6,090 research outputs found

    The mass distribution of the Fornax dSph: constraints from its globular cluster distribution

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    Uniquely among the dwarf spheroidal (dSph) satellite galaxies of the Milky Way, Fornax hosts globular clusters. It remains a puzzle as to why dynamical friction has not yet dragged any of Fornax's five globular clusters to the centre, and also why there is no evidence that any similar star cluster has been in the past (for Fornax or any other dSph). We set up a suite of 2800 N-body simulations that sample the full range of globular-cluster orbits and mass models consistent with all existing observational constraints for Fornax. In agreement with previous work, we find that if Fornax has a large dark-matter core then its globular clusters remain close to their currently observed locations for long times. Furthermore, we find previously unreported behaviour for clusters that start inside the core region. These are pushed out of the core and gain orbital energy, a process we call 'dynamical buoyancy'. Thus a cored mass distribution in Fornax will naturally lead to a shell-like globular cluster distribution near the core radius, independent of the initial conditions. By contrast, CDM-type cusped mass distributions lead to the rapid infall of at least one cluster within \Delta t = 1-2Gyr, except when picking unlikely initial conditions for the cluster orbits (\sim 2% probability), and almost all clusters within \Delta t = 10Gyr. Alternatively, if Fornax has only a weakly cusped mass distribution, dynamical friction is much reduced. While over \Delta t = 10Gyr this still leads to the infall of 1-4 clusters from their present orbits, the infall of any cluster within \Delta t = 1-2Gyr is much less likely (with probability 0-70%, depending on \Delta t and the strength of the cusp). Such a solution to the timing problem requires that in the past the globular clusters were somewhat further from Fornax than today; they most likely did not form within Fornax, but were accreted.Comment: 12 pages, 8 figures, 3 tables, submitted to MNRA

    The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

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    Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

    The CSF immune response in HIV-1-associated cryptococcal meningitis: macrophage activation, correlates of disease severity and effect of antiretroviral therapy.

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    Immune modulation may improve outcome in HIV-associated cryptococcal meningitis. Animal studies suggest alternatively activated macrophages are detrimental but human studies are limited. We performed a detailed assessment of the cerebrospinal fluid (CSF) immune response and examined immune correlates of disease severity and poor outcome, and the effects of antiretroviral therapy (ART). We enrolled persons ≥18 years with first episode of HIV-associated cryptococcal meningitis. CSF immune response was assessed using flow cytometry and multiplex cytokine analysis. Principal component analysis was used to examine relationships between immune response, fungal burden, intracranial pressure and mortality, and the effects of recent ART initiation (<12 weeks). CSF was available from 57 persons (median CD4 34/μL). CD206 (alternatively activated macrophage marker) was expressed on 54% CD14+ and 35% CD14- monocyte-macrophages. High fungal burden was not associated with CD206 expression but with a paucity of CD4+, CD8+ and CD4-CD8- T cells and lower IL-6, G-CSF and IL-5 concentrations. High intracranial pressure (≥30cmH2O) was associated with fewer T cells, a higher fungal burden and larger Cryptococcus organisms. Mortality was associated with reduced interferon-gamma concentrations and CD4-CD8- T cells but lost statistical significance when adjusted for multiple comparisons. Recent ART was associated with increased CSF CD4/CD8 ratio and a significantly increased macrophage expression of CD206. Paucity of CSF T cell infiltrate rather than alternative macrophage activation was associated with severe disease in HIV-associated cryptococcosis. ART had a pronounced effect on the immune response at the site of disease

    Regularly log-periodic functions and some applications

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    We prove a Tauberian theorem for the Laplace--Stieltjes transform and Karamata-type theorems in the framework of regularly log-periodic functions. As an application we determine the exact tail behavior of fixed points of certain type smoothing transforms

    Three-Year Follow-Up of Participants from a Self-Weighing Randomized Controlled Trial

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    Frequent self-weighing is associated with weight loss maintenance. Several years ago, we investigated frequent self-weighing’s effect on weight loss and found the participants lost a significant amount of weight. Three years after this trial's end, participants were contacted for an update on their weight and self-weighing frequency. Weight change and self-weighing frequency since the end of the study were assessed. We hypothesized that participants who maintained frequent self-weighing behavior would have maintained their weight loss. Out of 98 participants enrolled in the RCT, 37% (n = 36) participated in this follow-up study. Total weight loss during the trial for the follow-up participants was 12.7 ± 19.4 lbs (p<0.001). Three years after intervention, participants regained 0.9 ± 4.34 lbs, a value that was not statistically different from zero (p=0.75). This did not differ by gender (p=0.655). Over 75% of these participants continued to weigh themselves at least once a week. Frequent self-weighing may be an effective, low-cost strategy for weight loss maintenance. Future research should further investigate the role of self-weighing in long-term weight gain prevention

    Coherent frequentism

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    By representing the range of fair betting odds according to a pair of confidence set estimators, dual probability measures on parameter space called frequentist posteriors secure the coherence of subjective inference without any prior distribution. The closure of the set of expected losses corresponding to the dual frequentist posteriors constrains decisions without arbitrarily forcing optimization under all circumstances. This decision theory reduces to those that maximize expected utility when the pair of frequentist posteriors is induced by an exact or approximate confidence set estimator or when an automatic reduction rule is applied to the pair. In such cases, the resulting frequentist posterior is coherent in the sense that, as a probability distribution of the parameter of interest, it satisfies the axioms of the decision-theoretic and logic-theoretic systems typically cited in support of the Bayesian posterior. Unlike the p-value, the confidence level of an interval hypothesis derived from such a measure is suitable as an estimator of the indicator of hypothesis truth since it converges in sample-space probability to 1 if the hypothesis is true or to 0 otherwise under general conditions.Comment: The confidence-measure theory of inference and decision is explicitly extended to vector parameters of interest. The derivation of upper and lower confidence levels from valid and nonconservative set estimators is formalize

    Flow cytometry to assess CSF fungal burden in cryptococcal meningitis

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    Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis but its use to aid clinical decision-making is hampered by the time involved to perform quantitative cultures. Here we demonstrate the potential of flow cytometry as a novel and rapid technique to address this
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