260 research outputs found

    Konstruktivistische Ansätze in der Erwachsenenbildung und Weiterbildung

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    Theoretical approaches in the field of further education and advanced vocational training have to face multifaceted demands: the analysis of knowledge aquisition and knowledge transfer and its instructional support as well as the revealment of the mechanisms which influence further education on an organisational level in companies. This article describes, that herefore especially moderate constructivistic approaches are useful. After an introduction to the philosophical tradition of these approaches and important characteristics of adult learning, two examples of constructivistic models are being described particularly: The theory of situated learning environments and career counseling. Concluding it is shown, that a moderate constructive perspective fulfils important criteria for the theoretic modelling of further education processes.Theoretische Ansätze in der Erwachsenen- und insbesondere in der beruflichen Weiterbildung müssen sich vielfältigen Ansprüchen stellen: der Analyse des Wissenserwerbs und Wissenstransfers und seiner instruktionalen Unterstützung ebenso wie der Aufdeckung der Mechanismen, die in den Betrieben auf organisatorischer Ebene die Weiterbildung beeinflussen. In diesem Beitrag wird die Auffassung vertreten, daß dafür insbesondere liberalisierte konstruktivistische Ansätze gut geeignet sind. Nach einer Einführung in die philosophische Tradition dieser Ansätze und wichtiger Merkmale des Lernens im Erwachsenenalter werden zwei Beispiele konstruktivistischer Modelle genauer beschrieben: die Theorie situierter Lernumgebungen und das career counseling. Abschließend wird gezeigt, daß eine liberalisierte konstruktivistische Perspektive wichtige Kriterien für die theoretische Modellierung von Weiterbildungsprozessen erfüllt

    Abnormal Frontostriatal Activity During Unexpected Reward Receipt in Depression and Schizophrenia: Relationship to Anhedonia.

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    Alterations in reward processes may underlie motivational and anhedonic symptoms in depression and schizophrenia. However it remains unclear whether these alterations are disorder-specific or shared, and whether they clearly relate to symptom generation or not. We studied brain responses to unexpected rewards during a simulated slot-machine game in 24 patients with depression, 21 patients with schizophrenia, and 21 healthy controls using functional magnetic resonance imaging. We investigated relationships between brain activation, task-related motivation, and questionnaire rated anhedonia. There was reduced activation in the orbitofrontal cortex, ventral striatum, inferior temporal gyrus, and occipital cortex in both depression and schizophrenia in comparison with healthy participants during receipt of unexpected reward. In the medial prefrontal cortex both patient groups showed reduced activation, with activation significantly more abnormal in schizophrenia than depression. Anterior cingulate and medial frontal cortical activation predicted task-related motivation, which in turn predicted anhedonia severity in schizophrenia. Our findings provide evidence for overlapping hypofunction in ventral striatal and orbitofrontal regions in depression and schizophrenia during unexpected reward receipt, and for a relationship between unexpected reward processing in the medial prefrontal cortex and the generation of motivational states.Supported by a MRC Clinician Scientist award (G0701911), a Brain and Behaviour Research Foundation Young Investigator, and an Isaac Newton Trust award to Dr Murray; an award to Dr Segarra from the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the European Union; by the University of Cambridge Behavioural and Clinical Neuroscience Institute, funded by a joint award from the Medical Research Council and Wellcome Trust (G1000183 and 093875/Z/10Z respectively); by awards from the Wellcome Trust (095692) and the Bernard Wolfe Health Neuroscience Fund to Professor Fletcher, and by awards from the Wellcome Trust Institutional Strategic Support Fund (097814/Z/11) and Cambridge NIHR Biomedical Research Centre. The authors are grateful for the help of clinical staff in CAMEO, in the Cambridge Rehabilitation and Recovery service and Pathways, and in the Cambridge IAPT service, for help with participant recruitment.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/npp.2015.37

    Exploring new physics frontiers through numerical relativity

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    The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

    Genetic and pharmacological inhibition of CDK9 drives neutrophil apoptosis to resolve inflammation in zebrafish in vivo

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    Neutrophilic inflammation is tightly regulated and subsequently resolves to limit tissue damage and promote repair. When the timely resolution of inflammation is dysregulated, tissue damage and disease results. One key control mechanism is neutrophil apoptosis, followed by apoptotic cell clearance by phagocytes such as macrophages. Cyclin-dependent kinase (CDK) inhibitor drugs induce neutrophil apoptosis in vitro and promote resolution of inflammation in rodent models. Here we present the first in vivo evidence, using pharmacological and genetic approaches, that CDK9 is involved in the resolution of neutrophil-dependent inflammation. Using live cell imaging in zebrafish with labelled neutrophils and macrophages, we show that pharmacological inhibition, morpholino-mediated knockdown and CRISPR/cas9-mediated knockout of CDK9 enhances inflammation resolution by reducing neutrophil numbers via induction of apoptosis after tailfin injury. Importantly, knockdown of the negative regulator La-related protein 7 (LaRP7) increased neutrophilic inflammation. Our data show that CDK9 is a possible target for controlling resolution of inflammation

