2,922 research outputs found

    A fully automatic polygon scaled boundary finite element method for modelling crack propagation

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    An automatic crack propagation remeshing procedure using the polygon scaled boundary FEM is presented. The remeshing algorithm, developed to model any arbitrary shape, is simple yet flexible because only minimal changes are made to the global mesh in each step. Fewer polygon elements are used to predict the final crack path with the algorithm as compared to previous approaches. Two simple polygon optimisation methods which enable the remeshing procedure to model crack propagation more stably are implemented. Four crack propagation benchmarks are modelled to validate the developed method and demonstrate its salient features

    First heterometallic GaIII-DyIII single-molecule magnets: Implication of GaIII in extracting Fe-Dy interaction

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    The compounds of the system [M4M′2(μ3-OH)2(nbdea)4(C6H5CO2)8]·MeCN, where M = GaIII, M′ = DyIII (2), M = FeIII, M′ = YIII (3) are isostructural to the known [Fe4Dy2] compound (1). Those of the system [M4M′4(μ3-OH)4(nbdea)4(m-CH3C6H4CO2)12]·nMeCN, where M = GaIII, M′ = DyIII, n = 4 (5), M = FeIII, M′ = YIII, n = 1 (6) are isostructural to the [Fe4Dy4] compound (4). This allows for comparisons between single ion effects of the paramagnetic ions. The structures were determined using single crystal analysis. Magnetic susceptibility measurements reveal that the GaIII–DyIII compounds 2 and 5 are SMMs. The energy barrier for 2 is close to that for the known isostructural Fe4Dy2 compound (1), but with a significantly increased relaxation time

    JAK2V617F promotes replication fork stalling with disease-restricted impairment of the intra-S checkpoint response

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    Cancers result from the accumulation of genetic lesions, but the cellular consequences of driver mutations remain unclear, especially during the earliest stages of malignancy. The V617F mutation in the JAK2 non-receptor tyrosine kinase (JAK2V617F) is present as an early somatic event in most patients with myeloproliferative neoplasms (MPNs), and the study of these chronic myeloid malignancies provides an experimentally tractable approach to understanding early tumorigenesis. Introduction of exogenous JAK2V617F impairs replication fork progression and is associated with activation of the intra-S checkpoint, with both effects mediated by phosphatidylinositide 3-kinase (PI3K) signaling. Analysis of clonally derived JAK2V617F-positive erythroblasts from MPN patients also demonstrated impaired replication fork progression accompanied by increased levels of replication protein A (RPA)-containing foci. However, the associated intra-S checkpoint response was impaired in erythroblasts from polycythemia vera (PV) patients, but not in those from essential thrombocythemia (ET) patients. Moreover, inhibition of p53 in PV erythroblasts resulted in more gamma-H2Ax (γ-H2Ax)–marked double-stranded breaks compared with in like-treated ET erythroblasts, suggesting the defective intra-S checkpoint function seen in PV increases DNA damage in the context of attenuated p53 signaling. These results demonstrate oncogene-induced impairment of replication fork progression in primary cells from MPN patients, reveal unexpected disease-restricted differences in activation of the intra-S checkpoint, and have potential implications for the clonal evolution of malignancies

