16 research outputs found

    Das digitale Ich. Zwischen Gemeinschaft und Abgrenzung - drei Fallstudien

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    Dieses E-Book enthält drei sozialwissenschaftliche Fallstudien, die Studierende der Hochschule der Medien Stuttgart im Wintersemester 2015/16 in einem Master-Kurs erstellt haben. Die Projekte behandelten neue Trends in der zunehmend digitalisierten Gesellschaft. Thematisch umfassen die drei Teilstudien das "Vertrauen in der Sharing Economy", die "digitale Diaspora" am Beispiel polnischstämmiger Migranten und die "Ethik der Privatheit"

    Genomic Relationships, Novel Loci, and Pleiotropic Mechanisms across Eight Psychiatric Disorders

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    Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.Peer reviewe

    The transcriptional landscape of age in human peripheral blood

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    Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 individuals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the 'transcriptomic age' of an individual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.Peer reviewe

    RNA helicase retinoic acid-inducible gene I as a sensor of Hantaan virus replication

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    Hantaan virus (HTNV) causes severe human disease. The HTNV genome consists of three ssRNA segments of negative polarity that are complexed with viral nucleocapsid (N) protein. How the human innate immune system detects HTNV is unclear. RNA helicase retinoic acid-inducible gene I (RIG-I) does not sense genomic HTNV RNA. So far it has not been analysed whether pathogen-associated molecular patterns generated during the HTNV replication trigger RIG-I-mediated innate responses. Indeed, we found that knock-down of RIG-I in A549 cells, an alveolar epithelial cell line, increases HTNV replication and prevents induction of 2',5'-oligoadenylate synthetase, an interferon-stimulated gene. Moreover, overexpression of wild-type or constitutive active RIG-I in Huh7.5 cells lacking a functional RIG-I diminished HTNV virion production. Intriguingly, reporter assays revealed that in vitro-transcribed HTNV N RNA and expression of the HTNV N ORF triggers RIG-I signalling. This effect was completely blocked by the RNA-binding domain of vaccinia virus E3 protein, suggesting that dsRNA-like secondary structures of HTNV N RNA stimulate RIG-I. Finally, transfection of HTNV N RNA into A549 cells resulted in a 2 log-reduction of viral titres upon challenge with virus. Our study is the first demonstration that RIG-I mediates antiviral innate responses induced by HTNV N RNA during HTNV replication and interferes with HTNV growth

    On the time transformation of mixed integer optimal control problems using a consistent fixed integer control function

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    Nonlinear control systems with instantly changing dynamical behavior can be modeled by introducing an additional control function that is integer valued in contrast to a control function that is allowed to have continuous values. The discretization of a mixed integer optimal control problem (MIOCP) leads to a non differentiable optimization problem and the non differentiability is caused by the integer values. The paper is about a time transformation method that is used to transform a MIOCP with integer dependent constraints into an ordinary optimal control problem. Differentiability is achieved by replacing a variable integer control function with a fixed integer control function and a variable time allows to change the sequence of active integer values. In contrast to other contributions, so called control consistent fixed integer control functions are taken into account here. It is shown that these control consistent fixed integer control functions allow a better accuracy in the resulting trajectories, in particular in the computed switching times. The method is verified on analytical and numerical examples
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