A machine learning strategy to identify candidate binding sites in human protein-coding sequence

BACKGROUND: The splicing of RNA transcripts is thought to be partly promoted and regulated by sequences embedded within exons. Known sequences include binding sites for SR proteins, which are thought to mediate interactions between splicing factors bound to the 5' and 3' splice sites. It would be useful to identify further candidate sequences, however identifying them computationally is hard since exon sequences are also constrained by their functional role in coding for proteins. RESULTS: This strategy identified a collection of motifs including several previously reported splice enhancer elements. Although only trained on coding exons, the model discriminates both coding and non-coding exons from intragenic sequence. CONCLUSION: We have trained a computational model able to detect signals in coding exons which seem to be orthogonal to the sequences' primary function of coding for proteins. We believe that many of the motifs detected here represent binding sites for both previously unrecognized proteins which influence RNA splicing as well as other regulatory elements

Managing Activities at Wineries: Building and Sustaining a Place-Based Brand

The Willamette Valley Winery Association, Oregon Winery Association, Oregon Department of Land Conservation and Development, and Oregon Department of Agriculture asked the authors to develop information needed to help inform discussions regarding the replacement for the soon-to-sunset HB 3280. HB 3280, signed by the Governor in August of 2011, provided a means for defining and regulating wine-related and non-wine-related events occurring or proposed to occur at wineries and vineyards in Oregon, often in exclusive farm use zones. Our charge was to investigate the following policy issue: How have wine regions permitted and managed a range of uses and activities at wineries, some of which are indirectly connected to the making or selling of wine? How can wine region land use regulations contribute to sustaining the brand for a region? How can farmland winery codes best maintain compatibility with other crops and farming activities? This report is presented in three parts. We begin with the literature review, and the lessons learned from that research. We then present the four cases and the lessons learned from them. This report concludes with a synthesis of the findings from the literature review and the case studies, along with our recommendations for how this information might be applied to the development of a replacement for HB 3280 in the next legislative session

Synthetic Food Colors and Neurobehavioral Hazards: The View from Environmental Health Research

Background: The proposition that synthetic food colors can induce adverse behavioral effects in children was first enunciated in 1975 by Feingold [Why Your Child Is Hyperactive. New York:Random House (1975)], who asserted that elevated sensitivity to food additives underlies the signs of hyperactivity observed in some children. Although the evidence suggested that some unknown proportion of children did respond to synthetic food colors, the U.S. Food and Drug Administration (FDA) interpreted the evidence as inconclusive. A study published in 2007 [McCann et al. Food additives and hyperactive behaviour in 3-year-old and 8/9-year-old children in the community: a randomised, double-blinded, placebo-controlled trial. Lancet 370:1560–1567 (2007)] drew renewed attention to the hypothesis because of the study’s size and scope. It led the FDA to review the evidence, hold a public hearing, and seek the advice of its Food Advisory Committee. In preparation for the hearing, the FDA reviewed the available evidence and concluded that it did not warrant further agency action

Microstructural Characterization of Graphite Spheroids in Ductile Iron

The present work brings new insights by transmission electron microscopy allowing disregarding or supporting some of the models proposed for spheroidal growth of graphite in cast irons. Nodules consist of sectors made of graphite plates elongated along a hai direction and stack on each other with their c axis aligned with the radial direction. These plates are the elementary units for spheroidal growth and a calculation supports the idea that new units continuously nucleate at the ledge between sectors

dynamic Flux Balance Analysis of the Metabolism of Microalgae under a Diurnal Light Cycle

Microalgae have received much attention in the context of renewable fuel production, due to their ability to produce in high quantities carbon storage molecules such as lipids and carbohydrates. Despite significant research effort over the last decade, the production yields remain low and need to be optimized. For that, a thorough understanding of carbon storage metabolism is necessary. This paper develops a constrained metabolic model based on the dFBA framework to represent the dynamics of carbon storage in microalgae under a diurnal light cycle. The main assumption here is that microalgae adapt their metabolism in order to optimize their production of functional biomass (proteins, membrane lipids, DNA, RNA) over a diurnal cycle. A generic metabolic network comprised of 160 reactions representing the main carbon and nitrogen pathways of microalgae is used to characterize the metabolism. The optimization problem is simplified by exploiting the right kernel of the stoichiometric matrix, and transformed into a linear program by discretizing the differential equations using a classical collocation technique. Several constraints are investigated. The results suggest that the experimentally observed strategy of accumulation of carbon storage molecules during the day, followed by their depletion during the night may indeed be the optimal one. However, a constraint on the maximal synthesis rate of functional biomass must be added for consistency with the biological observations

Confounders in the assessment of the renal effects associated with low-level urinary cadmium: an analysis in industrial workers

<p>Abstract</p> <p>Background</p> <p>Associations of proteinuria with low-level urinary cadmium (Cd) are currently interpreted as the sign of renal dysfunction induced by Cd. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins.</p> <p>Methods</p> <p>We examined 184 healthy male workers (mean age, 39.5 years) from a zinc smelter (n = 132) or a blanket factory (n = 52). We measured the concentrations of Cd in blood (B-Cd) and the urinary excretion of Cd (U-Cd), retinol-binding protein (RBP), protein HC and albumin. Associations between biomarkers of metal exposure and urinary proteins were assessed by simple and multiple regression analyses.</p> <p>Results</p> <p>The medians (interquartile range) of B-Cd (μg/l) and U-Cd (μg/g creatinine) were 0.80 (0.45-1.16) and 0.70 (0.40-1.3) in smelter workers and 0.66 (0.47-0.87) and 0.55 (0.40-0.90) in blanket factory workers, respectively. Occupation had no influence on these values, which varied mainly with smoking habits. In univariate analysis, concentrations of RBP and protein HC in urine were significantly correlated with both U-Cd and B-Cd but these associations were substantially weakened by the adjustment for current smoking and the residual influence of diuresis after correction for urinary creatinine. Albumin in urine did not correlate with B-Cd but was consistently associated with U-Cd through a relationship, which was unaffected by smoking or diuresis. Further analyses showed that RBP and albumin in urine mutually distort their associations with U-Cd and that the relationship between RBP and Cd in urine was almost the replicate of that linking RBP to albumin</p> <p>Conclusions</p> <p>Associations between proteinuria and low-level urinary Cd should be interpreted with caution as they appear to be largely driven by diuresis, current smoking and probably also the co-excretion of Cd with plasma proteins.</p

Wall Crossing and Instantons in Compactified Gauge Theory

We calculate the leading weak-coupling instanton contribution to the moduli-space metric of N=2 supersymmetric Yang-Mills theory with gauge group SU(2) compactified on R^3 x S^1. The results are in precise agreement with the semiclassical expansion of the exact metric recently conjectured by Gaiotto, Moore and Neitzke based on considerations related to wall-crossing in the corresponding four-dimensional theory.Comment: 24 pages, no figure