462 research outputs found

    Missense variants reveal functional insights into the human ARID family of gene regulators

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    Missense variants are alterations to protein coding sequences that result in amino acid substitutions. They can be deleterious if the amino acid is required for maintaining structure or/and function, but are likely to be tolerated at other sites. Consequently, missense variation within a healthy population can mirror the effects of negative selection on protein structure and function, such that functional sites on proteins are often depleted of missense variants. Advances in high-throughput sequencing have dramatically increased the sample size of available human variation data, allowing for population-wide analysis of selective pressures. In this study, we developed a convenient set of tools, called 1D-to-3D, for visualizing the positions of missense variants on protein sequences and structures. We used these tools to characterize human homologues of the ARID family of gene regulators. ARID family members are implicated in multiple cancer types, developmental disorders, and immunological diseases but current understanding of their mechanistic roles is incomplete. Combined with phylogenetic and structural analyses, our approach allowed us to characterise sites important for protein-protein interactions, histone modification recognition, and DNA binding by the ARID proteins. We find that comparing missense depletion patterns among paralogs can reveal sub-functionalization at the level of domains. We propose that visualizing missense variants and their depletion on structures can serve as a valuable tool for complementing evolutionary and experimental findings

    Spin-correlations and magnetic structure in an Fe monolayer on 5d transition metal surfaces

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    We present a detailed first principles study on the magnetic structure of an Fe monolayer on different surfaces of 5d transition metals. We use the spin-cluster expansion technique to obtain parameters of a spin model, and predict the possible magnetic ground state of the studied systems by employing the mean field approach and in certain cases by spin dynamics calculations. We point out that the number of shells considered for the isotropic exchange interactions plays a crucial role in the determination of the magnetic ground state. In the case of Ta substrate we demonstrate that the out-of-plane relaxation of the Fe monolayer causes a transition from ferromagnetic to antiferromagnetic ground state. We examine the relative magnitude of nearest neighbour Dzyaloshinskii-Moriya (D) and isotropic (J) exchange interactions in order to get insight into the nature of magnetic pattern formations. For the Fe/Os(0001) system we calculate a very large D/J ratio, correspondingly, a spin spiral ground state. We find that, mainly through the leading isotropic exchange and Dzyaloshinskii-Moriya interactions, the inward layer relaxation substantially influences the magnetic ordering of the Fe monolayer. For the Fe/Re(0001) system characterized by large antiferromagnetic interactions we also determine the chirality of the 120120^{\circ} N\'eel-type ground state.Comment: 15 pages, 8 figures, 2 table

    CVaR minimization by the SRA algorithm

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    Using the risk measure CV aR in �nancial analysis has become more and more popular recently. In this paper we apply CV aR for portfolio optimization. The problem is formulated as a two-stage stochastic programming model, and the SRA algorithm, a recently developed heuristic algorithm, is applied for minimizing CV aR

    GINA - A Polarized Neutron Reflectometer at the Budapest Neutron Centre

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    The setup, capabilities and operation parameters of the neutron reflectometer GINA, the recently installed "Grazing Incidence Neutron Apparatus" at the Budapest Neutron Centre, are introduced. GINA, a dance-floor-type, constant-energy, angle-dispersive reflectometer is equipped with a 2D position-sensitive detector to study specular and off-specular scattering. Wavelength options between 3.2 and 5.7 {\AA} are available for unpolarized and polarized neutrons. Spin polarization and analysis are achieved by magnetized transmission supermirrors and radio-frequency adiabatic spin flippers. As a result of vertical focusing by the five-element (pyrolytic graphite) monochromator the reflected intensity from a 20x20 mm sample has doubled. GINA is dedicated to studies of magnetic films and heterostructures, but unpolarized options for non-magnetic films, membranes and other surfaces are also provided. Shortly after its startup, reflectivity values as low as 3x10-5 have been measured on the instrument. The facility is now open for the international user community, but its development is continuing mainly to establish new sample environment options, the spin analysis of off-specularly scattered radiation and further decrease of the background

