1,318 research outputs found

    Empirical Bayes risk evaluation with type II censored data

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    Empirical Bayes estimators for the scale parameter in a Weibull, Raleigh or an exponential distribution with type II censored data are developed. These estimators are derived by the matching moment method, the maximum likelihood method and by modifying the geometric mean estimators developed by Dey and Kuo (1991). The empirical Bayes risks for these estimators and the Bayes rules are evaluated by extensive simulation. Often, the moment empirical Bayes estimator has the smallest empirical Bayes risk. The cases that the modified geometric mean estimator has the smallest empirical Bayes risk are also identified. We also obtain the risk comparisons for various empirical Bayes estimators when one of the parameters in the hyperprior is knownNaval Postgraduate School, Monterey, CAhttp://archive.org/details/empiricalbayesri00kuolO&MN, Direct FundingNAApproved for public release; distribution is unlimited

    First-order magnetic and structural phase transitions in Fe1+y_{1+y}Sex_xTe1x_{1-x}

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    We use bulk magnetic susceptibility, electronic specific heat, and neutron scattering to study structural and magnetic phase transitions in Fe1+y_{1+y}Se% x_xTe1x_{1-x}. Fe1.068_{1.068}Te exhibits a first order phase transition near 67 K with a tetragonal to monoclinic structural transition and simultaneously develops a collinear antiferromagnetic (AF) order responsible for the entropy change across the transition. Systematic studies of FeSe%_{1-x}Tex_x system reveal that the AF structure and lattice distortion in these materials are different from those of FeAs-based pnictides. These results call into question the conclusions of present density functional calculations, where FeSe1x_{1-x}Tex_x and FeAs-based pnictides are expected to have similar Fermi surfaces and therefore the same spin-density-wave AF order.Comment: 5 pages, 3 figure

    Assessing Combinability of Phylogenomic Data Using Bayes Factors

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    With the rapid reduction in sequencing costs of high-throughput genomic data, it has become commonplace to use hundreds of genes to infer phylogeny of any study system. While sampling a large number of genes has given us a tremendous opportunity to uncover previously unknown relationships and improve phylogenetic resolution, it also presents us with new challenges when the phylogenetic signal is confused by differences in the evolutionary histories of sampled genes. Given the incorporation of accurate marginal likelihood estimation methods into popular Bayesian software programs, it is natural to consider using the Bayes Factor (BF) to compare different partition models in which genes within any given partition subset share both tree topology and edge lengths. We explore using marginal likelihood to assess data subset combinability when data subsets have varying levels of phylogenetic discordance due to deep coalescence events among genes (simulated within a species tree), and compare the results with our recently described phylogenetic informational dissonance index (D) estimated for each data set. BF effectively detects phylogenetic incongruence and provides a way to assess the statistical significance of D values. We use BFs to assess data combinability using an empirical data set comprising 56 plastid genes from the green algal order Volvocales. We also discuss the potential need for calibrating BFs and demonstrate that BFs used in this study are correctly calibrated

    Overcoming cisplatin resistance by mTOR inhibitor in lung cancer

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    BACKGROUND: Cisplatin resistance is complex and involves several different mechanisms. Employing cDNA microarray analysis, we have found that cisplatin resistant cells share the common characteristic of increase in ribosomal proteins and elongation factors. We hypothesize that in order to survive cisplatin treatment, cells have to synthesize DNA repair proteins, antiapoptotic proteins and growth-stimulating proteins. Thus, by blocking the translation of these proteins, one should be able to restore cisplatin sensitivity. We have studied the role of CCI-779, an ester analog of rapamycin which is known to inhibit translation by disabling mTOR, in restoring cisplatin sensitivity in a panel of cisplatin resistant cell lines. We have also determined the role of CCI-779 in P-gp1 and MRP1 mediated resistance. RESULTS: Our data show that CCI-779 possess antiproliferative effects in both cisplatin sensitive and resistant cell lines, but shows no effect in P-gp1 and MRP1 overexpressing cell lines. Importantly, CCI-779 at 10 ng/ml (less that 10% of the growth inhibitory effect) can increase the growth inhibition of cisplatin by 2.5–6 fold. Moreover, CCI-779 also enhances the apoptotic effect of cisplatin in cisplatin resistant cell lines. In these resistant cells, adding CCI-779 decreases the amount of 4E-BP phosphorylation and p-70S6 kinase phosphorylation as well as lower the amount of elongation factor while cisplatin alone has no effect. However, CCI-779 can only reverse P-gp mediated drug resistance at a higher dose(1 ug/ml). CONCLUSION: We conclude that CCI-779 is able to restore cisplatin sensitivity in small cell lung cancer cell lines selected for cisplatin resistance as well as cell lines derived from patients who failed cisplatin. These findings can be further explored for future clinical use. On the other hand, CCI-779 at achievable clinical concentration, has no growth inhibitory effect in P-gp1 or MRP1 overexpressing cells. Furthermore, CCI-779 also appears to be a weak MDR1 reversal agent. Thus, it is not a candidate to use in MDR1 or MRP1 overexpressing cells

