400 research outputs found

    SVD-phy : improved prediction of protein functional associations through singular value decomposition of phylogenetic profiles

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    A successful approach for predicting functional associations between non-homologous genes is to compare their phylogenetic distributions. We have devised a phylogenetic profiling algorithm, SVD-Phy, which uses truncated singular value decomposition to address the problem of uninformative profiles giving rise to false positive predictions. Benchmarking the algorithm against the KEGG pathway database, we found that it has substantially improved performance over existing phylogenetic profiling methods

    Deep cerebral venous sinus thrombosis often presents with neuropsychologic symptoms

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    The outcome of cerebral venous sinus thrombosis (CVST) depends on rapid diagnosis and initiation of effective anticoagulation. We report seven cases of a subgroup with deep cerebral venous sinus thrombosis (DCVST) treated in our institution since 1990. Six of our seven patients presented with early neuropsychological deficits (mental obtundation, bradyphrenia or apathia). This clinical presentation, in combination with headache, and focal neurological deficits, aids the early diagnosis of DCVST. Thalamic hyperintensities on T2-weighted MRI images, previously considered infarctions, were fully reversible during treatment with heparin. This indicates that early in the course of the disease they correspond to vasogenic oedema. (C) 2003 Elsevier Science Ltd. All rights reserved

    Persisting Viral Sequences Shape Microbial CRISPR-Based Immunity

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    Well-studied innate immune systems exist throughout bacteria and archaea, but a more recently discovered genomic locus may offer prokaryotes surprising immunological adaptability. Mediated by a cassette-like genomic locus termed Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), the microbial adaptive immune system differs from its eukaryotic immune analogues by incorporating new immunities unidirectionally. CRISPR thus stores genomically recoverable timelines of virus-host coevolution in natural organisms refractory to laboratory cultivation. Here we combined a population genetic mathematical model of CRISPR-virus coevolution with six years of metagenomic sequencing to link the recoverable genomic dynamics of CRISPR loci to the unknown population dynamics of virus and host in natural communities. Metagenomic reconstructions in an acid-mine drainage system document CRISPR loci conserving ancestral immune elements to the base-pair across thousands of microbial generations. This ‘trailer-end conservation’ occurs despite rapid viral mutation and despite rapid prokaryotic genomic deletion. The trailer-ends of many reconstructed CRISPR loci are also largely identical across a population. ‘Trailer-end clonality’ occurs despite predictions of host immunological diversity due to negative frequency dependent selection (kill the winner dynamics). Statistical clustering and model simulations explain this lack of diversity by capturing rapid selective sweeps by highly immune CRISPR lineages. Potentially explaining ‘trailer-end conservation,’ we record the first example of a viral bloom overwhelming a CRISPR system. The polyclonal viruses bloom even though they share sequences previously targeted by host CRISPR loci. Simulations show how increasing random genomic deletions in CRISPR loci purges immunological controls on long-lived viral sequences, allowing polyclonal viruses to bloom and depressing host fitness. Our results thus link documented patterns of genomic conservation in CRISPR loci to an evolutionary advantage against persistent viruses. By maintaining old immunities, selection may be tuning CRISPR-mediated immunity against viruses reemerging from lysogeny or migration.Version of Recor

    The course of research into the economic consequences of German works councils

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    In a recent survey, Frege (2002) concludes that economic analysis of the works council has reached a `dead end´. The present treatment offers a different conclusion based on a more encompassing review of the evidence. It will identify three distinct phases in the economic analysis of codetermination at the workplace. While Frege just considered studies from the first two phases, it is the third phase of research that contains some of the most positive evaluations to date of works council impact. Even if such estimates appear much exaggerated and the effect of works councils is likely to be small on average, the new literature redirects our research effort towards the factors that produce swings around this average, including differences in works council types and their workplace environments. -- In einem jüngst veröffentlichten Überblicksartikel kommt Frege (2002) zu dem Schluss, die ökonomische Analyse des Betriebsrats sei in eine Sackgasse geraten. Die vorliegende Arbeit zieht ein anderes Fazit, das auf einer umfassenderen Betrachtung der empirischen Evidenz beruht. Dabei werden drei Phasen der ökonomischen Analyse der betrieblichen Mitbestimmung unterschieden. Während Frege nur Studien aus den ersten beiden Phasen berücksichtigte, ist es gerade die dritte Forschungsphase, die einige der positivsten Bewertungen von Betriebsräten enthält. Selbst wenn derartige Einschätzungen stark übertrieben erscheinen und der Betriebsratseffekt im Durchschnitt relativ gering sein dürfte, weist die neuere Literatur darauf hin, dass unsere Forschungsbemühungen sich stärker auf Faktoren konzentrieren sollten, die Schwankungen um diesen Durchschnitt hervorrufen (wie z.B. unterschiedliche Typen von Betriebsräten und deren Arbeitsplatzumgebung).Works council,codetermination,Germany

