5,616 research outputs found

    Two problems related to prescribed curvature measures

    Full text link
    Existence of convex body with prescribed generalized curvature measures is discussed, this result is obtained by making use of Guan-Li-Li's innovative techniques. In surprise, that methods has also brought us to promote Ivochkina's C2C^2 estimates for prescribed curvature equation in \cite{I1, I}.Comment: 12 pages, Corrected typo

    NFU-Enabled FASTA: moving bioinformatics applications onto wide area networks

    Get PDF
    Abstract Background Advances in Internet technologies have allowed life science researchers to reach beyond the lab-centric research paradigm to create distributed collaborations. Of the existing technologies that support distributed collaborations, there are currently none that simultaneously support data storage and computation as a shared network resource, enabling computational burden to be wholly removed from participating clients. Software using computation-enable logistical networking components of the Internet Backplane Protocol provides a suitable means to accomplish these tasks. Here, we demonstrate software that enables this approach by distributing both the FASTA algorithm and appropriate data sets within the framework of a wide area network. Results For large datasets, computation-enabled logistical networks provide a significant reduction in FASTA algorithm running time over local and non-distributed logistical networking frameworks. We also find that genome-scale sizes of the stored data are easily adaptable to logistical networks. Conclusion Network function unit-enabled Internet Backplane Protocol effectively distributes FASTA algorithm computation over large data sets stored within the scaleable network. In situations where computation is subject to parallel solution over very large data sets, this approach provides a means to allow distributed collaborators access to a shared storage resource capable of storing the large volumes of data equated with modern life science. In addition, it provides a computation framework that removes the burden of computation from the client and places it within the network

    Human Infection with Highly Pathogenic Avian Influenza A(H7N9) Virus, China

    Get PDF
    The recent increase in zoonotic avian influenza A(H7N9) disease in China is a cause of public health concern. Most of the A(H7N9) viruses previously reported have been of low pathogenicity. We report the fatal case of a patient in China who was infected with an A(H7N9) virus having a polybasic amino acid sequence at its hemagglutinin cleavage site (PEVPKRKRTAR/GL), a sequence suggestive of high pathogenicity in birds. Its neuraminidase also had R292K, an amino acid change known to be associated with neuraminidase inhibitor resistance. Both of these molecular features might have contributed to the patient's adverse clinical outcome. The patient had a history of exposure to sick and dying poultry, and his close contacts had no evidence of A(H7N9) disease, suggesting human-to-human transmission did not occur. Enhanced surveillance is needed to determine whether this highly pathogenic avian influenza A(H7N9) virus will continue to spread.published_or_final_versio

    Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

    Get PDF
    BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC

    Interdependent network reciprocity in evolutionary games

    Get PDF
    Besides the structure of interactions within networks, also the interactions between networks are of the outmost importance. We therefore study the outcome of the public goods game on two interdependent networks that are connected by means of a utility function, which determines how payoffs on both networks jointly influence the success of players in each individual network. We show that an unbiased coupling allows the spontaneous emergence of interdependent network reciprocity, which is capable to maintain healthy levels of public cooperation even in extremely adverse conditions. The mechanism, however, requires simultaneous formation of correlated cooperator clusters on both networks. If this does not emerge or if the coordination process is disturbed, network reciprocity fails, resulting in the total collapse of cooperation. Network interdependence can thus be exploited effectively to promote cooperation past the limits imposed by isolated networks, but only if the coordination between the interdependent networks is not disturbe

    Mutant K-ras oncogene regulates steroidogenesis of normal human adrenocortical cells by the RAF-MEK-MAPK pathway

    Get PDF
    The result of our previous study has shown that the K-ras mutant (pK568MRSV) transfected human adrenocortical cells can significantly increase cortisol production and independently cause cell transformation. The aim of this study is to investigate the effect of the active K-ras oncogene on the cortisol production in normal human adrenocortical cells. First we used isopropyl thiogalactoside to induce the inducible mutant K-ras expression plasmid, pK568MRSV, in the stable transfected human adrenocortical cells. The result showed that the increase of RasGTP levels in transfected cells was time-dependent after isopropyl thiogalactoside induction. Additionally, results from Western blot analysis revealed significant elevation in phosphorylation of c-Raf-1 and Mitogen-activated protein kinase. We also detected the levels of mRNA encoding Cholesterol side-chain cleavage enzyme (P450SCC), 17α-Hydroxylase/17,20-lyase (P450c17) and 3β-Hydroxysteroid dehydrogenase (3βHSD) were increased in human adrenocortical cells transfected with mutant K-ras after IPTG treatment. The increase of mRNA amount in P450scc P450c17 and 3βHSD and the elevation of cortisol level were inhibited with a pretreatment of PD098059, a specific extracellular signal-regulated kinase inhibitor. In our previous report, we proved that lovastatin, a pharmacological inhibitor of p21ras function, also reversed the increase of cortisol level in mutant K-ras stably transfected human adrenocortical cells. Taken together, these findings proved that the active mutant Ras enhanced not only cell proliferation but also steroidogenesis in steroidogenic phenotype cells by activating Raf-MEK-MAPK related signal transduction pathway. Therefore, we believe that K-ras mutants influence regulation of steroidogenesis in adrenocortical cells through RAF-MEK-MAPK pathway