    Dosage Compensation of the X Chromosomes in Bovine Germline, Early Embryos, and Somatic Tissues

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    Dosage compensation of the mammalian X chromosome (X) was proposed by Susumu Ohno as a mechanism wherein the inactivation of one X in females would lead to doubling the expression of the other. This would resolve the dosage imbalance between eutherian females (XX) versus male (XY) and between a single active X versus autosome pairs (A). Expression ratio of X- and A-linked genes has been relatively well studied in humans and mice, despite controversial results over the existence of upregulation of X-linked genes. Here we report the first comprehensive test of Ohno’s hypothesis in bovine preattachment embryos, germline, and somatic tissues. Overall an incomplete dosage compensation (0.5 \u3c X:A \u3c 1) of expressed genes and an excess X dosage compensation (X:A \u3e 1) of ubiquitously expressed “dosage-sensitive” genes were seen. No significant differences in X:A ratios were observed between bovine female and male somatic tissues, further supporting Ohno’s hypothesis. Interestingly, preimplantation embryos manifested a unique pattern of X dosage compensation dynamics. Specifically, X dosage decreased after fertilization, indicating that the sperm brings in an inactive X to the matured oocyte. Subsequently, the activation of the bovine embryonic genome enhanced expression of X-linked genes and increased the X dosage. As a result, an excess compensation was exhibited from the 8-cell stage to the compact morula stage. The X dosage peaked at the 16-cell stage and stabilized after the blastocyst stage. Together, our findings confirm Ohno’s hypothesis of X dosage compensation in the bovine and extend it by showing incomplete and over-compensation for expressed and “dosage-sensitive” genes, respectively

    Cholinergic Input Is Required during Embryonic Development to Mediate Proper Assembly of Spinal Locomotor Circuits

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    SummaryRhythmic limb movements are controlled by pattern-generating neurons within the ventral spinal cord, but little is known about how these locomotor circuits are assembled during development. At early stages of embryogenesis, motor neurons are spontaneously active, releasing acetylcholine that triggers the depolarization of adjacent cells in the spinal cord. To investigate whether acetylcholine-driven activity is required for assembly of the central pattern-generating (CPG) circuit, we studied mice lacking the choline acetyltransferase (ChAT) enzyme. Our studies show that a rhythmically active spinal circuit forms in ChAT mutants, but the duration of each cycle period is elongated, and right-left and flexor-extensor coordination are abnormal. In contrast, blocking acetylcholine receptors after the locomotor network is wired does not affect right-left or flexor-extensor coordination. These findings suggest that the cholinergic neurotransmitter pathway is involved in configuring the CPG during a transient period of development

    Effectiveness and safety of sofosbuvir plus ribavirin for the treatment of HCV genotype 2 infection: results of the real-world, clinical practice HCV-TARGET study

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    Due to a high efficacy in clinical trials, sofosbuvir (SOF) and ribavirin (RBV) for 12 or 16 weeks is recommended for treatment of patients with HCV genotype (GT) 2 infection. We investigated safety and effectiveness of these regimens for GT2 in HCV-TARGET participants