretical model for detachment in combined fields is presented. Calculations show that a field of 10 V/cm or more should considerably diminish the Landau structure in the detachment cross section. The ions are produced and stored in a Penning ion trap and illuminated by a single-mode dye laser. We present preliminary results for detachment from S- showing qualitative agreement with the model. Future directions of the work are also discussed.Comment: Nine pages, five figures, minor revisions showing final publicatio

    Non-minimally Coupled Tachyonic Inflation in Warped String Background

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    We show that the non-minimal coupling of tachyon field to the scalar curvature, as proposed by Piao et al, with the chosen coupling parameter does not produce the effective potential where the tachyon field can roll down from T=0 to large TT along the slope of the potential. We find a correct choice of the parameters which ensures this requirement and support slow-roll inflation. However, we find that the cosmological parameter found from the analysis of the theory are not in the range obtained from observations. We then invoke warped compactification and varying dilaton field over the compact manifold, as proposed by Raeymaekers, to show that in such a setup the observed parameter space can be ensured.Comment: minor typos corrected and references adde

    Psychometric performance of the perceived stigma of substance abuse scale (PSAS) among patients on methadone maintenance therapy in Vietnam

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    Background: People who inject drugs (PWID) and patients on methadone maintenance therapy (MMT) face severe stigma and discrimination. However, there are limited measures assessing stigma towards individuals with substance use disorders or MMT patients, particularly in Vietnam, and few studies have examined the psychometric properties of existing measures. This study aims to examine the performance of the eight-item Perceived Stigma of Substance Abuse Scale (PSAS), created in the United States, among a population of MMT patients in Vietnam. Methods: A cross-sectional survey was conducted among 400 adult patients enrolled in an urban MMT clinic. Substance use stigma was measured using the PSAS. We conducted confirmatory factor analysis (CFA) and assessed construct validity, reliability and known-group validity. Results: The original eight-item scale was unidimensional, but yielded mixed goodness-of-fit indicators. Ultimately, dropping two items and allowing the errors of the items related to childcare to correlate improved the goodness-of-fit indicators. (RMSEA = 0.025; CFI = 0.999; and SRMR = 0.018). The shortened scale demonstrated acceptable reliability (Cronbach's α = 0.766). The mean stigma scores were significantly higher among individuals not working, but did not significantly vary by length of time in MMT, marital status, education attainment, HIV status, depression, concurrent injection drug use or missed methadone dose. Conclusions: The shortened six-item scale demonstrated good construct validity and acceptability reliability, but it did not demonstrate many a priori hypothesized known-group validity associations. Further research should consider a mixed-methods validation approach

    Finding Faint Intermediate-mass Black Holes in the Radio Band

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    We discuss the prospects for detecting faint intermediate-mass black holes, such as those predicted to exist in the cores of globular clusters and dwarf spheroidal galaxies. We briefly summarize the difficulties of stellar dynamical searches, then show that recently discovered relations between black hole mass, X-ray luminosity and radio luminosity imply that in most cases, these black holes should be more easily detected in the radio than in the X-rays. Finally, we show upper limits from some radio observations of globular clusters, and discuss the possibility that the radio source in the core of the Ursa Minor dwarf spheroidal galaxy might be a 10,000100,000M\sim 10,000-100,000 M_\odot black hole.Comment: 10 pages, no figures, to appear in From X-ray Binaries to Quasars: Black Hole Accretion on All Mass Scales, ed. T. J. Maccarone, R. P. Fender, and L. C. Ho (Dordrecht: Kluwer

    Resonance- and Chaos-Assisted Tunneling

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    We consider dynamical tunneling between two symmetry-related regular islands that are separated in phase space by a chaotic sea. Such tunneling processes are dominantly governed by nonlinear resonances, which induce a coupling mechanism between ``regular'' quantum states within and ``chaotic'' states outside the islands. By means of a random matrix ansatz for the chaotic part of the Hamiltonian, one can show that the corresponding coupling matrix element directly determines the level splitting between the symmetric and the antisymmetric eigenstates of the pair of islands. We show in detail how this matrix element can be expressed in terms of elementary classical quantities that are associated with the resonance. The validity of this theory is demonstrated with the kicked Harper model.Comment: 25 pages, 5 figure

    Use of high-frequency ultrasound to study the prenatal development of cranial neural tube defects and hydrocephalus in Gldc-deficient mice

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    Objective: We used non-invasive high-frequency ultrasound (HFUS) imaging to investigate embryonic brain development in a mouse model for neural tube defects (NTDs) and non-ketotic hyperglycinemia (NKH). Method: Using HFUS, we imaged embryos carrying loss of function alleles of Gldc encoding glycine decarboxylase, a component of the glycine cleavage system in mitochondrial folate metabolism, which is known to be associated with cranial NTDs and NKH in humans. We serially examined the same litter during the second half of embryonic development and quantified cerebral structures. Genotype was confirmed using PCR. Histology was used to confirm ultrasound findings. Results: High-frequency ultrasound allowed in utero detection of two major brain abnormalities in Gldc-deficient mouse embryos, cranial NTDs (exencephaly) and ventriculomegaly (corresponding with the previous finding of post-natal hydrocephalus). Serial ultrasound allowed individual embryos to be analysed at successive gestational time points. From embryonic day 16.5 to 18.5, the lateral ventricle volume reduced in wild-type and heterozygous embryos but increased in homozygous Gldc-deficient embryos. Conclusion: Exencephaly and ventriculomegaly were detectable by HFUS in homozygous Gldc-deficient mouse embryos indicating this to be an effective tool to study CNS development. Longitudinal analysis of the same embryo allowed the prenatal onset and progression of ventricle enlargement in Gldc-deficient mice to be determined
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