1,656 research outputs found

    Transgenic inhibition of neuronal calcineurin activity in the forebrain facilitates fear conditioning, but inhibits the extinction of contextual fear memories

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    It is unclear whether protein phosphatases, which counteract the actions of protein kinases, play a beneficial role in the formation and extinction of previously acquired fear memories. In this study, we investigated the role of the calcium/calmodulin dependent phosphatase 2B, also known as calcineurin (CaN) in the formation of contextual fear memory and extinction of previously acquired contextual fear. We used a temporally regulated transgenic approach, that allowed us to selectively inhibit neuronal CaN activity in the forebrain either during conditioning or only during extinction training leaving the conditioning undisturbed. Reducing CaN activity through the expression of a CaN inhibitor facilitated contextual fear conditioning, while it impaired the extinction of previously formed contextual fear memory. These findings give the first genetic evidence that neuronal CaN plays an opposite role in the formation of contextual fear memories and the extinction of previously formed contextual fear memories. (C) 2007 Elsevier Inc. All rights reserved

    Гарантоздатність як фундаментальний узагальнюючий та інтегруючий підхід

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    Представлені головні принципи та умови становлення і етапи розвитку фундаментальної теорії і практики узагальнюючих та інтегруючих концепцій гарантоздатності, починаючи з першої об’єднаної конференції двох наукових шкіл Дж. фон Неймана і Н. Вінера. Приведені основні положення розвитку теоретичних засад і результатів прикладних досліджень інтеграційних процесів безвідмовності (надійності), відмовостійкості та гарантоздатності інформаційно-управляючих комп’ютерних систем (ІУКС).Представлены главные принципы, условия становления и этапы развития фундаментальной теории и практики обобщающих и интегрирующих концепций гарантоспособности, начиная с первой объединённой конференции двух научных школ Дж. фон Неймана и Н. Винера. Приведены основные положения развития теоретических основ и результатов прикладных исследований интеграционных процессов безотказности (надёжности), отказоустойчивости и гарантоспособности информационно-управляющих компьютерных систем (ИУКС).The main principles and conditions of formation and stages of development of the fundamental theory and practice of the generalizing and integrating concepts of dependability were presented after the leadthrough the first joint conference of two scientific schools of J. von Neumann and N. Wiener. The basic aspects of development of theoretical principles and results of applied researches of integration processes of reliability (fail-safety)

    Phenotype standardization for statin-induced myotoxicity

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    Statins are widely used lipid-lowering drugs that are effective in reducing cardiovascular disease risk. Although they are generally well tolerated, they can cause muscle toxicity, which can lead to severe rhabdomyolysis. Research in this area has been hampered to some extent by the lack of standardized nomenclature and phenotypic definitions. We have used numerical and descriptive classifications and developed an algorithm to define statin-related myotoxicity phenotypes, including myalgia, myopathy, rhabdomyolysis, and necrotizing autoimmune myopathy.</p

    Multicultural personality and effectiveness in an intercultural training simulation: The role of stress and pro‐active communication

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    Multicultural personality traits have been shown to predict intercultural outcomes in a range of settings. However, how these traits affect behaviour during intercultural interactions remains an understudied area. A study was conducted among participants in intercultural training sessions, to examine whether scores on the five dimensions of the Multicultural Personality Questionnaire (MPQ) could predict how they performed in the intercultural simulation game “Barnga.” Both a self-rating and other-rating of intercultural effectiveness were included. Furthermore, we examined whether perceived stress and pro-active communication played a mediating role. Results of Latent Growth Curve Modelling (LGCM) show that emotional stability has a positive effect on mean scores (intercept) of both self-rated and other-rated outcomes, mediated through perceived stress. Social Initiative has a positive effect on the rate of improvement (slope) in other-rated outcomes during the simulation, mediated through pro-active communication

    The effects of social environment on AD-related pathology in hAPP-J20 mice and tau-P301L mice

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    In humans, social factors (e.g., loneliness) have been linked to the risk of developing Alzheimer's Disease (AD). To date, AD pathology is primarily characterized by amyloid-β plaques and tau tangles. We aimed to assess the effect of single- and group-housing on AD-related pathology in a mouse model for amyloid pathology (J20, and WT controls) and a mouse model for tau pathology (P301L) with and without seeding of synthetic human tau fragments (K18). Female mice were either single housed (SH) or group housed (GH) from the age of 6-7 weeks onwards. In 12-week-old P301L mice, tau pathology was induced through seeding by injecting K18 into the dorsal hippocampus (P301L K18), while control mice received a PBS injection (P301L PBS). P301L mice were sacrificed at 4 months of age and J20 mice at 10 months of age. In all mice brain pathology was histologically assessed by examining microglia, the CA1 pyramidal cell layer and specific AD pathology: analysis of plaques in J20 mice and tau hyperphosphorylation in P301L mice. Contrary to our expectation, SH-J20 mice interestingly displayed fewer plaques in the hippocampus compared to GH-J20 mice. However, housing did not affect tau hyperphosphorylation at Ser202/Thr205 of P301L mice, nor neuronal cell death in the CA1 region in any of the mice. The number of microglia was increased by the J20 genotype, and their activation (based on cell body to cell size ratio) in the CA1 was affected by genotype and housing condition (interaction effect). Single housing of P301L mice was linked to the development of stereotypic behavior (i.e. somersaulting and circling behavior). In P301L K18 mice, an increased number of microglia were observed, among which were rod microglia. Taken together, our findings point to a significant effect of social housing conditions on amyloid plaques and microglia in J20 mice and on the development of stereotypic behavior in P301L mice, indicating that the social environment can modulate AD-related pathology. </p

    Results of international standardised beekeeper surveys of colony losses for winter 2012-2013 : analysis of winter loss rates and mixed effects modelling of risk factors for winter loss.

