1,267 research outputs found

    Charged Scalar-Tensor Boson Stars: Equilibrium, Stability and Evolution

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    We study charged boson stars in scalar-tensor (ST) gravitational theories. We analyse the weak field limit of the solutions and analytically show that there is a maximum charge to mass ratio for the bosons above which the weak field solutions are not stable. This charge limit can be greater than the GR limit for a wide class of ST theories. We numerically investigate strong field solutions in both the Brans Dicke and power law ST theories. We find that the charge limit decreases with increasing central boson density. We discuss the gravitational evolution of charged and uncharged boson stars in a cosmological setting and show how, at any point in its evolution, the physical properties of the star may be calculated by a rescaling of a solution whose asymptotic value of the scalar field is equal to its initial asymptotic value. We focus on evolution in which the particle number of the star is conserved and we find that the energy and central density of the star decreases as the cosmological time increases. We also analyse the appearance of the scalarization phenomenon recently discovered for neutron stars configurations and, finally, we give a short discussion on how making the correct choice of mass influences the argument over which conformal frame, the Einstein frame or the Jordan frame, is physical.Comment: RevTeX, 27 pages, 9 postscript figures. Minor revisions and updated references. Accepted for publication in Phys. Rev.

    New approaches to measuring anthelminthic drug efficacy: parasitological responses of childhood schistosome infections to treatment with praziquantel

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    By 2020, the global health community aims to control and eliminate human helminthiases, including schistosomiasis in selected African countries, principally by preventive chemotherapy (PCT) through mass drug administration (MDA) of anthelminthics. Quantitative monitoring of anthelminthic responses is crucial for promptly detecting changes in efficacy, potentially indicative of emerging drug resistance. Statistical models offer a powerful means to delineate and compare efficacy among individuals, among groups of individuals and among populations.; We illustrate a variety of statistical frameworks that offer different levels of inference by analysing data from nine previous studies on egg counts collected from African children before and after administration of praziquantel.; We quantify responses to praziquantel as egg reduction rates (ERRs), using different frameworks to estimate ERRs among population strata, as average responses, and within strata, as individual responses. We compare our model-based average ERRs to corresponding model-free estimates, using as reference the World Health Organization (WHO) 90 % threshold of optimal efficacy. We estimate distributions of individual responses and summarize the variation among these responses as the fraction of ERRs falling below the WHO threshold.; Generic models for evaluating responses to anthelminthics deepen our understanding of variation among populations, sub-populations and individuals. We discuss the future application of statistical modelling approaches for monitoring and evaluation of PCT programmes targeting human helminthiases in the context of the WHO 2020 control and elimination goals

    The atmospheric parameters and spectral interpolator for the stars of MILES

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    Context. Empirical libraries of stellar spectra are used for stellar classification and synthesis of stellar populations. MILES is a medium spectral-resolution library in the optical domain covering a wide range of temperatures, surface gravities and metallicities. Aims. We re-determine the atmospheric parameters of these stars in order to improve the homogeneity and accuracy. We build an interpolating function that returns a spectrum as a function of the three atmospheric parameters, and finally, we characterize the precision of the wavelength calibration and stability of the spectral resolution. Methods. We use the ULySS program with the ELODIE library as a reference and compare the results with literature compilations. Results. We obtain precisions of 60 K, 0.13 and 0.05 dex respectively for Teff, log g and [Fe/H] for the FGK stars. For the M stars, the mean errors are 38 K, 0.26 and 0.12 dex, and for the OBA 3.5%, 0.17 and 0.13 dex. We construct an interpolator that we test against the MILES stars themselves. We test it also by measuring the atmospheric parameters of the CFLIB stars with MILES as reference and find it to be more reliable than the ELODIE interpolator for the evolved hot stars, like in particular those of the blue horizontal branch.Comment: A&A accepted, 29 pages, 6 figure

    Multiple molecular mechanisms form a positive feedback loop driving amyloid β42 peptide-induced neurotoxicity via activation of the TRPM2 channel in hippocampal neurons

