587 research outputs found

    Transverse instability of gravity–capillary solitary waves on deep water in the presence of constant vorticity

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    Effects of Nerve Growth Factor and Nitric Oxide Synthase Inhibitors on Amyloid Precursor Protein mRNA Levels and Protein Stability

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    We determined previously that nitric oxide (NO) modulates the nerve growth factor (NGF)-mediated increases in amyloid precursor protein (APP) levels in PC12 cells. To elucidate potential mechanisms, the effects of NGF and NO synthase (NOS) inhibitors on APP mRNA levels and protein stability were evaluated. Surprisingly, treatment of PC12 cells with NGF resulted in decreased levels of APP695 and APP751/770 mRNA. Therefore, the effect of NGF on APP protein stability was examined using the translation inhibitor, cycloheximide. Under these conditions, NGF did not alter the rate of APP degradation, suggesting that NGF may be enhancing the translation rate of APP. Since NOS inhibitors attenuate the NGF-mediated increase in APP levels, their effect on APP mRNA levels and protein stability was also assessed. S-methylisothiourea (S-MIU), selective for inducible NOS, decreased both APP695 and APP751/770 mRNA levels while the non-selective NOS inhibitor, Nω-nitro-L-arginine methylester (L-NAME) had no effect. In both control and NGF-treated PC12 cells, S-MIU increased the half-life of APP, with the greatest effect observed with the APP695 isoform. Based on these data we propose that in PC12 cells, NGF increases APP levels through enhanced translation rate and that NO, which modulates the NGF-induced increase in APP protein, also regulates APP mRNA levels and could play a role in APP processing

    Bayesian optimization of the PC algorithm for learning Gaussian Bayesian networks

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    The PC algorithm is a popular method for learning the structure of Gaussian Bayesian networks. It carries out statistical tests to determine absent edges in the network. It is hence governed by two parameters: (i) The type of test, and (ii) its significance level. These parameters are usually set to values recommended by an expert. Nevertheless, such an approach can suffer from human bias, leading to suboptimal reconstruction results. In this paper we consider a more principled approach for choosing these parameters in an automatic way. For this we optimize a reconstruction score evaluated on a set of different Gaussian Bayesian networks. This objective is expensive to evaluate and lacks a closed-form expression, which means that Bayesian optimization (BO) is a natural choice. BO methods use a model to guide the search and are hence able to exploit smoothness properties of the objective surface. We show that the parameters found by a BO method outperform those found by a random search strategy and the expert recommendation. Importantly, we have found that an often overlooked statistical test provides the best over-all reconstruction results

    EC03-1568 Grasshopper Identification Guide for Rangeland and Pasture Summer Feeding Species

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    Many kinds of summer-feeding grasshoppers are found in Nebraska rangeland and pastures. Of these, the six species listed in this guide are most likely to be numerous during outbreak years. These species overwinter as eggs and hatch through much of May and June. When abundant they can cause severe damage to rangeland and pastures, especially when dry conditions limit grass growth. Identification of the species present is important because some have greater potential for damage than others

    Experimental identification and validation of models in micro and macro plasticity

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    For micro-macro approaches to finite plasticity, one needs experimental results on both scales, the engineering scale (macro scale) and the crystal scale (micro scale). Since we know that a monocrystal behaves different from a crystallite embedded in a polycrystal, one is also interested in data obtained on the micro scale of a polycrystal. Such data is needed not only for the identification of the material parameters like hardening variables, but also for the validation of these models. In this paper, experiments on both scales and, in parallel, FEM-simulations are presented, in order to compare the results of both approaches. The specimens stem from a rolled sheet of the deep-drawing steel DC04. On the micro scale indenter tests have been performed and the orientation changes in the volume below the indent have been measured using micron-resolution 3D x-ray microscopy (Larson et al., 2004, 2008). On the macro scale the usual tension tests and additional shear tests in different directions (Bouvier etal.,2006) have been performed. In corresponding simulations, the micro-macro transition is performed by a full constrained Taylor-model and, in order to overcome the drawbacks of the Taylor-model, the RVE technique has been applied

    Membrane-transferring regions of gp41 as targets for HIV-1 fusion inhibition and viral neutralization

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    12 páginas, 4 figurasThe fusogenic function of HIV-1 gp41 transmembrane Env subunit relies on two different kinds of structural elements: i) a collapsible ectodomain structure (the hairpin or six-helix bundle) that opens and closes, and ii) two membrane- transferring regions (MTRs), the fusion peptide (FP) and the membrane-proximal external region (MPER), which ensure coupling of hairpin closure to apposition and fusion of cell and viral membranes. The isolation of naturally produced short peptides and neutralizing IgG-s, that interact with FP and MPER, respectively, and block viral infection, suggests that these conserved regions might represent useful targets for clinical intervention. Furthermore, MTR-derived peptides have been shown to be membrane-active. Here, it is discussed the potential use of these molecules and how the analysis of their membrane activity in vitro could contribute to the development of HIV fusion inhibitors and effective immunogensThe authors wish to thank financial support obtained from Spanish MICINN (BIO2008- 00772) (JLN) and University of the Basque Country (GIU 06/42 and DIPE08/12) (NH and JLN).Peer reviewe

    Corticosteroid status influences the volume of the rat cingulate cortex: a magnetic resonance imaging study

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    Imbalances in the corticosteroid milieu result in reductions in hippocampal volume in humans and experimental rodents. The functional correlates of these changes include deficits in cognitive performance and regulation of the hypothalamic–pituitary–adrenal axis. Since other limbic structures which are intricately connected with the hippocampal formation, also play an important role in behavioural and neuroendocrine functions, we here used magnetic resonance imaging (MRI) to analyse how two of these areas, the anterior cingulate and retrosplenial cortex, respond to chronic alterations of adrenocortical status: hypocortisolism (induced by adrenalectomy, ADX), normocortisolism (ADX with low-dose corticosterone replacement), and hypercortisolism (ADX with high-dose dexamethasone supplementation). Hypercortisolism was associated with a significant reduction in the volume (absolute and normalized) of the left anterior cingulate gyrus as measured by MRI and confirmed using classical histological methods; a similar trend was observed in the right anterior cingulate region. In contrast, hypercortisolism did not influence the volume of the adjacent retrosplenial cortex. The volumes of the anterior cingulate gyrus and retrosplenial cortex were unaffected by the absence of adrenocortical hormones. These findings are the first to suggest that corticosteroid influences on the structure of the limbic system extend beyond the hippocampal formation, i.e., to fronto-limbic areas also

    Hospital variation in missed nursing care

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    Quality of nursing care across hospitals is variable, and this variation can result in poor patient outcomes. One aspect of quality nursing care is the amount of necessary care that is omitted. This article reports on the extent and type of nursing care missed and the reasons for missed care. The MISSCARE Survey was administered to nursing staff (n = 4086) who provide direct patient care in 10 acute care hospitals. Missed nursing care patterns as well as reasons for missing care (labor resources, material resources, and communication) were common across all hospitals. Job title (ie, registered nurse vs nursing assistant), shift worked, absenteeism, perceived staffing adequacy, and patient work loads were significantly associated with missed care. The data from this study can inform quality improvement efforts to reduce missed nursing care and promote favorable patient outcomes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94115/1/Hospital variation in missed nursing care.pd
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