221 research outputs found

    Dynamic subfilter-scale stress model for large-eddy simulations

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    We present a modification of the integral length-scale approximation (ILSA) model originally proposed by Piomelli et al. [Piomelli et al., J. Fluid Mech. 766, 499 (2015)] and apply it to plane channel flow and a backward-facing step. In the ILSA models the length scale is expressed in terms of the integral length scale of turbulence and is determined by the flow characteristics, decoupled from the simulation grid. In the original formulation the model coefficient was constant, determined by requiring a desired global contribution of the unresolved subfilter scales (SFSs) to the dissipation rate, known as SFS activity; its value was found by a set of coarse-grid calculations. Here we develop two modifications. We de-fine a measure of SFS activity (based on turbulent stresses), which adds to the robustness of the model, particularly at high Reynolds numbers, and removes the need for the prior coarse-grid calculations: The model coefficient can be computed dynamically and adapt to large-scale unsteadiness. Furthermore, the desired level of SFS activity is now enforced locally (and not integrated over the entire volume, as in the original model), providing better control over model activity and also improving the near-wall behavior of the model. Application of the local ILSA to channel flow and a backward-facing step and comparison with the original ILSA and with the dynamic model of Germano et al. [Germano et al., Phys. Fluids A 3, 1760 (1991)] show better control over the model contribution in the local ILSA, while the positive properties of the original formulation (including its higher accuracy compared to the dynamic model on coarse grids) are maintained. The backward-facing step also highlights the advantage of the decoupling of the model length scale from the mesh

    Selective labeling: identifying representative sub-volumes for interactive segmentation

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    Automatic segmentation of challenging biomedical volumes with multiple objects is still an open research field. Automatic approaches usually require a large amount of training data to be able to model the complex and often noisy appearance and structure of biological organelles and their boundaries. However, due to the variety of different biological specimens and the large volume sizes of the datasets, training data is costly to produce, error prone and sparsely available. Here, we propose a novel Selective Labeling algorithm to overcome these challenges; an unsupervised sub-volume proposal method that identifies the most representative regions of a volume. This massively-reduced subset of regions are then manually labeled and combined with an active learning procedure to fully segment the volume. Results on a publicly available EM dataset demonstrate the quality of our approach by achieving equivalent segmentation accuracy with only 5 % of the training data

    Brief Report: Inhibitory Control of Socially Relevant Stimuli in Children with High Functioning Autism

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    The current study explored whether inhibitory control deficits in high functioning autism (HFA) emerged when socially relevant stimuli were used and whether arousal level affected the performance. A Go/NoGo paradigm, with socially relevant stimuli and varying presentation rates, was applied in 18 children with HFA (including children with autism or Asperger syndrome) and 22 typically developing children (aged 8–13 years). Children with HFA did not show inhibitory control deficits compared to the control group, but their performance deteriorated in the slow presentation rate condition. Findings were unrelated to children’s abilities to recognize emotions. Hence, rather than a core deficit in inhibitory control, low arousal level in response to social stimuli might influence the responses given by children with HFA

    A Transient Transgenic RNAi Strategy for Rapid Characterization of Gene Function during Embryonic Development

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    RNA interference (RNAi) is a powerful strategy for studying the phenotypic consequences of reduced gene expression levels in model systems. To develop a method for the rapid characterization of the developmental consequences of gene dysregulation, we tested the use of RNAi for “transient transgenic” knockdown of mRNA in mouse embryos. These methods included lentiviral infection as well as transposition using the Sleeping Beauty (SB) and PiggyBac (PB) transposable element systems. This approach can be useful for phenotypic validation of putative mutant loci, as we demonstrate by confirming that knockdown of Prdm16 phenocopies the ENU-induced cleft palate (CP) mutant, csp1. This strategy is attractive as an alternative to gene targeting in embryonic stem cells, as it is simple and yields phenotypic information in a matter of weeks. Of the three methodologies tested, the PB transposon system produced high numbers of transgenic embryos with the expected phenotype, demonstrating its utility as a screening method

    Optogenetic Manipulation of Cerebellar Purkinje Cell Activity In Vivo

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    Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum

    Induction of plasminogen activator inhibitor type-1 (PAI-1) by hypoxia and irradiation in human head and neck carcinoma cell lines

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    Contains fulltext : 53187.pdf ( ) (Open Access)BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) often contain highly radioresistant hypoxic regions, nonetheless, radiotherapy is a common treatment modality for these tumours. Reoxygenation during fractionated radiotherapy is desired to render these hypoxic tumour regions more radiosensitive. Hypoxia additionally leads to up-regulation of PAI-1, a protein involved in tumour progression and an established prognostic marker for poor outcome. However, the impact of reoxygenation and radiation on PAI-1 levels is not yet clear. Therefore, we investigated the kinetics of PAI-1 expression and secretion after hypoxia and reoxygenation, and determined the influence of ionizing radiation on PAI-1 levels in the two human SCCHN cell lines, BHY and FaDu. METHODS: HIF-1alpha immunoblot was used to visualize the degree of hypoxia in the two cell lines. Cellular PAI-1 expression was investigated by immunofluorescence microscopy. ELISA was used to quantify relative changes in PAI-1 expression (cell lysates) and secretion (cell culture supernatants) in response to various lengths (2-4 h) of hypoxic exposure (< 0.66% O2), reoxygenation (24 h, 20% O2), and radiation (0, 2, 5 and 10 Gy). RESULTS: HIF-1alpha expression was induced between 2 and 24 h of hypoxic exposure. Intracellular PAI-1 expression was significantly increased in BHY and FaDu cells as early as 4 h after hypoxic exposure. A significant induction in secreted PAI-1 was seen after 12 to 24 h (BHY) and 8 to 24 h (FaDu) hypoxia, as compared to the normoxic control. A 24 h reoxygenation period caused significantly less PAI-1 secretion than a 24 h hypoxia period in FaDu cells. Irradiation led to an up-regulation of PAI-1 expression and secretion in both, BHY and FaDu cells. CONCLUSION: Our data suggest that both, short-term (approximately 4-8 h) and long-term (approximately 20-24 h) hypoxic exposure could increase PAI-1 levels in SCCHN in vivo. Importantly, radiation itself could lead to PAI-1 up-regulation in head and neck tumours, whereas reoxygenation of hypoxic tumour cells during fractionated radiotherapy could counteract the increased PAI-1 levels

    Occupational stress, work-home interference and burnout among Belgian veterinary practitioners

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    There have been few formal studies on stress in veterinary surgeons and, in the rare studies available, stress is not examined jointly through the levels of job strain and job engagement, the sources of stress in the issue of work environment and the work-home interference. The authors' goal in this study was to analyse job engagement, job strain, burnout, work-home interference and job stress factors among 216 Belgian veterinary surgeons. Rural practice was compared to small animal and mixed activity. The mean job strain and job engagement level in veterinary surgeons was not higher than what we found in other working populations. However, 15.6% of the group were found to be suffering from high burnout. Rural practitioners had a lower level of job engagement than small animal veterinary surgeons. These small animal practitioners had a lower level of job strain than the mixed practitioners. The level of burnout did not differ significantly across the three types of activity. In comparison to other Belgian and Dutch workers, veterinary surgeons perceived more negative work-home interference. Bovine and mixed practitioners were the most concerned with this problem. The two most important sources of stress reported by bovine practitioners were relations to farmers and working time management (including emergencies and availability)
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