576 research outputs found

    Genotype List String: a grammar for describing HLA and KIR genotyping results in a text string

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    Knowledge of an individual's human leukocyte antigen (HLA) genotype is essential for modern medical genetics, and is crucial for hematopoietic stem cell and solid-organ transplantation. However, the high levels of polymorphism known for the HLA genes make it difficult to generate an HLA genotype that unambiguously identifies the alleles that are present at a given HLA locus in an individual. For the last 20 years, the histocompatibility and immunogenetics community has recorded this HLA genotyping ambiguity using allele codes developed by the National Marrow Donor Program (NMDP). While these allele codes may have been effective for recording an HLA genotyping result when initially developed, their use today results in increased ambiguity in an HLA genotype, and they are no longer suitable in the era of rapid allele discovery and ultra-high allele polymorphism. Here, we present a text string format capable of fully representing HLA genotyping results. This Genotype List (GL) String format is an extension of a proposed standard for reporting killer-cell immunoglobulin-like receptor (KIR) genotype data that can be applied to any genetic data that use a standard nomenclature for identifying variants. The GL String format uses a hierarchical set of operators to describe the relationships between alleles, lists of possible alleles, phased alleles, genotypes, lists of possible genotypes, and multilocus unphased genotypes, without losing typing information or increasing typing ambiguity. When used in concert with appropriate tools to create, exchange, and parse these strings, we anticipate that GL Strings will replace NMDP allele codes for reporting HLA genotypes

    Fluctuation induced hopping and spin polaron transport

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    We study the motion of free magnetic polarons in a paramagnetic background of fluctuating local moments. The polaron can tunnel only to nearby regions of local moments when these fluctuate into alignment. We propose this fluctuation induced hopping as a new transport mechanism for the spin polaron. We calculate the diffusion constant for fluctuation induced hopping from the rate at which local moments fluctuate into alignment. The electrical resistivity is then obtained via the Einstein relation. We suggest that the proposed transport mechanism is relevant in the high temperature phase of the Mn pyrochlore colossal magneto resistance compounds and Europium hexaboride.Comment: 8 pages, 3 figure

    Analysing the effects of sliding, adhesive contact on the deformation and stresses induced within a multi-layered elastic solid

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    This paper presents a mathematical model of sliding, adhering contact between a rigid parabolic indenter and a multi-layered elastic solid, which is assumed to comprise of a homogeneous coating bonded through a functionally-graded transitional layer to a homogeneous substrate. The adhesive forces in this investigation are modelled using Lennard-Jones potential and an iterative algorithm is proposed that solves for the contact pressure, surface displacement and sub-surface stresses resultant within the layered solid. The effects of surface adhesion and different material properties such as varying coating/transition layer thickness and coating hardness on the solution of the contact problem are subsequently investigated in detail. The numerical approach presented in this paper demonstrates the significance of having a suitable mathematical representation for the traction distribution along the sliding, adhering contact. It is found that under weakly adhering conditions, the assumption of only Coulombic traction suffices to determine the displacements and subsurface stresses within the multi-layered solid. However, it is noted that stress concentrations within the material begin to propagate through all three layers of the elastic solid with increased surface adhesion, which could potentially induce plasticity and lead to material ploughing under sliding. The proposed model allows us to further investigate and improve our understanding of the combined effects of traction and boundary adhesion in sliding contacts, which can be used to inform the design of materials needed in such conditions

    Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes

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    Nontypeable Haemophilus influenzae (NTHi) colonizes human upper respiratory airways and plays a key role in the course and pathogenesis of acute exacerbations of chronic obstructive pulmonary disease (COPD). Currently, it is not possible to distinguish COPD isolates of NTHi from other clinical isolates of NTHi using conventional genotyping methods. Here, we analysed the core and accessory genome of 568 NTHi isolates, including 40 newly sequenced isolates, to look for genetic distinctions between NTHi isolates from COPD with respect to other illnesses, including otitis media, meningitis and pneumonia. Phylogenies based on polymorphic sites in the core-genome did not show discrimination between NTHi strains collected from different clinical phenotypes. However, pan-genome-wide association studies identified 79 unique NTHi accessory genes that were significantly associated with COPD. Furthermore, many of the COPD-related NTHi genes have known or predicted roles in virulence, transmembrane transport of metal ions and nutrients, cellular respiration and maintenance of redox homeostasis. This indicates that specific genes may be required by NTHi for its survival or virulence in the COPD lung. These results advance our understanding of the pathogenesis of NTHi infection in COPD lungs

