Computational Cancer Biology: An Evolutionary Perspective

ISSN:1553-734XISSN:1553-735

Coalition theories: empirical evidence for dutch municipalities

The paper analyzes coalition formation in Dutch municipalities. After discussing the main features of the institutional setting, several theories are discussed, which are classified as size oriented, policy oriented and actor oriented models. A test statistic is proposed to determine the predictive power of these models. The empirical analysis shows that strategic positions as well as some of the distinguished preferences are important in the setting of Dutch municipalities. Especially, the dominant minimum number principle yields highly significant results for coalition formations in the period 1978–1986

On cycles in the transcription network of Saccharomyces cerevisiae

<p>Abstract</p> <p>Background</p> <p>We investigate the cycles in the transcription network of <it>Saccharomyces cerevisiae</it>. Unlike a similar network of <it>Escherichia coli</it>, it contains many cycles. We characterize properties of these cycles and their place in the regulatory mechanism of the cell.</p> <p>Results</p> <p>Almost all cycles in the transcription network of <it>Saccharomyces cerevisiae </it>are contained in a single <it>strongly connected component</it>, which we call LSCC (L for "largest"), except for a single cycle of two transcription factors. The fact that LSCC includes almost all cycles is well explained by the properties of a random graph with the same in- and out-degrees of the nodes.</p> <p>Among different physiological conditions, cell cycle has the most significant relationship with LSCC, as the set of 64 transcription interactions that are active in all phases of the cell cycle has overlap of 27 with the interactions of LSCC (of which there are 49).</p> <p>Conversely, if we remove the interactions that are active in all phases of the cell cycle (25% of interactions to transcription factors), the LSCC would have only three nodes and 5 edges, many fewer than expected. This subgraph of the transcription network consists mostly of interactions that are active only in the stress response subnetwork.</p> <p>We also characterize the role of LSCC in the topology of the network. We show that LSCC can be used to define a natural hierarchy in the network and that in every physiological subnetwork LSCC plays a pivotal role.</p> <p>Conclusion</p> <p>Apart from those well-defined conditions, the transcription network of <it>Saccharomyces cerevisiae </it>is devoid of cycles. It was observed that two conditions that were studied and that have no cycles of their own are <it>exogenous</it>: diauxic shift and DNA repair, while cell cycle and sporulation are <it>endogenous</it>. We claim that in a certain sense (slow recovery) stress response is <it>endogenous </it>as well.</p

An events based algorithm for distributing concurrent tasks on multi-core architectures

In this paper, a programming model is presented which enables scalable parallel performance on multi-core shared memory architectures. The model has been developed for application to a wide range of numerical simulation problems. Such problems involve time stepping or iteration algorithms where synchronization of multiple threads of execution is required. It is shown that traditional approaches to parallelism including message passing and scatter-gather can be improved upon in terms of speed-up and memory management. Using spatial decomposition to create orthogonal computational tasks, a new task management algorithm called H-Dispatch is developed. This algorithm makes efficient use of memory resources by limiting the need for garbage collection and takes optimal advantage of multiple cores by employing a “hungry” pull strategy. The technique is demonstrated on a simple finite difference solver and results are compared to traditional MPI and scatter-gather approaches. The H-Dispatch approach achieves near linear speed-up with results for efficiency of 85% on a 24-core machine. It is noted that the H-Dispatch algorithm is quite general and can be applied to a wide class of computational tasks on heterogeneous architectures involving multi-core and GPGPU hardware.Schlumberger-Doll Research CenterSaudi Aramc

Genome-wide association analysis of insomnia complaints identifies risk genes and genetic overlap with psychiatric and metabolic traits.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesPersistent insomnia is among the most frequent complaints in general practice. To identify genetic factors for insomnia complaints, we performed a genome-wide association study (GWAS) and a genome-wide gene-based association study (GWGAS) in 113,006 individuals. We identify three loci and seven genes associated with insomnia complaints, with the associations for one locus and five genes supported by joint analysis with an independent sample (n = 7,565). Our top association (MEIS1, P < 5 × 10-8) has previously been implicated in restless legs syndrome (RLS). Additional analyses favor the hypothesis that MEIS1 exhibits pleiotropy for insomnia and RLS and show that the observed association with insomnia complaints cannot be explained only by the presence of an RLS subgroup within the cases. Sex-specific analyses suggest that there are different genetic architectures between the sexes in addition to shared genetic factors. We show substantial positive genetic correlation of insomnia complaints with internalizing personality traits and metabolic traits and negative correlation with subjective well-being and educational attainment. These findings provide new insight into the genetic architecture of insomnia.Netherlands Organization for Scientific Research NWO Brain & Cognition 433-09-228 European Research Council ERC-ADG-2014-671084 INSOMNIA Netherlands Scientific Organization (NWO) VU University (Amsterdam, the Netherlands) Dutch Brain Foundation Helmholtz Zentrum Munchen - German Federal Ministry of Education and Research state of Bavaria German Migraine & Headache Society (DMKG) Almirall AstraZeneca Berlin Chemie Boehringer Boots Health Care GlaxoSmithKline Janssen Cilag McNeil Pharma MSD Sharp Dohme Pfizer Institute of Epidemiology and Social Medicine at the University of Munster German Ministry of Education and Research (BMBF) German Restless Legs Patient Organisation (RLS Deutsche Restless Legs Vereinigung) Swiss RLS Patient Association (Schweizerische Restless Legs Selbsthilfegruppe

Hemotin, a regulator of phagocytosis encoded by a small ORF and xonserved across metazoans

Translation of hundreds of small ORFs (smORFs) of less than 100 amino acids has recently been revealed in vertebrates and Drosophila. Some of these peptides have essential and conserved cellular functions. In Drosophila, we have predicted a particular smORF class encoding ~80 aa hydrophobic peptides, which may function in membranes and cell organelles. Here, we characterise hemotin, a gene encoding an 88aa transmembrane smORF peptide localised to early endosomes in Drosophila macrophages. hemotin regulates endosomal maturation during phagocytosis by repressing the cooperation of 14-3-3ζ with specific phosphatidylinositol (PI) enzymes. hemotin mutants accumulate undigested phagocytic material inside enlarged endo-lysosomes and as a result, hemotin mutants have reduced ability to fight bacteria, and hence, have severely reduced life span and resistance to infections. We identify Stannin, a peptide involved in organometallic toxicity, as the Hemotin functional homologue in vertebrates, showing that this novel regulator of phagocytic processing is widely conserved, emphasizing the significance of smORF peptides in cell biology and disease