197 research outputs found

    Structural disjoining potential for grain boundary premelting and grain coalescence from molecular-dynamics simulations

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    We describe a molecular dynamics framework for the direct calculation of the short-ranged structural forces underlying grain-boundary premelting and grain-coalescence in solidification. The method is applied in a comparative study of (i) a Sigma 9 120 degress twist and (ii) a Sigma 9 {411} symmetric tilt boundary in a classical embedded-atom model of elemental Ni. Although both boundaries feature highly disordered structures near the melting point, the nature of the temperature dependence of the width of the disordered regions in these boundaries is qualitatively different. The former boundary displays behavior consistent with a logarithmically diverging premelted layer thickness as the melting temperature is approached from below, while the latter displays behavior featuring a finite grain-boundary width at the melting point. It is demonstrated that both types of behavior can be quantitatively described within a sharp-interface thermodynamic formalism involving a width-dependent interfacial free energy, referred to as the disjoining potential. The disjoining potential for boundary (i) is calculated to display a monotonic exponential dependence on width, while that of boundary (ii) features a weak attractive minimum. The results of this work are discussed in relation to recent simulation and theoretical studies of the thermodynamic forces underlying grain-boundary premelting.Comment: 24 pages, 8 figures, 1 tabl

    A swollen phase observed between the liquid-crystalline phase and the interdigitated phase induced by pressure and/or adding ethanol in DPPC aqueous solution

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    A swollen phase, in which the mean repeat distance of lipid bilayers is larger than the other phases, is found between the liquid-crystalline phase and the interdigitated gel phase in DPPC aqueous solution. Temperature, pressure and ethanol concentration dependences of the structure were investigated by small-angle neutron scattering, and a bending rigidity of lipid bilayers was by neutron spin echo. The nature of the swollen phase is similar to the anomalous swelling reported previously. However, the temperature dependence of the mean repeat distance and the bending rigidity of lipid bilayers are different. This phase could be a precursor to the interdigitated gel phase induced by pressure and/or adding ethanol.Comment: 7 pages, 6 figure

    Construction of a nurse shark (Ginglymostoma cirratum) bacterial artificial chromosome (BAC) library and a preliminary genome survey

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    BACKGROUND: Sharks are members of the taxonomic class Chondrichthyes, the oldest living jawed vertebrates. Genomic studies of this group, in comparison to representative species in other vertebrate taxa, will allow us to theorize about the fundamental genetic, developmental, and functional characteristics in the common ancestor of all jawed vertebrates. AIMS: In order to obtain mapping and sequencing data for comparative genomics, we constructed a bacterial artificial chromosome (BAC) library for the nurse shark, Ginglymostoma cirratum. RESULTS: The BAC library consists of 313,344 clones with an average insert size of 144 kb, covering ~4.5 × 10(10 )bp and thus providing an 11-fold coverage of the haploid genome. BAC end sequence analyses revealed, in addition to LINEs and SINEs commonly found in other animal and plant genomes, two new groups of nurse shark-specific repetitive elements, NSRE1 and NSRE2 that seem to be major components of the nurse shark genome. Screening the library with single-copy or multi-copy gene probes showed 6–28 primary positive clones per probe of which 50–90% were true positives, demonstrating that the BAC library is representative of the different regions of the nurse shark genome. Furthermore, some BAC clones contained multiple genes, making physical mapping feasible. CONCLUSION: We have constructed a deep-coverage, high-quality, large insert, and publicly available BAC library for a cartilaginous fish. It will be very useful to the scientific community interested in shark genomic structure, comparative genomics, and functional studies. We found two new groups of repetitive elements specific to the nurse shark genome, which may contribute to the architecture and evolution of the nurse shark genome

    Common Variants in the COL4A4 Gene Confer Susceptibility to Lattice Degeneration of the Retina

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    Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8×10−6, OR = 0.63 and Pc = 1.0×10−5, OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina

    Genome-wide association analysis with selective genotyping identifies candidate loci for adult height at 8q21.13 and 15q22.33-q23 in Mongolians

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    We performed a genome-wide association study with 23,465 microsatellite markers to identify genes related to adult height. Selective genotyping was applied to extremely tall and extremely short individuals from the Khalkh-Mongolian population. Two loci, 8q21.13 and 15q22.33, which showed the strongest association with microsatellites were subjected to further analyses of SNPs in 782 tall and 773 short individuals. The most significant association was observed with SNP rs2220456 at 8q21.13 (P = 0.000016). In the LD block at 15q22.32, SNP rs8038652 located in intron 1 of IQCH was strongly associated (P = 0.0003), especially the AA genotype of the SNP under a recessive model was strongly associated with adult height (P = 0.000046)

    A Novel System of Polymorphic and Diverse NK Cell Receptors in Primates

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    There are two main classes of natural killer (NK) cell receptors in mammals, the killer cell immunoglobulin-like receptors (KIR) and the structurally unrelated killer cell lectin-like receptors (KLR). While KIR represent the most diverse group of NK receptors in all primates studied to date, including humans, apes, and Old and New World monkeys, KLR represent the functional equivalent in rodents. Here, we report a first digression from this rule in lemurs, where the KLR (CD94/NKG2) rather than KIR constitute the most diverse group of NK cell receptors. We demonstrate that natural selection contributed to such diversification in lemurs and particularly targeted KLR residues interacting with the peptide presented by MHC class I ligands. We further show that lemurs lack a strict ortholog or functional equivalent of MHC-E, the ligands of non-polymorphic KLR in “higher” primates. Our data support the existence of a hitherto unknown system of polymorphic and diverse NK cell receptors in primates and of combinatorial diversity as a novel mechanism to increase NK cell receptor repertoire

    Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients

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    <p>Abstract</p> <p>Background</p> <p>The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.</p> <p>Methods</p> <p>Cancer patients (n = 360) were selected retrospectively from the RadGenomics project. Adverse effects within 3 months of radiotherapy completion were graded using the National Cancer Institute Common Toxicity Criteria; high grade group were grade 3 or more (n = 180), low grade group were grade 1 or less (n = 180). Pooled genomic DNA (gDNA) (n = 90 from each group) was screened using 23,244 microsatellites. Markers with different inter-group frequencies (Fisher exact test <it>P </it>< 0.05) were analyzed using the remaining pooled gDNA. Silencing RNA treatment was performed in cultured normal human skin fibroblasts.</p> <p>Results</p> <p>Forty-seven markers had positive association values; including one in the <it>SEMA3A </it>promoter region (P = 1.24 × 10<sup>-5</sup>). <it>SEMA3A </it>knockdown enhanced radiation resistance.</p> <p>Conclusions</p> <p>This study identified 47 putative radiosensitivity markers, and suggested a role for <it>SEMA3A </it>in radiosensitivity.</p
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