331 research outputs found

    Semimetallic behavior in Heusler-type Ru2TaAl and thermoelectric performance improved by off-stoichiometry

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    We report a study of the temperature-dependent electrical resistivity, Seebeck coefficient, thermal conductivity, specific heat, and Al27 nuclear magnetic resonance (NMR) in Heusler-type Ru2TaAl, to shed light on its semimetallic behavior. While the temperature dependence of the electrical resistivity exhibits semiconductorlike behavior, the analysis of low-temperature specific heat reveals a residual Fermi-level density of states (DOS). Both observations can be realized by means of a semimetallic scenario with the Fermi energy located in the pseudogap of the electronic DOS. The NMR Knight shift and spin-lattice relaxation rate show activated behavior at higher temperatures, attributing to the thermally excited carriers across a pseudogap in Ru2TaAl. From the first-principles band structure calculations, we further provide a clear picture that an indirect overlap between electron and hole pockets is responsible for the formation of a pseudogap in the vicinity of the Fermi level of Ru2TaAl. In addition, an effort for improving the thermoelectric performance of Ru2TaAl has been made by investigating the thermoelectric properties of Ru1.95Ta1.05Al. We found significant enhancements in the electrical conductivity and Seebeck coefficient and marked reduction in the thermal conductivity via the off-stoichiomet ric approach. This leads to an increase in the figure-of-merit ZT value from 6.1×10-4 in Ru2TaAl to 3.4×10-3 in Ru1.95Ta1.05Al at room temperature. In this respect, a further improvement of thermoelectric performance based on Ru2TaAl through other off-stoichiometric attempts is highly probable

    Discovering monotonic stemness marker genes from time-series stem cell microarray data

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    © 2015 Wang et al.; licensee BioMed Central Ltd. Background: Identification of genes with ascending or descending monotonic expression patterns over time or stages of stem cells is an important issue in time-series microarray data analysis. We propose a method named Monotonic Feature Selector (MFSelector) based on a concept of total discriminating error (DEtotal) to identify monotonic genes. MFSelector considers various time stages in stage order (i.e., Stage One vs. other stages, Stages One and Two vs. remaining stages and so on) and computes DEtotal of each gene. MFSelector can successfully identify genes with monotonic characteristics.Results: We have demonstrated the effectiveness of MFSelector on two synthetic data sets and two stem cell differentiation data sets: embryonic stem cell neurogenesis (ESCN) and embryonic stem cell vasculogenesis (ESCV) data sets. We have also performed extensive quantitative comparisons of the three monotonic gene selection approaches. Some of the monotonic marker genes such as OCT4, NANOG, BLBP, discovered from the ESCN dataset exhibit consistent behavior with that reported in other studies. The role of monotonic genes found by MFSelector in either stemness or differentiation is validated using information obtained from Gene Ontology analysis and other literature. We justify and demonstrate that descending genes are involved in the proliferation or self-renewal activity of stem cells, while ascending genes are involved in differentiation of stem cells into variant cell lineages.Conclusions: We have developed a novel system, easy to use even with no pre-existing knowledge, to identify gene sets with monotonic expression patterns in multi-stage as well as in time-series genomics matrices. The case studies on ESCN and ESCV have helped to get a better understanding of stemness and differentiation. The novel monotonic marker genes discovered from a data set are found to exhibit consistent behavior in another independent data set, demonstrating the utility of the proposed method. The MFSelector R function and data sets can be downloaded from: http://microarray.ym.edu.tw/tools/MFSelector/

    Inferring stabilizing mutations from protein phylogenies : application to influenza hemagglutinin

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    One selection pressure shaping sequence evolution is the requirement that a protein fold with sufficient stability to perform its biological functions. We present a conceptual framework that explains how this requirement causes the probability that a particular amino acid mutation is fixed during evolution to depend on its effect on protein stability. We mathematically formalize this framework to develop a Bayesian approach for inferring the stability effects of individual mutations from homologous protein sequences of known phylogeny. This approach is able to predict published experimentally measured mutational stability effects (ΔΔG values) with an accuracy that exceeds both a state-of-the-art physicochemical modeling program and the sequence-based consensus approach. As a further test, we use our phylogenetic inference approach to predict stabilizing mutations to influenza hemagglutinin. We introduce these mutations into a temperature-sensitive influenza virus with a defect in its hemagglutinin gene and experimentally demonstrate that some of the mutations allow the virus to grow at higher temperatures. Our work therefore describes a powerful new approach for predicting stabilizing mutations that can be successfully applied even to large, complex proteins such as hemagglutinin. This approach also makes a mathematical link between phylogenetics and experimentally measurable protein properties, potentially paving the way for more accurate analyses of molecular evolution

    Search for a Technicolor omega_T Particle in Events with a Photon and a b-quark Jet at CDF

