658 research outputs found

    Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting aspects of the autism pathology.

    Get PDF
    Autism spectrum disorders (ASDs) are complex and heterogeneous developmental disabilities affecting an ever-increasing number of children worldwide. The diverse manifestations and complex, largely genetic aetiology of ASDs pose a major challenge to the identification of unifying neuropathological features. Here we describe the neurodevelopmental defects in mice that carry deleterious alleles of the Wdfy3 gene, recently recognized as causative in ASDs. Loss of Wdfy3 leads to a regionally enlarged cerebral cortex resembling early brain overgrowth described in many children on the autism spectrum. In addition, affected mouse mutants display migration defects of cortical projection neurons, a recognized cause of epilepsy, which is significantly comorbid with autism. Our analysis of affected mouse mutants defines an important role for Wdfy3 in regulating neural progenitor divisions and neural migration in the developing brain. Furthermore, Wdfy3 is essential for cerebral expansion and functional organization while its loss-of-function results in pathological changes characteristic of ASDs

    Myeloid DAP12-associating lectin (MDL)-1 regulates synovial inflammation and bone erosion associated with autoimmune arthritis.

    Get PDF
    DNAX adaptor protein 12 (DAP12) is a trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells. Absence of functional Dap12 results in osteoclast defects and bone abnormalities. Because DAP12 has no extracelluar binding domains, it must pair with cell surface receptors for signal transduction. There are at least 15 known DAP12-associating cell surface receptors with distinct temporal and cell type-specific expression patterns. Our aim was to determine which receptors may be important in DAP12-associated bone pathologies. Here, we identify myeloid DAP12-associating lectin (MDL)-1 receptor (also known as CLEC5A) as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation. Activation of MDL-1 leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joint and promotes bone erosion. Functional blockade of MDL-1 receptor via Mdl1 deletion or treatment with MDL-1-Ig fusion protein reduces the clinical signs of autoimmune joint inflammation. These findings suggest that MDL-1 receptor may be a therapeutic target for treatment of immune-mediated skeletal disorders

    Prediction of knot size in uneven-sized Norway spruce stands in Sweden

    Get PDF
    The size of knots is negatively correlated with bending strength in sawn timber and it is therefore used as a quality grading criterion in national roundwood grading standards. Some standards even use the size of the largest knot as the sole estimate for individual log knottiness. The size of knots is determined by crown horizontal extension, which in turn is dependent on the impact of competing trees. Thus, with knot size models that are competition-dependent, roundwood quality due to knottiness can be simulated for different management alternatives. However, these types of models, calibrated on uneven-sized Norway spruce in Fennoscandia, are currently not available. Therefore, the objective of this study is to develop a competition-dependent model framework for prediction of the largest knot size per stem height section, for application within uneven-sized Norway spruce stands. Data from terrestrial laser scanning of an uneven-sized stand in southern Sweden are used to calibrate a modular prediction framework, consisting of interlinked allometric statistical models. Alternative framework sub-models are presented and the preferred model combination can be selected according to context and available input data. The flexible modular format enables further development of separate sub-components for adaptation to growing conditions not covered by the current calibration range

    One-dimensional magnetic fluctuations in the spin-2 triangular lattice \alpha-NaMnO2

    Full text link
    The S=2 anisotropic triangular lattice alpha-NaMnO2 is studied by neutron inelastic scattering. Antiferromagnetic order occurs at T ~ 45 K with opening of a spin gap. The spectral weight of the magnetic dynamics above the gap (Delta ~ 7.5 meV) has been analysed by the single-mode approximation. Excellent agreement with the experiment is achieved when a dominant exchange interaction (|J|/k_B ~ 73 K), along the monoclinic b-axis and a sizeable easy-axis magnetic anisotropy (|D|/k_B ~ 3 K) are considered. Despite earlier suggestions for two-dimensional spin interactions, the dynamics illustrate strongly coupled antiferromagnetic S=2 chains and cancellation of the interchain exchange due to the lattice topology. alpha-NaMnO2 therefore represents a model system where the geometric frustration is resolved through the lowering of the dimensionality of the spin interactions.Comment: 4 pages, 4 figures, to be published in Physical Review Letter

    Structural and electrical characterization of SiO2 gate dielectrics deposited from solutions at moderate temperatures in air

    Get PDF
    Silicon dioxide (SiO2) is the most widely used dielectric for electronic applications. It is usually produced by thermal oxidation of silicon or by using a wide range of vacuum-based techniques. By default, the growth of SiO2 by thermal oxidation of silicon, requires the use of Si substrates whereas the other deposition techniques either produce low quality or poor interface material and mostly require high deposition or annealing temperatures. Recent investigations therefore have focused on the development of alternative deposition paradigms based on solutions. Here, we report the deposition of SiO2 thin film dielectrics deposited by spray pyrolysis in air at moderate temperatures of 350 oC from pentane-2,4-dione solutions of SiCl4. SiO2 dielectrics were investigated by means of UV–Vis absorption spectroscopy, spectroscopic ellipsometry, XPS, XRD, UFM/AFM, admittance spectroscopy, and field-effect measurements. Data analysis reveals smooth (RRMS<1 nm) amorphous films with a dielectric constant of about 3.8, an optical band gap of ≈8.1 eV, leakage current densities in the order of ≈10-7 A/cm2 at 1 MV/cm and high dielectric strength in excess of 5 MV/cm. XPS measurements confirm the SiO2 stoichiometry and FTIR spectra reveal features related to SiO2 only. Thin film transistors implementing spray coated SiO2 gate dielectrics and C60 and pentacene semiconducting channels exhibit excellent transport characteristics i.e. negligible hysteresis, low leakage currents, high on/off current modulation ratio in the order of 106 and high carrier mobility

    Search based software engineering: Trends, techniques and applications

    Get PDF
    © ACM, 2012. This is the author's version of the work. It is posted here by permission of ACM for your personal use. Not for redistribution. The definitive version is available from the link below.In the past five years there has been a dramatic increase in work on Search-Based Software Engineering (SBSE), an approach to Software Engineering (SE) in which Search-Based Optimization (SBO) algorithms are used to address problems in SE. SBSE has been applied to problems throughout the SE lifecycle, from requirements and project planning to maintenance and reengineering. The approach is attractive because it offers a suite of adaptive automated and semiautomated solutions in situations typified by large complex problem spaces with multiple competing and conflicting objectives. This article provides a review and classification of literature on SBSE. The work identifies research trends and relationships between the techniques applied and the applications to which they have been applied and highlights gaps in the literature and avenues for further research.EPSRC and E

    CHESTNUT: Improve serendipity in movie recommendation by an Information Theory-based collaborative filtering approach

    Get PDF
    The term serendipity has been understood narrowly in the Recommender System. Applying a user-centered approach, user-friendly serendipitous recommender systems are expected to be developed based on a good understanding of serendipity. In this paper, we introduce CHESTNUT , a memory-based movie collaborative filtering system to improve serendipity performance. Relying on a proposed Information Theory-based algorithm and previous study, we demonstrate a method of successfully injecting insight, unexpectedness and usefulness, which are key metrics for a more comprehensive understanding of serendipity, into a practical serendipitous runtime system. With lightweight experiments, we have revealed a few runtime issues and further optimized the same. We have evaluated CHESTNUT in both practicability and effectiveness , and the results show that it is fast, scalable and improves serendip-ity performance significantly, compared with mainstream memory-based collaborative filtering. The source codes of CHESTNUT are online at https://github.com/unnc-idl-ucc/CHESTNUT/

    Egg Consumption and Risk of Type 2 Diabetes in Men and Women

    Get PDF
    OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts
    corecore