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Schmidt B.J.,University of Virginia | Schmidt B.J.,Entelos | Lin-Schmidt X.,University of Virginia | Chamberlin A.,University of Virginia | And 3 more authors.
Biotechnology Journal | Year: 2010

Algal fuel sources promise unsurpassed yields in a carbon neutral manner that minimizes resource competition between agriculture and fuel crops. Many challenges must be addressed before algal biofuels can be accepted as a component of the fossil fuel replacement strategy. One significant challenge is that the cost of algal fuel production must become competitive with existing fuel alternatives. Algal biofuel production presents the opportunity to fine-tune microbial metabolic machinery for an optimal blend of biomass constituents and desired fuel molecules. Genome-scale model-driven algal metabolic design promises to facilitate both goals by directing the utilization of metabolites in the complex, interconnected metabolic networks to optimize production of the compounds of interest. Network analysis can direct microbial development efforts towards successful strategies and enable quantitative fine-tuning of the network for optimal product yields while maintaining the robustness of the production microbe. Metabolic modeling yields insights into microbial function, guides experiments by generating testable hypotheses, and enables the refinement of knowledge on the specific organism. While the application of such analytical approaches to algal systems is limited to date, metabolic network analysis can improve understanding of algal metabolic systems and play an important role in expediting the adoption of new biofuel technologies. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA. Source

Murray C.,Trinity College Dublin | Huerta-Sanchez E.,University of California at Berkeley | Casey F.,Entelos | Bradley D.G.,Trinity College Dublin
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2010

The phylogeography of cattle genetic variants has been extensively described and has informed the history of domestication. However, there remains a dearth of demographic models inferred from such data. Here, we describe sequence diversity at 37 000 bp sampled from 17 genes in cattle from Africa, Europe and India. Clearly distinct population histories are suggested between Bos indicus and Bos taurus, with the former displaying higher diversity statistics. We compare the unfolded site frequency spectra in each to those simulated using a diffusion approximation method and build a best-fitting model of past demography. This implies an earlier, possibly glaciation-induced population bottleneck in B. taurus ancestry with a later, possibly domestication-associated demographic constriction in B. indicus. Strikingly, the modelled indicine history also requires a majority secondary admixture from the South Asian aurochs, indicating a complex, more diffuse domestication process. This perhaps involved multiple domestications and/or introgression from wild oxen to domestic herds; the latter is plausible from archaeological evidence of contemporaneous wild and domestic remains across different regions of South Asia. © 2010 The Royal Society. Source

Ragkousi K.,University of Arizona | Beh J.,University of California at Berkeley | Beh J.,Entelos | Sweeney S.,University of Arizona | And 3 more authors.
Developmental Biology | Year: 2011

GATA family transcription factors are core components of the vertebrate heart gene network. GATA factors also contribute to heart formation indirectly through regulation of endoderm morphogenesis. However, the precise impact of GATA factors on vertebrate cardiogenesis is masked by functional redundancy within multiple lineages. Early heart specification in the invertebrate chordate Ciona intestinalis is similar to that of vertebrates but only one GATA factor, Ci-GATAa, is expressed in the heart progenitor cells and adjacent endoderm. Here we delineate precise, tissue specific contributions of GATAa to heart formation. Targeted repression of GATAa activity in the heart progenitors perturbs their transcriptional identity. Targeted repression of endodermal GATAa function disrupts endoderm morphogenesis. Subsequently, the bilateral heart progenitors fail to fuse at the ventral midline. The resulting phenotype is strikingly similar to cardia bifida, as observed in vertebrate embryos when endoderm morphogenesis is disturbed. These findings indicate that GATAa recapitulates cell-autonomous and non-cell-autonomous roles performed by multiple, redundant GATA factors in vertebrate cardiogenesis. © 2011 . Source

Entelos | Date: 2010-12-14

Methods and apparatus to identify a potential toxicity of a therapy in a biological system are described. In one embodiment, a method uses a computer model that represents a set of biological processes of the biological system. The method includes executing the computer model to identify a first set of biological processes contributing to the occurrence of a toxic state of the biological system. The method also includes identifying a set of biological assays based on the first set of biological processes and testing the therapy in the set of biological assays to identify a second set of biological processes modified by the therapy. The method further includes identifying the potential toxicity of the therapy based on the second set of biological processes.

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