    Animated molecular dynamics simulations of hydrated caesium-smectite interlayers

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    Computer animation of center of mass coordinates obtained from 800 ps molecular dynamics simulations of Cs-smectite hydrates (1/3 and 2/3 water monolayers) provided information concerning the structure and dynamics of the interlayer region that could not be obtained through traditional simulation analysis methods. Cs(+ )formed inner sphere complexes with the mineral surface, and could be seen to jump from one attracting location near a layer charge site to the next, while water molecules were observed to migrate from the hydration shell of one ion to that of another. Neighboring ions maintained a partial hydration shell by sharing water molecules, such that a single water molecule hydrated two ions simultaneously for hundreds of picoseconds. Cs-montmorillonite hydrates featured the largest extent of this sharing interaction, because interlayer ions were able to inhabit positions near surface cavities as well as at their edges, close to oxygen triads. The greater positional freedom of Cs(+ )within the montmorillonite interlayer, a result of structural hydroxyl orientation and low tetrahedral charge, promoted the optimization of distances between cations and water molecules required for water sharing. Preference of Cs(+ )for locations near oxygen triads was observed within interlayer beidellite and hectorite. Water molecules also could be seen to interact directly with the mineral surface, entering its surface cavities to approach attracting charge sites and structural hydroxyls. With increasing water content, water molecules exhibited increased frequency and duration of both cavity habitation and water sharing interactions. Competition between Cs(+ )and water molecules for surface sites was evident. These important cooperative and competitive features of interlayer molecular behavior were uniquely revealed by animation of an otherwise highly complex simulation output

    Pathways between Primary Production and Fisheries Yields of Large Marine Ecosystems

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    The shift in marine resource management from a compartmentalized approach of dealing with resources on a species basis to an approach based on management of spatially defined ecosystems requires an accurate accounting of energy flow. The flow of energy from primary production through the food web will ultimately limit upper trophic-level fishery yields. In this work, we examine the relationship between yield and several metrics including net primary production, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production. We also evaluate the relationship between yield and two additional rate measures that describe the export of energy from the pelagic food web, particle export flux and mesozooplankton productivity. We found primary production is a poor predictor of global fishery yields for a sample of 52 large marine ecosystems. However, chlorophyll concentration, particle-export ratio, and the ratio of secondary to primary production were positively associated with yields. The latter two measures provide greater mechanistic insight into factors controlling fishery production than chlorophyll concentration alone. Particle export flux and mesozooplankton productivity were also significantly related to yield on a global basis. Collectively, our analyses suggest that factors related to the export of energy from pelagic food webs are critical to defining patterns of fishery yields. Such trophic patterns are associated with temperature and latitude and hence greater yields are associated with colder, high latitude ecosystems

    Prevention of depression and anxiety in adolescents: A randomized controlled trial testing the efficacy and mechanisms of Internet-based self-help problem-solving therapy

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    <p>Abstract</p> <p>Background</p> <p>Even though depression and anxiety are highly prevalent in adolescence, youngsters are not inclined to seek help in regular healthcare. Therapy through the Internet, however, has been found to appeal strongly to young people. The main aim of the present study is to examine the efficacy of preventive Internet-based guided self-help problem-solving therapy with adolescents reporting depressive and anxiety symptoms. A secondary objective is to test potential mediating and moderating variables in order to gain insight into how the intervention works and for whom it works best.</p> <p>Methods/design</p> <p>This study is a randomized controlled trial with an intervention condition group and a wait-list control group. The intervention condition group receives Internet-based self-help problem-solving therapy. Support is provided by a professional and delivered through email. Participants in the wait-list control group receive the intervention four months later. The study population consists of adolescents (12-18-year-olds) from the general population who report mild to moderate depressive and/or anxiety symptoms and are willing to complete a self-help course. Primary outcomes are symptoms of depression and anxiety. Secondary outcomes are quality of life, social anxiety, and cost-effectiveness. The following variables are examined for their moderating role: demographics, motivation, treatment credibility and expectancy, externalizing behaviour, perceived social support from parents and friends, substance use, the experience of important life events, physical activity, the quality of the therapeutic alliance, and satisfaction. Mediator variables include problem-solving skills, worrying, mastery, and self-esteem. Data are collected at baseline and at 3 weeks, 5 weeks, 4 months, 8 months, and 12 months after baseline. Both intention-to-treat and completer analyses will be conducted.</p> <p>Discussion</p> <p>This study evaluates the efficacy and mechanisms of Internet-based problem-solving therapy for adolescents. If Internet-based problem-solving therapy is shown to reduce depressive and anxiety symptoms in adolescents, the implication is to implement the intervention in clinical practice. Strengths and limitations of the study are discussed.</p> <p>Trial registration</p> <p>Netherlands Trial Register NTR1322</p

    HIV infection and HERV expression: a review

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    The human genome contains multiple copies of retrovirus genomes known as endogenous retroviruses (ERVs) that have entered the germ-line at some point in evolution. Several of these proviruses have retained (partial) coding capacity, so that a number of viral proteins or even virus particles are expressed under various conditions. Human ERVs (HERVs) belong to the beta-, gamma-, or spuma- retrovirus groups. Endogenous delta- and lenti- viruses are notably absent in humans, although endogenous lentivirus genomes have been found in lower primates. Exogenous retroviruses that currently form a health threat to humans intriguingly belong to those absent groups. The best studied of the two infectious human retroviruses is the lentivirus human immunodeficiency virus (HIV) which has an overwhelming influence on its host by infecting cells of the immune system. One HIV-induced change is the induction of HERV transcription, often leading to induced HERV protein expression. This review will discuss the potential HIV-HERV interactions

    Pan-cancer analysis of whole genomes

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    Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe
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