    Evolution of asexual and sexual reproduction in the aspergilli

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    Aspergillus nidulans has long-been used as a model organism to gain insights into the genetic basis of asexual and sexual developmental processes both in other members of the genus Aspergillus, and filamentous fungi in general. Paradigms have been established concerning the regulatory mechanisms of conidial development. However, recent studies have shown considerable genome divergence in the fungal kingdom, questioning the general applicability of findings from Aspergillus, and certain longstanding evolutionary theories have been questioned. The phylogenetic distribution of key regulatory elements of asexual reproduction in A. nidulans was investigated in a broad taxonomic range of fungi. This revealed that some proteins were well conserved in the Pezizomycotina (e.g. AbaA, FlbA, FluG, NsdD, MedA, and some velvet proteins), suggesting similar developmental roles. However, other elements (e.g. BrlA) had a more restricted distribution solely in the Eurotiomycetes, and it appears that the genetic control of sporulation seems to be more complex in the aspergilli than in some other taxonomic groups of the Pezizomycotina. The evolution of the velvet protein family is discussed based on the history of expansion and contraction events in the early divergent fungi. Heterologous expression of the A. nidulans abaA gene in Monascus ruber failed to induce development of complete conidiophores as seen in the aspergilli, but did result in increased conidial production. The absence of many components of the asexual developmental pathway from members of the Saccharomycotina supports the hypothesis that differences in the complexity of their spore formation is due in part to the increased diversity of the sporulation machinery evident in the Pezizomycotina. Investigations were also made into the evolution of sex and sexuality in the aspergilli. MAT loci were identified from the heterothallic Aspergillus (Emericella) heterothallicus and Aspergillus (Neosartorya) fennelliae and the homothallic Aspergillus pseudoglaucus (=Eurotium repens). A consistent architecture of the MAT locus was seen in these and other heterothallic aspergilli whereas much variation was seen in the arrangement of MAT loci in homothallic aspergilli. This suggested that it is most likely that the common ancestor of the aspergilli exhibited a heterothallic breeding system. Finally, the supposed prevalence of asexuality in the aspergilli was examined. Investigations were made using A. clavatus as a representative ‘asexual’ species. It was possible to induce a sexual cycle in A. clavatus given the correct MAT1-1 and MAT1-2 partners and environmental conditions, with recombination confirmed utilising molecular markers. This indicated that sexual reproduction might be possible in many supposedly asexual aspergilli and beyond, providing general insights into the nature of asexuality in fungi.National Natural Science Foundation of China 31601446National Research Foundation of Korea 2016010945Intelligent Synthetic Biology Center of Global Frontier Projects 2015M3A6A8065838Biotechnology and Biological Sciences Research CouncilGovernment of IraqMinisterio de Economía y Competitividad BIO2015-67148-

    A Direct Reduction from k-Player to 2-Player Approximate Nash Equilibrium

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    We present a direct reduction from k-player games to 2-player games that preserves approximate Nash equilibrium. Previously, the computational equivalence of computing approximate Nash equilibrium in k-player and 2-player games was established via an indirect reduction. This included a sequence of works defining the complexity class PPAD, identifying complete problems for this class, showing that computing approximate Nash equilibrium for k-player games is in PPAD, and reducing a PPAD-complete problem to computing approximate Nash equilibrium for 2-player games. Our direct reduction makes no use of the concept of PPAD, thus eliminating some of the difficulties involved in following the known indirect reduction.Comment: 21 page

    An Equation of State of a Carbon-Fibre Epoxy Composite under Shock Loading

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    An anisotropic equation of state (EOS) is proposed for the accurate extrapolation of high-pressure shock Hugoniot (anisotropic and isotropic) states to other thermodynamic (anisotropic and isotropic) states for a shocked carbon-fibre epoxy composite (CFC) of any symmetry. The proposed EOS, using a generalised decomposition of a stress tensor [Int. J. Plasticity \textbf{24}, 140 (2008)], represents a mathematical and physical generalisation of the Mie-Gr\"{u}neisen EOS for isotropic material and reduces to this equation in the limit of isotropy. Although a linear relation between the generalised anisotropic bulk shock velocity UsAU^{A}_{s} and particle velocity upu_{p} was adequate in the through-thickness orientation, damage softening process produces discontinuities both in value and slope in the UsAU^{A}_{s}-upu_{p} relation. Therefore, the two-wave structure (non-linear anisotropic and isotropic elastic waves) that accompanies damage softening process was proposed for describing CFC behaviour under shock loading. The linear relationship UsAU^{A}_{s}-upu_{p} over the range of measurements corresponding to non-linear anisotropic elastic wave shows a value of c0Ac^{A}_{0} (the intercept of the UsAU^{A}_{s}-upu_{p} curve) that is in the range between first and second generalised anisotropic bulk speed of sound [Eur. Phys. J. B \textbf{64}, 159 (2008)]. An analytical calculation showed that Hugoniot Stress Levels (HELs) in different directions for a CFC composite subject to the two-wave structure (non-linear anisotropic elastic and isotropic elastic waves) agree with experimental measurements at low and at high shock intensities. The results are presented, discussed and future studies are outlined.Comment: 12 pages, 9 figure