    Growth response to ozone of annual species from Mediterranean pastures

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    Ozone (O3) phytotoxicity has been reported on a wide range of plant species. However, scarce information has been provided regarding the sensitivity of semi-natural grassland species, especially those from dehesa Mediterranean grasslands, in spite of their great biological diversity and the high O3 levels recorded in the region. A screening study was carried out in open-top chambers (OTCs) to assess the O3-sensitivity of representative therophytes of these ecosystems based on the response of selected growth-related parameters. Three O3 treatments and 3 OTCs per treatment were used. Legume species were very sensitive to O3, because 78% of the tested species showed detrimental effects on their total biomass relative growth rate (RGR) following their exposure to O3. The Trifolium genus was particularly sensitive showing O3-induced adverse effects on most of the assessed parameters. Gramineae plants were less sensitive than Leguminosae species because detrimental effects on total biomass RGR were only observed in 14% of the assessed species. No relationship was found between relative growth rates when growing in clean air and O3 susceptibility. The implications of these effects on the performance of dehesa acidic grasslands and on the definition of ozone critical levels for the protection of semi-natural vegetation are discussed

    Aluminium substitution induced superstructures in Mg1-xAlxB2 (x = 0.0 to 0.50): An X-ray diffraction study

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    The physical property characterization of Al doped Mg1-xAlxB2 system with x = 0.0 to 0.50 is reported. The results related to phase formation, structural transition, resistivity R(T) and magnetization M(T) measurements are discussed in detail. It is shown that the addition of electrons to MgB2 through Al results in loss of superconductivity. Also seen is a structural transition associated with the collapse of boron layers reflected by the continuous decrease in the c parameter. The main emphasis in this paper is on slow scan X-ray diffraction (XRD) results, which confirm the existence of a superstructure along the c-direction for the x = 0.50 sample. The appearance of some additional peaks, viz. [103], [004], [104] and [112], results in doubling of the lattice parameter along the c-axis. This possibly indicates the alternative ordering of Al and Mg in MgAlB4 separated by hexagonal boron layers but still maintaining the same hexagonal AlB2 type structure.Comment: 17 Pages Text + Figs. To appear in Physica

    IL-15 trans-presentation promotes human NK cell development and differentiation in vivo

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    The in vivo requirements for human natural killer (NK) cell development and differentiation into cytotoxic effectors expressing inhibitory receptors for self–major histocompatability complex class I (MHC-I; killer Ig-like receptors [KIRs]) remain undefined. Here, we dissect the role of interleukin (IL)-15 in human NK cell development using Rag2−/−γc−/− mice transplanted with human hematopoietic stem cells. Human NK cell reconstitution was intrinsically low in this model because of the poor reactivity to mouse IL-15. Although exogenous human IL-15 (hIL-15) alone made little improvement, IL-15 coupled to IL-15 receptor α (IL-15Rα) significantly augmented human NK cells. IL-15–IL-15Rα complexes induced extensive NK cell proliferation and differentiation, resulting in accumulation of CD16+KIR+ NK cells, which was not uniquely dependent on enhanced survival or preferential responsiveness of this subset to IL-15. Human NK cell differentiation in vivo required hIL-15 and progressed in a linear fashion from CD56hiCD16−KIR− to CD56loCD16+KIR−, and finally to CD56loCD16+KIR+. These data provide the first evidence that IL-15 trans-presentation regulates human NK cell homeostasis. Use of hIL-15 receptor agonists generates a robust humanized immune system model to study human NK cells in vivo. IL-15 receptor agonists may provide therapeutic tools to improve NK cell reconstitution after bone marrow transplants, enhance graft versus leukemia effects, and increase the pool of IL-15–responsive cells during immunotherapy strategies

    A meta-analytic review of stand-alone interventions to improve body image

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    Objective Numerous stand-alone interventions to improve body image have been developed. The present review used meta-analysis to estimate the effectiveness of such interventions, and to identify the specific change techniques that lead to improvement in body image. Methods The inclusion criteria were that (a) the intervention was stand-alone (i.e., solely focused on improving body image), (b) a control group was used, (c) participants were randomly assigned to conditions, and (d) at least one pretest and one posttest measure of body image was taken. Effect sizes were meta-analysed and moderator analyses were conducted. A taxonomy of 48 change techniques used in interventions targeted at body image was developed; all interventions were coded using this taxonomy. Results The literature search identified 62 tests of interventions (N = 3,846). Interventions produced a small-to-medium improvement in body image (d+ = 0.38), a small-to-medium reduction in beauty ideal internalisation (d+ = -0.37), and a large reduction in social comparison tendencies (d+ = -0.72). However, the effect size for body image was inflated by bias both within and across studies, and was reliable but of small magnitude once corrections for bias were applied. Effect sizes for the other outcomes were no longer reliable once corrections for bias were applied. Several features of the sample, intervention, and methodology moderated intervention effects. Twelve change techniques were associated with improvements in body image, and three techniques were contra-indicated. Conclusions The findings show that interventions engender only small improvements in body image, and underline the need for large-scale, high-quality trials in this area. The review identifies effective techniques that could be deployed in future interventions
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