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    If the Technicolor omega_T particle exists, a likely decay mode is omega_T -> gamma pi_T, followed by pi_T -> bb-bar, yielding the signature gamma bb-bar. We have searched 85 pb^-1 of data collected by the CDF experiment at the Fermilab Tevatron for events with a photon and two jets, where one of the jets must contain a secondary vertex implying the presence of a b quark. We find no excess of events above standard model expectations. We express the result of an exclusion region in the M_omega_T - M_pi_T mass plane.Comment: 14 pages, 2 figures. Available from the CDF server (PS with figs): http://www-cdf.fnal.gov/physics/pub98/cdf4674_omega_t_prl_4.ps FERMILAB-PUB-98/321-

    Mechanochemical modeling of dynamic microtubule growth involving sheet-to-tube transition

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    Microtubule dynamics is largely influenced by nucleotide hydrolysis and the resultant tubulin configuration changes. The GTP cap model has been proposed to interpret the stabilizing mechanism of microtubule growth from the view of hydrolysis effects. Besides, the microtubule growth involves the closure of a curved sheet at its growing end. The curvature conversion also helps to stabilize the successive growth, and the curved sheet is referred to as the conformational cap. However, there still lacks theoretical investigation on the mechanical-chemical coupling growth process of microtubules. In this paper, we study the growth mechanisms of microtubules by using a coarse-grained molecular method. Firstly, the closure process involving a sheet-to-tube transition is simulated. The results verify the stabilizing effect of the sheet structure, and the minimum conformational cap length that can stabilize the growth is demonstrated to be two dimers. Then, we show that the conformational cap can function independently of the GTP cap, signifying the pivotal role of mechanical factors. Furthermore, based on our theoretical results, we describe a Tetris-like growth style of microtubules: the stochastic tubulin assembly is regulated by energy and harmonized with the seam zipping such that the sheet keeps a practically constant length during growth.Comment: 23 pages, 7 figures. 2 supporting movies have not been uploaded due to the file type restriction

    Interferon-α Improves Phosphoantigen-Induced Vγ9Vδ2 T-Cells Interferon-γ Production during Chronic HCV Infection

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    In chronic HCV infection, treatment failure and defective host immune response highly demand improved therapy strategies. Vγ9Vδ2 T-cells may inhibit HCV replication in vitro through IFN-γ release after Phosphoantigen (PhAg) stimulation. The aim of our work was to analyze Vγ9Vδ2 T-cell functionality during chronic HCV infection, studying the role of IFN-α on their function capability. IFN-γ production by Vγ9Vδ2 T-cells was analyzed in vitro in 24 HCV-infected patients and 35 healthy donors (HD) after PhAg stimulation with or without IFN-α. The effect of in vivo PhAg/IFN-α administration on plasma IFN-γ levels was analyzed in M. fascicularis monkeys. A quantitative analysis of IFN-γ mRNA level and stability in Vγ9Vδ2 T-cells was also evaluated. During chronic HCV infection, Vγ9Vδ2 T-cells showed an effector/activated phenotype and were significantly impaired in IFN-γ production. Interestingly, IFN-α was able to improve their IFN-γ response to PhAg both in vitro in HD and HCV-infected patients, and in vivo in Macaca fascicularis primates. Finally, IFN-α increased IFN-γ-mRNA transcription and stability in PhAg-activated Vγ9Vδ2 T-cells. Altogether our results show a functional impairment of Vγ9Vδ2 T-cells during chronic HCV infection that can be partially restored by using IFN-α. A study aimed to evaluate the antiviral impact of PhAg/IFN-α combination may provide new insight in designing possible combined strategies to improve HCV infection treatment outcome

    Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20

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    Toll-like receptor (TLR) signaling is linked to autophagy that facilitates elimination of intracellular pathogens. However, it is largely unknown whether autophagy controls TLR signaling. Here, we report that poly(I:C) stimulation induces selective autophagic degradation of the TLR adaptor molecule TRIF and the signaling molecule TRAF6, which is revealed by gene silencing of the ubiquitin-editing enzyme A20. This type of autophagy induced formation of autophagosomes and could be suppressed by an autophagy inhibitor and lysosomal inhibitors. However, this autophagy was not associated with canonical autophagic processes, including involvement of Beclin-1 and conversion of LC3-I to LC3-II. Through screening of TRIF-interacting ‘autophagy receptors’ in human cells, we identified that NDP52 mediated the selective autophagic degradation of TRIF and TRAF6 but not TRAF3. NDP52 was polyubiquitinated by TRAF6 and was involved in aggregation of TRAF6, which may result in the selective degradation. Intriguingly, only under the condition of A20 silencing, NDP52 could effectively suppress poly(I:C)-induced proinflammatory gene expression. Thus, this study clarifies a selective autophagic mechanism mediated by NDP52 that works downstream of TRIF–TRAF6. Furthermore, although A20 is known as a signaling fine-tuner to prevent excess TLR signaling, it paradoxically downregulates the fine-tuning effect of NDP52 on TLR signaling
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