    A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies

    Get PDF
    Genotype imputation methods are now being widely used in the analysis of genome-wide association studies. Most imputation analyses to date have used the HapMap as a reference dataset, but new reference panels (such as controls genotyped on multiple SNP chips and densely typed samples from the 1,000 Genomes Project) will soon allow a broader range of SNPs to be imputed with higher accuracy, thereby increasing power. We describe a genotype imputation method (IMPUTE version 2) that is designed to address the challenges presented by these new datasets. The main innovation of our approach is a flexible modelling framework that increases accuracy and combines information across multiple reference panels while remaining computationally feasible. We find that IMPUTE v2 attains higher accuracy than other methods when the HapMap provides the sole reference panel, but that the size of the panel constrains the improvements that can be made. We also find that imputation accuracy can be greatly enhanced by expanding the reference panel to contain thousands of chromosomes and that IMPUTE v2 outperforms other methods in this setting at both rare and common SNPs, with overall error rates that are 15%–20% lower than those of the closest competing method. One particularly challenging aspect of next-generation association studies is to integrate information across multiple reference panels genotyped on different sets of SNPs; we show that our approach to this problem has practical advantages over other suggested solutions

    Practical Issues in Imputation-Based Association Mapping

    Get PDF
    Imputation-based association methods provide a powerful framework for testing untyped variants for association with phenotypes and for combining results from multiple studies that use different genotyping platforms. Here, we consider several issues that arise when applying these methods in practice, including: (i) factors affecting imputation accuracy, including choice of reference panel; (ii) the effects of imputation accuracy on power to detect associations; (iii) the relative merits of Bayesian and frequentist approaches to testing imputed genotypes for association with phenotype; and (iv) how to quickly and accurately compute Bayes factors for testing imputed SNPs. We find that imputation-based methods can be robust to imputation accuracy and can improve power to detect associations, even when average imputation accuracy is poor. We explain how ranking SNPs for association by a standard likelihood ratio test gives the same results as a Bayesian procedure that uses an unnatural prior assumption—specifically, that difficult-to-impute SNPs tend to have larger effects—and assess the power gained from using a Bayesian approach that does not make this assumption. Within the Bayesian framework, we find that good approximations to a full analysis can be achieved by simply replacing unknown genotypes with a point estimate—their posterior mean. This approximation considerably reduces computational expense compared with published sampling-based approaches, and the methods we present are practical on a genome-wide scale with very modest computational resources (e.g., a single desktop computer). The approximation also facilitates combining information across studies, using only summary data for each SNP. Methods discussed here are implemented in the software package BIMBAM, which is available from http://stephenslab.uchicago.edu/software.html

    New measurement of θ13\theta_{13} via neutron capture on hydrogen at Daya Bay

    Full text link
    This article reports an improved independent measurement of neutrino mixing angle θ13\theta_{13} at the Daya Bay Reactor Neutrino Experiment. Electron antineutrinos were identified by inverse β\beta-decays with the emitted neutron captured by hydrogen, yielding a data-set with principally distinct uncertainties from that with neutrons captured by gadolinium. With the final two of eight antineutrino detectors installed, this study used 621 days of data including the previously reported 217-day data set with six detectors. The dominant statistical uncertainty was reduced by 49%. Intensive studies of the cosmogenic muon-induced 9^9Li and fast neutron backgrounds and the neutron-capture energy selection efficiency, resulted in a reduction of the systematic uncertainty by 26%. The deficit in the detected number of antineutrinos at the far detectors relative to the expected number based on the near detectors yielded sin22θ13=0.071±0.011\sin^22\theta_{13} = 0.071 \pm 0.011 in the three-neutrino-oscillation framework. The combination of this result with the gadolinium-capture result is also reported.Comment: 26 pages, 23 figure
    corecore