Networked experiments and scientific resource sharing in cooperative knowledge spaces

Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugänglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.Cooperative knowledge spaces create new potentials for the experimental fields in natural sciences and engineering because they enhance the accessibility of experimental setups through virtual laboratories and remote technology, opening them for collaborative and distributed usage. A concept for extending existing virtual knowledge spaces for the means of the technological disciplines (“ViCToR‐Spaces” ‐ Virtual Cooperation in Teaching and Research for Mathematics, Natural Sciences and Engineering) is presented. The integration of networked virtual laboratories and remote experiments (“NanoLab Approach”), as well as an approach to community‐driven content sharing and content development within virtual knowledge spaces (NanoWiki) are described

Post-translational derepression of invertase activity in source leaves via down-regulation of invertase inhibitor expression is part of the plant defense response

There is increasing evidence that pathogens do not only elicit direct defense responses, but also cause pronounced changes in primary carbohydrate metabolism. Cell-wall-bound invertases belong to the key regulators of carbohydrate partitioning and source-sink relations. Whereas studies have focused so far only on the transcriptional induction of invertase genes in response to pathogen infection, the role of post-translational regulation of invertase activity has been neglected and was the focus of the present study. Expression analyses revealed that the high mRNA level of one out of three proteinaceous invertase inhibitors in source leaves of Arabidopsis thaliana is strongly repressed upon infection by a virulent strain of Pseudomonas syringae pv. tomato DC3000. This repression is paralleled by a decrease in invertase inhibitor activity. The physiological role of this regulatory mechanism is revealed by the finding that in situ invertase activity was detectable only upon infection by P. syringae. In contrast, a high invertase activity could be measured in vitro in crude and cell wall extracts prepared from both infected and non-infected leaves. The discrepancy between the in situ and in vitro invertase activity of control leaves and the high in situ invertase activity in infected leaves can be explained by the pathogen-dependent repression of invertase inhibitor expression and a concomitant reduction in invertase inhibitor activity. The functional importance of the release of invertase from post-translational inhibition for the defense response was substantiated by the application of the competitive chemical invertase inhibitor acarbose. Post-translational inhibition of extracellular invertase activity by infiltration of acarbose in leaves was shown to increase the susceptibility to P. syringae. The impact of invertase inhibition on spatial and temporal dynamics of the repression of photosynthesis and promotion of bacterial growth during pathogen infection supports a role for extracellular invertase in plant defense. The acarbose-mediated increase in susceptibility was also detectable in sid2 and cpr6 mutants and resulted in slightly elevated levels of salicylic acid, demonstrating that the effect is independent of the salicylic acid-regulated defense pathway. These findings provide an explanation for high extractable invertase activity found in source leaves that is kept inhibited in situ by post-translational interaction between invertase and the invertase inhibitor proteins. Upon pathogen infection, the invertase activity is released by repression of invertase inhibitor expression, thus linking the local induction of sink strength to the plant defense response

A photoinduced pH jump applied to drug release from cucurbit[7]uril

A proof-of-principle for the application of a photoinduced pH jump for delivery of the Hoechst 33258 drug by disassembly of its host-guest complex with cucurbit[7]uril is described

CSMET: Comparative Genomic Motif Detection via Multi-Resolution Phylogenetic Shadowing

Functional turnover of transcription factor binding sites (TFBSs), such as whole-motif loss or gain, are common events during genome evolution. Conventional probabilistic phylogenetic shadowing methods model the evolution of genomes only at nucleotide level, and lack the ability to capture the evolutionary dynamics of functional turnover of aligned sequence entities. As a result, comparative genomic search of non-conserved motifs across evolutionarily related taxa remains a difficult challenge, especially in higher eukaryotes, where the cis-regulatory regions containing motifs can be long and divergent; existing methods rely heavily on specialized pattern-driven heuristic search or sampling algorithms, which can be difficult to generalize and hard to interpret based on phylogenetic principles. We propose a new method: Conditional Shadowing via Multi-resolution Evolutionary Trees, or CSMET, which uses a context-dependent probabilistic graphical model that allows aligned sites from different taxa in a multiple alignment to be modeled by either a background or an appropriate motif phylogeny conditioning on the functional specifications of each taxon. The functional specifications themselves are the output of a phylogeny which models the evolution not of individual nucleotides, but of the overall functionality (e.g., functional retention or loss) of the aligned sequence segments over lineages. Combining this method with a hidden Markov model that autocorrelates evolutionary rates on successive sites in the genome, CSMET offers a principled way to take into consideration lineage-specific evolution of TFBSs during motif detection, and a readily computable analytical form of the posterior distribution of motifs under TFBS turnover. On both simulated and real Drosophila cis-regulatory modules, CSMET outperforms other state-of-the-art comparative genomic motif finders

Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences

Risk governance in organizations

Dieses Buch dokumentiert 10 Jahre Risk-Governance-Forschung an der Universität Siegen. In 50 Beiträgen reflektieren Forscher und Praktiker Risk Governance vor dem Hintergrund ihrer eigenen Forschungen und/oder Erfahrungen und geben jeweils einen Entwicklungsimpuls für die Zukunft der Risk Governance. Das Buch zeigt die große Bandbreite und Tiefe des Forschungsgebietes auf und diskutiert Grundannahmen, Implementierungsfragen, die Rolle der Risk Governance als Transformationsmotor, ihre Wirkung in den verschiedenen betrieblichen Funktionen, Entwicklungsperspektiven und den Beitrag der Risk Governance zu einer nachhaltigen Ausrichtung von Unternehmen.This book documents 10 years of risk governance research at the University of Siegen. In 50 contributions, researchers and practitioners reflect on risk governance against the background of their own research and/or experience and provide a development impetus for the future of risk governance. The book shows the wide range and depth of the research field and discusses basic assumptions, implementation issues, the role of risk governance as transformation engine, its impact in the various operational functions, development perspectives, and the contribution of risk governance to a sustainable orientation of companies

Genetic Determinants of Serum Testosterone Concentrations in Men

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterone's high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBG's affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation

Azimuthal anisotropy of charged jet production in root s(NN)=2.76 TeV Pb-Pb collisions

We present measurements of the azimuthal dependence of charged jet production in central and semi-central root s(NN) = 2.76 TeV Pb-Pb collisions with respect to the second harmonic event plane, quantified as nu(ch)(2) (jet). Jet finding is performed employing the anti-k(T) algorithm with a resolution parameter R = 0.2 using charged tracks from the ALICE tracking system. The contribution of the azimuthal anisotropy of the underlying event is taken into account event-by-event. The remaining (statistical) region-to-region fluctuations are removed on an ensemble basis by unfolding the jet spectra for different event plane orientations independently. Significant non-zero nu(ch)(2) (jet) is observed in semi-central collisions (30-50% centrality) for 20 <p(T)(ch) (jet) <90 GeV/c. The azimuthal dependence of the charged jet production is similar to the dependence observed for jets comprising both charged and neutral fragments, and compatible with measurements of the nu(2) of single charged particles at high p(T). Good agreement between the data and predictions from JEWEL, an event generator simulating parton shower evolution in the presence of a dense QCD medium, is found in semi-central collisions. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Forward-central two-particle correlations in p-Pb collisions at root s(NN)=5.02 TeV

Two-particle angular correlations between trigger particles in the forward pseudorapidity range (2.5 2GeV/c. (C) 2015 CERN for the benefit of the ALICE Collaboration. Published by Elsevier B. V.Peer reviewe