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    This article presents results of an analysis of winter losses of honey bee colonies from 19 mainly European countries, most of which implemented the standardised 2013 COLOSS questionnaire. Generalised linear mixed effects models (GLMMs) were used to investigate the effects of several factors on the risk of colony loss, including different treatments for Varroa destructor, allowing for random effects of beekeeper and region. Both winter and summer treatments were considered, and the most common combinations of treatment and timing were used to define treatment factor levels. Overall and within country colony loss rates are presented. Significant factors in the model were found to be: percentage of young queens in the colonies before winter, extent of queen problems in summer, treatment of the varroa mite, and access by foraging honey bees to oilseed rape and maize. Spatial variation at the beekeeper level is shown across geographical regions using random effects from the fitted models, both before and after allowing for the effect of the significant terms in the model. This spatial variation is considerable

    Biological decolorization of xanthene dyes by anaerobic granular biomass

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    Biodegradation of a xanthene dyes was investigated for the first time using anaerobic granular sludge. On a first screening, biomass was able to decolorize, at different extents, six azo dye solutions: acid orange 7, direct black 19, direct blue 71, mordant yellow 10, reactive red 2 and reactive red 120 and two xanthene dyes—Erythrosine B and Eosin Y. Biomass concentration, type of electron donor, induction of biomass with dye and mediation with activated carbon (AC) were variables studied for Erythrosine B (Ery) as model dye. Maximum color removal efficiency was achieved with 4.71 g VSS L−1, while the process rates were independent of the biomass concentration above 1.89 g VSS L−1. No considerable effects were observed when different substrates were used as electron donors (VFA, glucose or lactose). Addition of Ery in the incubation period of biomass led to a fivefold increase of the decolorization rate. The rate of Ery decolorization almost duplicated in the presence of commercial AC (0.1 g L−1 AC0). Using different modified AC samples (from the treatment of AC0), a threefold higher rate was obtained with the most basic one, \textAC\textH2ACH2, as compared with non-mediated reaction. Higher rates were obtained at pH 6.0. Chemical reduction using Na2S confirmed the recalcitrant nature of this dye. The results attest that decolorization of Ery is essentially due to enzymatic and adsorption phenomena.This work was supported by the PTDC/AMB/69335/2006 project grants (Fundacao para a Ciencia e Technologia, FCT, Portugal), BRAIN project (ID 6681, European Social Found and Romanian Government and the grant of the Romanian National Authority for Scientific Research, CNCS-UEFISCDI, project number PN-II-ID-PCE-2011-3-0559, Contract 265/2011

    Supporting Self-Regulated Learning in Online Learning Environments and MOOCs: A Systematic Review

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    Massive Open Online Courses (MOOCs) allow learning to take place anytime and anywhere with little external monitoring by teachers. Characteristically, highly diverse groups of learners enrolled in MOOCs are required to make decisions related to their own learning activities to achieve academic success. Therefore, it is considered important to support self-regulated learning (SRL) strategies and adapt to relevant human factors (e.g., gender, cognitive abilities, prior knowledge). SRL supports have been widely investigated in traditional classroom settings, but little is known about how SRL can be supported in MOOCs. Very few experimental studies have been conducted in MOOCs at present. To fill this gap, this paper presents a systematic review of studies on approaches to support SRL in multiple types of online learning environments and how they address human factors. The 35 studies reviewed show that human factors play an important role in the efficacy of SRL supports. Future studies can use learning analytics to understand learners at a fine-grained level to provide support that best fits individual learners. The objective of the paper is twofold: (a) to inform researchers, designers and teachers about the state of the art of SRL support in online learning environments and MOOCs; (b) to provide suggestions for adaptive self-regulated learning support.Teaching and Teacher Learning (ICLON

    Gender shift in realisation of preferred type of gp practice: longitudinal survey over the last 25 years

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    <p>Abstract</p> <p>Background</p> <p>An increasing number of newly trained Dutch GPs prefer to work in a group practice and as a non-principal rather than in a single-handed practice. In view of the greater number of female doctors, changing practice preferences, and discussions on future workforce problems, the question is whether male and female GPs were able to realise their initial preferences in the past and will be able to do so in the future.</p> <p>Methods</p> <p>We have conducted longitudinal cohort study of all GPs in the Netherlands seeking a practice between 1980 and 2004. The Netherlands Institute of Health Services Research (NIVEL) in Utrecht collected the data used in this study by means of a postal questionnaire. The overall mean response rate was 94%.</p> <p>Results</p> <p>Over the past 20 years, an increasing proportion of GPs, both male and female, were able to achieve their preference for working in a group practice and/or in a non-principal position. Relatively more women than men have settled in group practices, and more men than women in single-handed practices; however, the practice preference of men and women is beginning to converge. Dropout was highest among the GPs without any specific practice preference.</p> <p>Conclusion</p> <p>The overwhelming preference of male and female GPs for working in group practices is apparently being met by the number of positions (principal or non-principal) available in group practices. The preference of male and female GPs regarding the type of practice and job conditions is expected to converge further in the near future.</p
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