Pathway-Based Genomics Prediction using Generalized Elastic Net.

We present a novel regularization scheme called The Generalized Elastic Net (GELnet) that incorporates gene pathway information into feature selection. The proposed formulation is applicable to a wide variety of problems in which the interpretation of predictive features using known molecular interactions is desired. The method naturally steers solutions toward sets of mechanistically interlinked genes. Using experiments on synthetic data, we demonstrate that pathway-guided results maintain, and often improve, the accuracy of predictors even in cases where the full gene network is unknown. We apply the method to predict the drug response of breast cancer cell lines. GELnet is able to reveal genetic determinants of sensitivity and resistance for several compounds. In particular, for an EGFR/HER2 inhibitor, it finds a possible trans-differentiation resistance mechanism missed by the corresponding pathway agnostic approach

Syncope and the drive towards minimization in Colloquial Bamana

Data from two varieties of Bamana, a Mande language spoken in West Africa, illustrate that permissible syllable shapes vary between the two types. A comparison of Classic Bamana spoken in Segou, Mali and that spoken by a younger cohort of individuals in the Malian capital, Bamako, reveals that the latter variety is synchronically developing complex CCV and CVC syllable shapes, whereas the classical variety permits only maximal CV syllables. We posit that the development of these syllable shapes represents an overall drive towards word minimization in this variety of the language. This study formalizes minimization in Colloquial Bamana in an optimality theoretic framework and illustrates the support that these developing processes in Bamana provide for the Split Margin Approach to the syllable, developed in Baertsch (2002). Preferential deletion patterns, the role of phonotactics in driving these patterns, and other processes interacting with and/or preventing syncope from occurring are also explored.National Institutes of Health DC00433, RR7031K, DC00076, DC001694 (PI: Gierut

Effects of various meteorological conditions and spatial emissionresolutions on the ozone concentration and ROG/NO_x limitationin the Milan area (I)

The three-dimensional photochemical model UAM-V is used to investigate the effects of various meteorological conditions and of the coarseness of emission inventories on the ozone concentration and ROG/NO_x limitation of the ozone production in the Po Basin in the northern part of Italy. As a base case, the high ozone episode with up to 200ppb on 13 May 1998 was modelled and previously thoroughly evaluated with measurements gained during a large field experiment. Systematic variations in meteorology are applied to mixing height, air temperature, specific humidity and wind speed. Three coarser emission inventories are obtained by resampling from 3x3km² up to 54x54km² emission grids. The model results show that changes in meteorological input files strongly influence ozone in this area. For instance, temperature changes peak ozone by 10.1ppb/&degC and the ozone concentrations in Milan by 2.8ppb/&degC. The net ozone formation in northern Italy is more strongly temperature than humidity dependent, while the humidity is very important for the ROG/NO_x limitation of the ozone production. For all meteorological changes (e.g. doubling the mixing height), the modelled peak ozone remains ROG limited. A strong change towards NO_x sensitivity in the ROG limited areas is only found if much coarser emission inventories were applied. Increasing ROG limited areas with increasing wind speed are found, because the ROG limited ozone chemistry induced by point sources is spread over a larger area. Simulations without point sources tend to increase the NO_x limited areas

Retrocopy contributions to the evolution of the human genome

<p>Abstract</p> <p>Background</p> <p>Evolution via point mutations is a relatively slow process and is unlikely to completely explain the differences between primates and other mammals. By contrast, 45% of the human genome is composed of retroposed elements, many of which were inserted in the primate lineage. A subset of retroposed mRNAs (retrocopies) shows strong evidence of expression in primates, often yielding functional retrogenes.</p> <p>Results</p> <p>To identify and analyze the relatively recently evolved retrogenes, we carried out BLASTZ alignments of all human mRNAs against the human genome and scored a set of features indicative of retroposition. Of over 12,000 putative retrocopy-derived genes that arose mainly in the primate lineage, 726 with strong evidence of transcript expression were examined in detail. These mRNA retroposition events fall into three categories: I) 34 retrocopies and antisense retrocopies that added potential protein coding space and UTRs to existing genes; II) 682 complete retrocopy duplications inserted into new loci; and III) an unexpected set of 13 retrocopies that contributed out-of-frame, or antisense sequences in combination with other types of transposed elements (SINEs, LINEs, LTRs), even unannotated sequence to form potentially novel genes with no homologs outside primates. In addition to their presence in human, several of the gene candidates also had potentially viable ORFs in chimpanzee, orangutan, and rhesus macaque, underscoring their potential of function.</p> <p>Conclusion</p> <p>mRNA-derived retrocopies provide raw material for the evolution of genes in a wide variety of ways, duplicating and amending the protein coding region of existing genes as well as generating the potential for new protein coding space, or non-protein coding RNAs, by unexpected contributions out of frame, in reverse orientation, or from previously non-protein coding sequence.</p