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    Emerging evidence supports an important role for the ROS-sensitive TRPM2 channel in mediating age-related cognitive impairment in Alzheimer’s disease (AD), particularly neurotoxicity resulting from generation of excessive neurotoxic Aβ peptides. Here we examined the elusive mechanisms by which Aβ₄₂ activates the TRPM2 channel to induce neurotoxicity in mouse hippocampal neurons. Aβ₄₂-induced neurotoxicity was ablated by genetic knockout (TRPM2-KO) and attenuated by inhibition of the TRPM2 channel activity or activation through PARP-1. Aβ₄₂-induced neurotoxicity was also inhibited by treatment with TPEN used as a Zn²⁺-specific chelator. Cell imaging revealed that Aβ₄₂-induced lysosomal dysfunction, cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS. These effects were suppressed by TRPM2-KO, inhibition of TRPM2 or PARP-1, or treatment with TPEN. Bafilomycin-induced lysosomal dysfunction also resulted in TRPM2-dependent cytosolic Zn²⁺ increase, mitochondrial Zn²⁺ accumulation, and mitochondrial generation of ROS, supporting that lysosomal dysfunction and accompanying Zn²⁺ release trigger mitochondrial Zn²⁺ accumulation and generation of ROS. Aβ₄₂-induced effects on lysosomal and mitochondrial functions besides neurotoxicity were also suppressed by inhibition of PKC and NOX. Furthermore, Aβ₄₂-induced neurotoxicity was prevented by inhibition of MEK/ERK. Therefore, our study reveals multiple molecular mechanisms, including PKC/NOX-mediated generation of ROS, activation of MEK/ERK and PARP-1, lysosomal dysfunction and Zn²⁺ release, mitochondrial Zn²⁺ accumulation, loss of mitochondrial function, and mitochondrial generation of ROS, are critically engaged in forming a positive feedback loop that drives Aβ₄₂-induced activation of the TRPM2 channel and neurotoxicity in hippocampal neurons. These findings shed novel and mechanistic insights into AD pathogenesis

    Behavioral origin of sound-evoked activity in mouse visual cortex

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    Sensory cortices can be affected by stimuli of multiple modalities and are thus increasingly thought to be multisensory. For instance, primary visual cortex (V1) is influenced not only by images but also by sounds. Here we show that the activity evoked by sounds in V1, measured with Neuropixels probes, is stereotyped across neurons and even across mice. It is independent of projections from auditory cortex and resembles activity evoked in the hippocampal formation, which receives little direct auditory input. Its low-dimensional nature starkly contrasts the high-dimensional code that V1 uses to represent images. Furthermore, this sound-evoked activity can be precisely predicted by small body movements that are elicited by each sound and are stereotyped across trials and mice. Thus, neural activity that is apparently multisensory may simply arise from low-dimensional signals associated with internal state and behavior

    Phenotyping and diversity assessment of Dendrobium species by using DUS guidelines

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    Dendrobiums are sympodial epiphytic orchids belonging to the family Orchidaceae. and have an extraordinary variation in bloom shape, size and colour. They are widely recognized for their enchanting beauty and longlasting quality. Morphological characterization of Dendrobium species was carried out using the DUS guidelines developed by the Protection of Plant Varieties and Farmers Rights Authority (PPV and FRA) in New Delhi. A total of 15 Dendrobium species were characterized for 52 vegetative and floral traits. Among the 52 traits, 8 were monomorphic, 12 were dimorphic and 32 were polymorphic, indicating their potential for characterization. Principal component analysis showed 86.14% variation in the first 4 principal components with an eigenvalue >1.0. The first and second principal components explained 41.43% and 19.45% of the total variation respectively. The dendrogram produced by a Ward analysis validated the Principal Component Analysis (PCA) findings. The Dendrobium species were grouped into 2 major clusters with three sub-clusters based on the correlation between the morphological traits among the species. Characterization established distinctiveness amongst the Dendrobium species. Breeders/farmers can use this study to distinguish between different species and apply for protection through the PPV and FR Authority, New Delhi. The trait-specific data generated while characterizing can be used to develop new inter-specific hybrids, which are common in orchids

    Relationship between Antibody Susceptibility and Lipopolysaccharide O-Antigen Characteristics of Invasive and Gastrointestinal Nontyphoidal Salmonellae Isolates from Kenya