    German works councils in the production process

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    We estimate the effects of works councils on productivity, 1997-2000, using the IAB Establishment Panel, a nationally representative German data set. We recoup the works council effect by estimating translog production functions, stochastic frontier production functions, and a model in first differences. Once we focus on a core sample of establishments with 21 to 100 employees in which the powers of the works council are a datum, it emerges that the positive productivity differential found in recent studies is a chimera. By the same token, neither is the works council effect negative. This result is important in its own right given the sharply opposing findings of past empirical research and the partisan positions these have helped sustain. -- Anhand des IAB-Betriebspanels, eines repräsentativen deutschen Firmendatensatzes, schätzen wir die Produktivitätswirkungen von Betriebsräten für den Zeitraum 1997-2000. Wir ermitteln den Betriebsratseffekt durch Schätzung von Translog-Produktionsfunktionen und Modellen in ersten Differenzen sowie durch stochastische Produktionsrandschätzungen. Wenn wir uns auf eine Kernstichprobe von Betrieben mit 21 bis 100 Beschäftigten konzentrieren, innerhalb derer die Rechte des Betriebsrats sich nicht ändern, erweist sich das in jüngeren Studien gefundene positive Produktivitätsdifferenzial als Chimäre. Allerdings fällt der Betriebsratseffekt auch nicht negativ aus. Diese Erkenntnis ist angesichts der extrem gegensätzlichen Ergebnisse früherer Studien und der darauf aufbauenden konträren Positionen besonders wichtig.Works council,production functions,panel data,Germany

    Experimental Pneumococcal Meningitis: Impaired Clearance of Bacteria from the Blood Due to Increased Apoptosis in the Spleen in Bcl-2-Deficient Mice

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    Necrotic and apoptotic neuronal cell death can be found in pneumococcal meningitis. We investigated the role of Bcl-2 as an antiapoptotic gene product in pneumococcal meningitis using Bcl-2 knockout (Bcl-2(-/-)) mice. By using a model of pneumococcal meningitis induced by intracerebral infection, Bcl-2-deficient mice and control littermates were assessed by clinical score and a tight rope test at 0, 12, 24, 32, and 36 h after infection. Then mice were sacrificed, the bacterial titers in blood, spleen, and cerebellar homogenates were determined, and the brain and spleen were evaluated histologically. The Bcl-2-deficient mice developed. more severe clinical illness, and there were significant differences in the clinical score at 24, 32, and 36 h and in the tight rope test at 12 and 32 h. The bacterial titers in the blood were greater in Bcl-2-deficient mice than in the controls (7.46 +/- 1.93 log CFU/ml versus 5.16 +/- 0.96 log CFU/ml [mean +/- standard deviation]; P < 0.01). Neuronal damage was most prominent in the hippocampal formation, but there were no significant differences between groups. In situ tailing revealed only a few apoptotic neurons in the brain. In the spleen, however, there were significantly more apoptotic leukocytes in Bcl-2-deficient mice than in controls (5,148 +/- 3,406 leakocytes/mm(2) versus 1,070 +/- 395 leukocytes/mm(2); p < 0.005). Bcl-2 appears to counteract sepsis-induced apoptosis of splenic lymphocytes, thereby enhancing clearance of bacteria from the blood

    HPC-CLUST: distributed hierarchical clustering for large sets of nucleotide sequences