The UCSC Archaeal Genome Browser

As more archaeal genomes are sequenced, effective research and analysis tools are needed to integrate the diverse information available for any given locus. The feature-rich UCSC Genome Browser, created originally to annotate the human genome, can be applied to any sequenced organism. We have created a UCSC Archaeal Genome Browser, available at , currently with 26 archaeal genomes. It displays G/C content, gene and operon annotation from multiple sources, sequence motifs (promoters and Shine-Dalgarno), microarray data, multi-genome alignments and protein conservation across phylogenetic and habitat categories. We encourage submission of new experimental and bioinformatic analysis from contributors. The purpose of this tool is to aid biological discovery and facilitate greater collaboration within the archaeal research community

Finite-element modeling and optimization of 3D-printed auxetic reentrant structures with stiffness gradient under low-velocity impact

Additive manufacturing technologies such as fused filament fabrication (FFF) allow the production of metastructures with global properties that can be tailored to their specific application. This study simulated and optimized an auxetic re-entrant structure with a stiffness gradient for enhanced energy absorption with low acceleration peaks under different low-velocity impact conditions. The finite-element method (FEM) was used, and appropriate constitutive models were fitted to static and dynamic tensile and compressive data of acrylonitrile butadiene styrene (ABS) tested under various strain rates. A Johnson–Cook plasticity model demonstrated the best compromise between accuracy and computational efficiency. A simulation strategy using explicit FEM was developed to simulate additively manufactured auxetic metastructures under impact conditions. There was good agreement between the model prediction and the experimentally observed structural response. A parametric optimization was implemented to enhance the energy absorption capability with low acceleration peaks of a graded auxetic re-entrant structure for different impact velocities

Nanoparticulate matter exposure results in white matter damage and an inflammatory microglial response in an experimental murine model

Exposure to ambient air pollution has been associated with white matter damage and neurocognitive decline. However, the mechanisms of this injury are not well understood and remain largely uncharacterized in experimental models. Prior studies have shown that exposure to particulate matter (PM), a sub-fraction of air pollution, results in neuroinflammation, specifically the upregulation of inflammatory microglia. This study examines white matter and axonal injury, and characterizes microglial reactivity in the corpus callosum of mice exposed to 10 weeks (150 hours) of PM. Nanoscale particulate matter (nPM, aerodynamic diameter ≤200 nm) consisting primarily of traffic-related emissions was collected from an urban area in Los Angeles. Male C57BL/6J mice were exposed to either re-aerosolized nPM or filtered air for 5 hours/day, 3 days/week, for 10 weeks (150 hours; n = 18/group). Microglia were characterized by immunohistochemical double staining of ionized calcium-binding protein-1 (Iba-1) with inducible nitric oxide synthase (iNOS) to identify pro-inflammatory cells, and Iba-1 with arginase-1 (Arg) to identify anti-inflammatory/ homeostatic cells. Myelin injury was assessed by degraded myelin basic protein (dMBP). Oligodendrocyte cell counts were evaluated by oligodendrocyte transcription factor 2 (Olig2). Axonal injury was assessed by axonal neurofilament marker SMI-312. iNOS-expressing microglia were significantly increased in the corpus callosum of mice exposed to nPM when compared to those exposed to filtered air (2.2 fold increase; p\u3c0.05). This was accompanied by an increase in dMBP (1.4 fold increase; p\u3c0.05) immunofluorescent density, a decrease in oligodendrocyte cell counts (1.16 fold decrease; p\u3c0.05), and a decrease in neurofilament SMI-312 (1.13 fold decrease; p\u3c0.05) immunofluorescent density. Exposure to nPM results in increased inflammatory microglia, white matter injury, and axonal degradation in the corpus callosum of adult male mice. iNOS-expressing microglia release cytokines and reactive oxygen/ nitrogen species which may further contribute to the white matter damage observed in this model

Sustainability? Population Affluence Species Technology

Presentation on algae and sustainability of the earth. Discusses the Offshore Membrane Enclosures for Growing Algae (OMEGA)