    STAT1 activation in association with JAK2 exon 12 mutations

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    La inclusión de la perspectiva de género en la actividad jurisdiccional es una demanda sostenida de los colectivos feministas y de mujeres, dado que las sentencias tienen un poder performativo y envían un mensaje a la sociedad: “[…] tienen un poder individual y colectivo que impactan en la vida de las personas y conforman la identidad del poder judicial como un actor imprescindible en la construcción de un Estado democrático de derecho” (Suprema Corte de Justicia de la Nación, 2013:7). La incorporación de la perspectiva de género viene a garantizar la igualdad de posiciones (Kessler, 2014) entre mujeres y varones como una meta, trascendiendo la mera igualdad de oportunidades que hasta el presente se ha demostrado insuficiente para que las mujeres consigamos una ciudadanía plena. Al momento de incorporar la perspectiva de género en las sentencias, quienes juzgan deben tener presente en primer lugar, el impacto diferenciado de las normas en base al sexo de las personas. En segundo lugar, la interpretación y aplicación de las leyes en relación con (y en base a) estereotipos de género. Si, por ejemplo, quienes imparten justicia no tienen presentes los estereotipos de género vigentes detrás de las violaciones a los derechos humanos de las mujeres, si no los detectan ni cuestionan, entonces los reproducen. Tal como sostiene Scott (1996) el género es una categoría imprescindible para el análisis social. En tercer lugar, al momento del juzgamiento, se deben tener en cuenta las exclusiones legitimadas por la ley por pensar el mundo en términos binarios y androcéntricos; en cuarto lugar, la distribución no equitativa de recursos y poder que opera entre varones y mujeres en el marco de una organización social patriarcal, y, por último, el trato diferenciado por género legitimado por las propias leyes.Eje 3: Tramas violentas y espacios de exclusión.Instituto de Cultura Jurídic

    Image-based measurement of alveoli volume expansion in an animal model of a diseased lung

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    Currently, there does not exist reliable MV treatment or protocols in critical care to treat acute respiratory diseases, and thus no proven way to optimise care to minimise the mortality, length of stay or cost. The overall approach of this research is to improve protocols by using appropriate computer models that take into account the essential lung mechanics. The aim of this research is to create an automated algorithm for tracking the boundary of individual or groups of alveoli, and to convert this into a pressure volume curve for three different types of alveoli. A technique called in vivo microscopy has been developed by Schiller et al which visualizes the inflation and deflation of individual alveoli in a surfactant deactivation model of lung injury in pigs. Three different types of alveoli were tracked using data from Schiller et al, type I, II and III. These types correspond to healthy alveoli, non-collapsing but partially diseased alveoli, and fully collapsing diseased alveoli respectively. The boundaries of all the alveoli that were tracked, compared well visually to the movies. Pressure versus Area curves were derived for both inflation and deflation, they captured the expected physiological behaviour, and were qualitatively similar to the quasi-static pressure area curves derived in Schiller et al, Quantitative differences are due to the dynamic effects of ventilation which were not investigated in Schiller et al

    Kinetic energy oscillations in annular regions of ultracold neutral plasmas

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    A study of ion equilibration in annular regions of ultracold strontium plasmas is reported. Plasmas are formed by photoionizing laser-cooled atoms with a pulsed dye laser. The experimental probe is spatially-resolved absorption spectroscopy using the 2S1/2-2P1/2 transition of the Sr+ ion. The kinetic energy of the ions is calculated from the Doppler broadening of the spectrum, and it displays clear oscillations during the first microsecond after plasma formation. The oscillations, which are a characteristic of strong coulomb coupling, are fit with a simple phenomenological model incorporating damping and density variation in the plasma
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