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    Background: Nontyphoidal Salmonellae (NTS) cause a large burden of invasive and gastrointestinal disease among young children in sub-Saharan Africa. No vaccine is currently available. Previous reports indicate the importance of the O-antigen of Salmonella lipopolysaccharide for virulence and resistance to antibody-mediated killing. We hypothesised that isolates with more O-antigen have increased resistance to antibody-mediated killing and are more likely to be invasive than gastrointestinal. Methodology/Principal findings: We studied 192 NTS isolates (114 Typhimurium, 78 Enteritidis) from blood and stools, mostly from paediatric admissions in Kenya 2000-2011. Isolates were tested for susceptibility to antibody-mediated killing, using whole adult serum. O-antigen structural characteristics, including O-acetylation and glucosylation, were investigated. Overall, isolates were susceptible to antibody-mediated killing, but S. Enteritidis were less susceptible and expressed more O-antigen than Typhimurium (p\u3c0.0001 for both comparisons). For S. Typhimurium, but not Enteritidis, O-antigen expression correlated with reduced sensitivity to killing (r = 0.29, 95% CI = 0.10-0.45, p = 0.002). Both serovars expressed O-antigen populations ranging 21-33 kDa average molecular weight. O-antigen from most Typhimurium were O-acetylated on rhamnose and abequose residues, while Enteritidis O-antigen had low or no O-acetylation. Both Typhimurium and Enteritidis O-antigen were approximately 20%-50% glucosylated. Amount of S. Typhimurium O-antigen and O-antigen glucosylation level were inversely related. There was no clear association between clinical presentation and antibody susceptibility, O-antigen level or other O-antigen features. Conclusion/Significance: Kenyan S. Typhimurium and Enteritidis clinical isolates are susceptible to antibody-mediated killing, with degree of susceptibility varying with level of O-antigen for S. Typhimurium. This supports the development of an antibody-inducing vaccine against NTS for Africa. No clear differences were found in the phenotype of isolates from blood and stool, suggesting that the same isolates can cause invasive disease and gastroenteritis. Genome studies are required to understand whether invasive and gastrointestinal isolates differ at the genotypic level

    Amyloid precursor protein drives down-regulation of mitochondrial oxidative phosphorylation independent of amyloid beta

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    Amyloid precursor protein (APP) and its extracellular domain, soluble APP alpha (sAPPα) play important physiological and neuroprotective roles. However, rare forms of familial Alzheimer’s disease are associated with mutations in APP that increase toxic amyloidogenic cleavage of APP and produce amyloid beta (Aβ) at the expense of sAPPα and other non-amyloidogenic fragments. Although mitochondrial dysfunction has become an established hallmark of neurotoxicity, the link between Aβ and mitochondrial function is unclear. In this study we investigated the effects of increased levels of neuronal APP or Aβ on mitochondrial metabolism and gene expression, in human SH-SY5Y neuroblastoma cells. Increased non-amyloidogenic processing of APP, but not Aβ, profoundly decreased respiration and enhanced glycolysis, while mitochondrial DNA (mtDNA) transcripts were decreased, without detrimental effects to cell growth. These effects cannot be ascribed to Aβ toxicity, since higher levels of endogenous Aβ in our models do not cause oxidative phosphorylation (OXPHOS) perturbations. Similarly, chemical inhibition of β-secretase decreased mitochondrial respiration, suggesting that non-amyloidogenic processing of APP may be responsible for mitochondrial changes. Our results have two important implications, the need for caution in the interpretation of mitochondrial perturbations in models where APP is overexpressed, and a potential role of sAPPα or other non-amyloid APP fragments as acute modulators of mitochondrial metabolism

    How hybrids manage growth and social–business tensions in global supply chains: the case of impact sourcing

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    This study contributes to the growing interest in how hybrid organizations manage paradoxical social–business tensions. Our empirical case is ‘‘impact sourcing’’— hybrids in global supply chains that hire staff from disadvantaged communities to provide services to business clients. We identify two major growth orientations— ‘‘community-focused’’ and ‘‘client-focused’’ growth—their inherent tensions and ways that hybrids manage them. The former favors slow growth and manages tensions through highly integrated client and community relations; the latter promotes faster growth and manages client and community relations separately. Both growth orientations address social–business tensions in particular ways, but also create latent constraints that manifest when entrepreneurial aspirations conflict with the current growth path. In presenting and discussing our findings, we introduce preempting management practices of tensions, and the importance of geographic embeddedness and distance to the paradox literature
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