82 research outputs found

    Compliance and Fatigue Life Analysis of U-shaped Flexure Hinge

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    Implication of Existence of Hybrid stars and Theoretical Expectation of Submillisecond Pulsars

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    We derive the bulk viscous damping timescale of hybrid stars, neutron stars with quark matter core. The r-mode instability windows of the stars show that the theoretical results are consistent with the rapid rotation pulsar data, which may give an indication for the existence of quark matter in the interior of neutron stars. Hybrid stars instead of neutron or strange stars may lead to submillisecond pulsars.Comment: 9 pages,3 figures, accepted by New Astronom

    KNL1 is a prognostic and diagnostic biomarker related to immune infiltration in patients with uterine corpus endometrial carcinoma

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    BackgroundThe incidence and mortality of uterine corpus endometrial carcinoma (UCEC) are increasing yearly. There is currently no screening test for UCEC, and progress in its treatment is limited. It is important to identify new biomarkers for screening, diagnosing and predicting the outcomes of UCEC. A large number of previous studies have proven that KNL1 is crucial in the development of lung cancer, colorectal cancer and cervical cancer, but there is a lack of studies about the role of KNL1 in the development of UCEC.MethodsThe mRNA and protein expression data of KNL1 in The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and UALCAN databases and related clinical data were used to analyze the expression differences and clinical correlations of KNL1 in UCEC. A total of 108 clinical samples were collected, and the results of bioinformatics analysis were verified by immunohistochemistry. KNL1 and its related differentially expressed genes were used to draw a volcano map, construct a PPI protein interaction network, and perform gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA) and immune infiltration analysis to predict the function of KNL1 during UCEC progression. The prognostic data of TCGA and 108 clinical patients were used to analyze the correlation of KNL1 expression with the survival of patients, and KM survival curves were drawn. The UCEC cell lines Ishikawa and Hec-1-A were used to verify the function of KNL1.ResultsKNL1 is significantly overexpressed in UCEC and is associated with a poor prognosis. KNL1 overexpression is closely related to cell mitosis, the cell cycle and other functions and is correlated with the International Federation of Gynecology and Obstetrics (FIGO) stage, histological grade and other characteristics of UCEC patients. Knockdown of KNL1 expression in UCEC cell lines can inhibit their proliferation, invasion, metastasis and other phenotypes.ConclusionKNL1 is a prognostic and diagnostic biomarker associated with immune evasion in patients with UCEC

    Attenuated Glial Reactivity on Topographically Functionalized Poly(3,4-Ethylenedioxythiophene):P-Toluene Sulfonate (PEDOT:PTS) Neuroelectrodes Fabricated by Microimprint Lithography

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    Following implantation, neuroelectrode functionality is susceptible to deterioration via reactive host cell response and glial scar-induced encapsulation. Within the neuroengineering community, there is a consensus that the induction of selective adhesion and regulated cellular interaction at the tissue–electrode interface can significantly enhance device interfacing and functionality in vivo. In particular, topographical modification holds promise for the development of functionalized neural interfaces to mediate initial cell adhesion and the subsequent evolution of gliosis, minimizing the onset of a proinflammatory glial phenotype, to provide long-term stability. Herein, a low-temperature microimprint-lithography technique for the development of micro-topographically functionalized neuroelectrode interfaces in electrodeposited poly(3,4-ethylenedioxythiophene):p-toluene sulfonate (PEDOT:PTS) is described and assessed in vitro. Platinum (Pt) microelectrodes are subjected to electrodeposition of a PEDOT:PTS microcoating, which is subsequently topographically functionalized with an ordered array of micropits, inducing a significant reduction in electrode electrical impedance and an increase in charge storage capacity. Furthermore, topographically functionalized electrodes reduce the adhesion of reactive astrocytes in vitro, evident from morphological changes in cell area, focal adhesion formation, and the synthesis of proinflammatory cytokines and chemokine factors. This study contributes to the understanding of gliosis in complex primary mixed cell cultures, and describes the role of micro-topographically modified neural interfaces in the development of stable microelectrode interfaces

    Mapping genomic loci implicates genes and synaptic biology in schizophrenia

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    Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead
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