Topology and shape optimization of induced-charge electro-osmotic micropumps

For a dielectric solid surrounded by an electrolyte and positioned inside an externally biased parallel-plate capacitor, we study numerically how the resulting induced-charge electro-osmotic (ICEO) flow depends on the topology and shape of the dielectric solid. In particular, we extend existing conventional electrokinetic models with an artificial design field to describe the transition from the liquid electrolyte to the solid dielectric. Using this design field, we have succeeded in applying the method of topology optimization to find system geometries with non-trivial topologies that maximize the net induced electro-osmotic flow rate through the electrolytic capacitor in the direction parallel to the capacitor plates. Once found, the performance of the topology optimized geometries has been validated by transferring them to conventional electrokinetic models not relying on the artificial design field. Our results show the importance of the topology and shape of the dielectric solid in ICEO systems and point to new designs of ICEO micropumps with significantly improved performance.Comment: 18 pages, latex IOP-style, 7 eps figure

Enrichment of Genetic Variants for Rheumatoid Arthritis within T-Cell and NK-Cell Enhancer Regions

To identify disease-causative variants, we intersected the published results of a metaanalysis of genome-wide association studies (GWAS) for rheumatoid arthritis (RA) with the set of enhancer regions for 71 primary cell types that was provided by the FANTOM consortium. We first retrieved all single nucleotide polymorphisms (SNPs) that are associated (P \u3c 5 x 10(8)) with RA in the GWAS meta-analysis and that are located in any of these enhancer regions. After excluding the major histocompatibility complex (MHC) region, we identified 50 such RA-associated SNPs that are located in enhancer regions. Enhancer sets from different cell types were then compared with each other for their number of RA-associated SNPs by permutation analysis. This analysis showed that RA-associated SNPs are preferentially located in enhancers from several immunological cell types. In particular, we see a strong relative enrichment in enhancer regions that are active in T cells (P \u3c 0.001) and NK cells (P \u3c 0.001). Several loci display multiple RA-associated SNPs in tight linkage disequilibrium that are located within the same or neighboring enhancers. These haplotypes may have a greater likelihood to influence enhancer activity than any SNP on its own. Taken together, these results support the hypothesis that RA-causative variants often act through altering the activity of immune cell enhancers. The enrichment in T-cell and NK-cell enhancer regions indicates that expression changes in these cell types are particularly relevant for the pathogenesis of RA. The specific SNPs that account for this enrichment can be used as a basis for focused genotype-phenotype studies of these cell types

OpenMI: the essential concepts and their implications for legacy software

International audienceInformation & Communication Technology (ICT) tools such as computational models are very helpful in designing river basin management plans (rbmp-s). However, in the scientific world there is consensus that a single integrated modelling system to support e.g. the implementation of the Water Framework Directive cannot be developed and that integrated systems need to be very much tailored to the local situation. As a consequence there is an urgent need to increase the flexibility of modelling systems, such that dedicated model systems can be developed from available building blocks. The HarmonIT project aims at precisely that. Its objective is to develop and implement a standard interface for modelling components and other relevant tools: The Open Modelling Interface (OpenMI) standard. The OpenMI standard has been completed and documented. It relies entirely on the "pull" principle, where data are pulled by one model from the previous model in the chain. This paper gives an overview of the OpenMI standard, explains the foremost concepts and the rational behind it

A Role for Noncoding Variation in Schizophrenia

A large portion of common variant loci associated with genetic risk for schizophrenia reside within noncoding sequence of unknown function. Here, we demonstrate promoter and enhancer enrichment in schizophrenia variants associated with expression quantitative trait loci (eQTL). The enrichment is greater when functional annotations derived from the human brain are used relative to peripheral tissues. Regulatory trait concordance analysis ranked genes within schizophrenia genome-wide significant loci for a potential functional role, based on colocalization of a risk SNP, eQTL, and regulatory element sequence. We identified potential physical interactions of noncontiguous proximal and distal regulatory elements. This was verified in prefrontal cortex and -induced pluripotent stem cell-derived neurons for the L-type calcium channel (CACNA1C) risk locus. Our findings point to a functional link between schizophrenia-associated noncoding SNPs and 3D genome architecture associated with chromosomal loopings and transcriptional regulation in the brain