928 research outputs found

    Direct Synthesis of G-2N

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    The synthesis of angularly fused quinone natural products has been achieved using a photoenolization reaction and a Diels−Alder reaction in the key carbon−carbon bond forming steps

    A pathway analysis of genome-wide association study highlights novel type 2 diabetes risk pathways.

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    Genome-wide association studies (GWAS) have been widely used to identify common type 2 diabetes (T2D) variants. However, the known variants just explain less than 20% of the overall estimated genetic contribution to T2D. Pathway-based methods have been applied into T2D GWAS datasets to investigate the biological mechanisms and reported some novel T2D risk pathways. However, few pathways were shared in these studies. Here, we performed a pathway analysis using the summary results from a large-scale meta-analysis of T2D GWAS to investigate more genetic signals in T2D. Here, we selected PLNK and VEGAS to perform the gene-based test and WebGestalt to perform the pathway-based test. We identified 8 shared KEGG pathways after correction for multiple tests in both methods. We confirm previous findings, and highlight some new T2D risk pathways. We believe that our results may be helpful to study the genetic mechanisms of T2D

    Long-term mechanical behavior of Yucca Mountain tuff and its variability

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    The study of the long term mechanical behavior of Yucca Mountain tuffs is important for several reasons. Long term stability of excavations will affect accessibility (e.g. for inspection purposes), and retrievability. Long term instabilities may induce loading of drip shields and/or emplaced waste, thus affecting drip shield and/or waste package corrosion. Failure of excavations will affect airflow, may affect water flow, and may affect temperature distributions. The long term mechanical behavior of “hard” rocks remains an elusive topic, loaded with uncertainties. A variety of approaches have been used to improve the understanding of this complex subject, but it is doubtful that it has reached a stage where firm predictions can be considered feasible

    A New Single-blade Based Hybrid CFD Method for Hovering and Forward-flight Rotor Computation

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    AbstractA hybrid Euler/full potential/Lagrangian wake method, based on single-blade simulation, for predicting unsteady aerodynamic flow around helicopter rotors in hover and forward flight has been developed. In this method, an Euler solver is used to model the near wake evolution and transonic flow phenomena in the vicinity of the blade, and a full potential equation (FPE) is used to model the isentropic potential flow region far away from the rotor, while the wake effects of other blades and the far wake are incorporated into the flow solution as an induced inflow distribution using a Lagrangian based wake analysis. To further reduce the execution time, the computational fluid dynamics (CFD) solution and rotor wake analysis (including induced velocity update) are conducted parallelly, and a load balancing strategy is employed to account for the information exchange between two solvers. By the developed method, several hover and forward-flight cases on Caradonna-Tung and Helishape 7A rotors are performed. Good agreements of the loadings on blade surface with available measured data demonstrate the validation of the method. Also, the CPU time required for different computation runs is compared in the paper, and the results show that the present hybrid method is superior to conventional CFD method in time cost, and will be more efficient with the number of blades increasing

    Novel KRIT1/CCM1 and MGC4607/CCM2 Gene Variants in Chinese Families With Cerebral Cavernous Malformations

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    Familial cerebral cavernous malformations (CCMs) are autosomal dominant disorders characterized by hemorrhagic strokes, recurrent headache, epilepsy, and focal neurological deficits. Genetic variants in KRIT1/CCM1, MGC4607/CCM2, and PDCD10/CCM3 genes contribute to CCMs. The clinical information of two Chinese families with CCMs was collected. MRI and video-electroencephalography were performed. Genetic variants of CCM1, CCM2, and CCM3 genes were investigated by exome sequencing. The patients were presented with recurrent epilepsy or headache. Susceptibility-weighted images of brains showed many dark dots, while video-electroencephalography revealed many spikes from multiple brain regions of patients. Exome sequencing revealed a novel CCM1 genetic variant (c.1599_1601TGAdel, p.Asp533del) and a novel CCM2 genetic variant (c.773delA, p.K258fsX34) in Family one and Family two, respectively; cosegregation existed in these two families. The two family members presented typical CCMs symptoms. These two novel genetic variants in CCM1 and CCM2 genes were the causation of CCM in the two Chinese families, and our data enriched the genetic variant spectrum of CCM genes

    Parallelization of dissipative particle dynamics simulation

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    The dissipative particle dynamics simulation is usually used to study polymer in mesoscopic space. The traditional methods are resource intensive, especially when the scale of research is large. Therefore, improving computing efficiency is a key point in this research area. Two major issues are addressed in this paper. First, the DPD methods are analysed and the most time-consuming parts are identified: conservative force, dissipative force and random force. Second, we describe how to parallelize the existing serial application in the Windows Compute Cluster Server (WCCS) platform. The results show that the parallel algorithm not only effectively shortens the computing time, but also improves the resource utilization rate.<br /

    Methods of MicroRNA Promoter Prediction and Transcription Factor Mediated Regulatory Network

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    MicroRNAs (miRNAs) are short (~22 nucleotides) noncoding RNAs and disseminated throughout the genome, either in the intergenic regions or in the intronic sequences of protein-coding genes. MiRNAs have been proved to play important roles in regulating gene expression. Hence, understanding the transcriptional mechanism of miRNA genes is a very critical step to uncover the whole regulatory network. A number of miRNA promoter prediction models have been proposed in the past decade. This review summarized several most popular miRNA promoter prediction models which used genome sequence features, or other features, for example, histone markers, RNA Pol II binding sites, and nucleosome-free regions, achieved by high-throughput sequencing data. Some databases were described as resources for miRNA promoter information. We then performed comprehensive discussion on prediction and identification of transcription factor mediated microRNA regulatory networks

    Molecular analysis and expression of phenylalanine ammonia-lyase from poinsettia (Euphorbia pulcherrima willd.)

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    Phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) is a key regulatory enzyme that link primary and secondary metabolism in plants by catalyzing the conversion of l-phenylalanine to cinnamic acid. In this study, the cDNA and genomic DNA of PAL (named EpPAL) in poinsettia (Euphorbia pulcherrima willd.) were isolated and submitted in GenBank with accession number FJ594466 and FJ943503, respectively. The full-length of cDNA was 2429 bp with a poly (A) tail and contains a 2166-bp open reading frame (ORF) encoding 721 amino acids. The sequence of genomic DNA was 3315 bp, and the transcript was divided into two exons by an 886-bp long intron which located at 416 bp downstream initiation codon. Expression analysis of EpPAL in poinsettia revealed that expression levels were higher in roots and bracts, but lower in stems and green leaves. Meanwhile, expression levels increased in the order: green leaves - turning color leaves - bracts, which were consistent with their anthocyanin content during growth and development of bracts. The curve of diurnal variation of EpPAL expression level in bracts exhibited two highest peaks at 9:00 and 18:00, respectively, and reached the lowest level at 12:00 in a clear day. With the maturation and senescence of bracts, expression levels reduced gradually in both green leaves and bracts, but decreased more rapidly in bracts than green leaves.Keywords: Cloning, expression, phenylalanine ammonia-lyase, poinsetti
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