    Meat production and maintaining biodiversity: Grazing by traditional breeds and crossbred beef cattle in marshes and grasslands

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    Questions: Sustainable rangeland utilization considering traditions and economic reasons is compulsory for harmonising the needs of the agricultural and nature conservation sectors. For proper rangeland management it is crucial to compare the grazing effects of traditional breeds and crossbred animals of the same species that might have different effects on the rangelands. To fill this knowledge gap, in a grazing experiment, we investigated the effect of cattle breeds on the vegetation to test the effects on nature conservation value and agricultural production value. We hypothesized that the effects of cattle grazing on habitat conservation values and forage quality depend on the grazing breed, because breeds differ in selectivity, body size and trampling effect. Location: Marshes and alkaline wet grasslands in Hortobágy National Park, Hungary. Methods: We recorded the percentage cover of vascular plants in three consecutive years in a total of 60 plots in 12 areas grazed by traditional (0.61 AU/ha) and largesized crossbred beef cattle (0.68 AU/ha). Results: We found that the effect of cattle breed on the habitat conservation values and forage quality is dependent on the habitat type. The traditional breed maintained a significantly higher species number and Shannon diversity in marshes than the crossbred beef cattle. Grazing of crossbred cattle led to decreasing moisture indicator values in marsh habitats. Conclusions: Our findings revealed that traditional breeds should be prioritized in the management of wet alkaline grasslands and marshes. Crossbred beef cattle might be a substitute but only in case traditional breeds are not available for the management of alkaline wet grasslands. In marshes, however, we recommend prioritizing the traditional breeds as they maintain higher diversity compared to crossbred beef cattle

    Isolated oxygen defects in 3C- and 4H-SiC: A theoretical study

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    Ab initio calculations in the local-density approximation have been carried out in SiC to determine the possible configurations of the isolated oxygen impurity. Equilibrium geometry and occupation levels were calculated. Substitutional oxygen in 3C-SiC is a relatively shallow effective mass like double donor on the carbon site (O-C) and a hyperdeep double donor on the Si site (O-Si). In 4H-SiC O-C is still a double donor but with a more localized electron state. In 3C-SiC O-C is substantially more stable under any condition than O-Si or interstitial oxygen (O-i). In 4H-SiC O-C is also the most stable one except for heavy n-type doping. We propose that O-C is at the core of the electrically active oxygen-related defect family found by deep level transient spectroscopy in 4H-SiC. The consequences of the site preference of oxygen on the SiC/SiO2 interface are discussed

    Conservation value of the native Hungarian wild grape (Vitis sylvestris Gmel.) evaluated by microsatellite markers

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    Wild grape (Vitis sylvestris GMEL.) has became a highly threatened species in Europe because of habitat loss, competition with alien grape species and intensive forest exploitation. Twenty-three Vitis spp. samples were analysed at 8 microsatellite loci to estimate the genetic diversity of the natural Vitis sylvestris specimens. In order to analyse the morphological traits and to perform molecular analysis, 11 native individuals were sampled from 6 remnant Hungarian habitats of the wild grape. To compare the genetic relationships among the wild specimens, samples from Turkish habitats, as well as cultivars of Vitis vinifera, Vitis labrusca and Vitis riparia were also included. Genetic diversity was higher within the Hungarian wild grape locations, with a mean of He = 0.74, which was higher that of samples originating from a larger area of Turkey, He = 0.69. Most of the Hungarian samples formed a well-defined, separate branch on the NJ tree. Based on the morphological traits and molecular analysis on the territory of Szentendre Island, formerly considered to be one of the largest native locations of wild grape, interspecific hybrids of Vitis sylvestris and Vitis riparia were identified. It can be concluded from the results that most of the Hungarian habitats studied could be valuable for the conservation. This paper reports on Hungarian Vitis sylvestris habitats, providing the first genetic study on diversity and on the relationship of Vitis sylvestris to other Vitis specimens, wild or cultivated, in the central part of the Carpathian Basin
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