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    MOTIVATION: Nucleotide sequence data are being produced at an ever increasing rate. Clustering such sequences by similarity is often an essential first step in their analysis-intended to reduce redundancy, define gene families or suggest taxonomic units. Exact clustering algorithms, such as hierarchical clustering, scale relatively poorly in terms of run time and memory usage, yet they are desirable because heuristic shortcuts taken during clustering might have unintended consequences in later analysis steps. RESULTS: Here we present HPC-CLUST, a highly optimized software pipeline that can cluster large numbers of pre-aligned DNA sequences by running on distributed computing hardware. It allocates both memory and computing resources efficiently, and can process more than a million sequences in a few hours on a small cluster. Availability and implementation: Source code and binaries are freely available at http://meringlab.org/software/hpc-clust/; the pipeline is implemented in C++ and uses the Message Passing Interface (MPI) standard for distributed computing. CONTACT: [email protected] SUPPLEMENTARY INFORMATION:  Supplementary data are available at Bioinformatics online

    Differential regulation of Toll-like receptor mRNAs in experimental murine central nervous system infections

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    Toll-like receptors (TLR) play a key role in the recognition of microbial components. We investigated the differential regulation of TLR mRNA expression in bacterial and viral mouse models of central nervous system infection. Streptococcus pneumoniae meningitis led to an enhanced expression of TLR2, TLR4 and TLR9 mRNA. In Escherichia coli meningitis, TLR2, TLR4 and TLR7 mRNA expression was increased and Herpes simplex encephalitis caused a rise of TLR4 mRNA. In organotypic hippocampal cultures treatment with S. pneumoniae R6 led to increased expression of TLR2 and TLR3 mRNA. Our data provide evidence that regulation of TLR mRNA is not fully specific for the molecular patterns of the infectious pathogen. The TLR mRNA regulation observed probably represents a combination of specific response to the causative pathogen and non-specific activation of the innate immune system. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved

    Long-term working-time accounts and life-course policies: Preliminary results of a representative company survey

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    The paper introduces the basic concept and functioning of long-term workingtime accounts and discusses major trends, risks and opportunities with regard to life-course oriented working-time adjustments. It gives a detailed overview of the distribution and use of long-term working-time accounts in Germany. This overview is based on initial multivariate analyses of a representative company survey that was carried out in 2005. The main questions concern the individual options and opportunities offered by long-term working-time accounts and the characteristics of their distribution. We examine effects of firm size, sector, demand fluctuations, economic performance, personnel policy, industrial relations, and workforce composition. There is empirical evidence that the distribution and use of long-term working-time accounts is strongly influenced by company size and the presence of a works- or staff council in the company. Larger companies with works or staff councils have more frequently long-term working-time accounts and use them predominantly for early or progressive retirement options, even more when the share of male employees in the company is high. -- Der Artikel stellt das relativ neue Arbeitszeitinstrument betrieblicher Langzeitkonten vor und untersucht deren Entwicklung und Potenziale hinsichtlich einer lebensphasenorientierten Arbeitszeitgestaltung. Anhand multivariater Auswertungen wird die Verbreitung und Nutzung von Langzeitkonten in der Bundesrepublik Deutschland analysiert. Basis ist eine repräsentative Unternehmensbefragung, die im Herbst 2005 durchgeführt wurde. Leitend ist die Frage nach Unterschieden der Verbreitung von Langzeitkonten und den damit verbundenen Arbeitszeitoptionen für die Beschäftigten. Dabei werden grundlegende Betriebsmerkmale berücksichtigt, wie Größe, Marktsituation, Personalpolitik, industrielle Beziehungen und Beschäftigungsstruktur. Es zeigen sich deutliche Unterschiede nach der Betriebsgröße und dem Vorhandensein einer betrieblichen Interessenvertretung. Größere Unternehmen mit Betriebs- oder Personalrat verfügen häufiger über Langzeitkonten und nutzen diese vorrangig für den vorzeitigen oder gleitenden Ruhestand.

    STRING and STITCH: known and predicted interactions between proteins and chemicals

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    Information on protein-protein and protein-chemical interactions is essential for understanding cellular functions. The STRING and STITCH web resources integrate interaction evidence derived from pathways, automatic literature mining, primary experimental data, and genomic context. The resulting interaction networks cover 1.5 million proteins from 373 organisms and 68,000 chemicals
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