Slope dependence of self-similar structure and entrainment in gravity currents

Results from seven direct and large-eddy simulations of gravity currents on slopes ranging from 0.14° to 2.86° that span from the subcritical to the supercritical regime are studied. By considering a long domain, attention is focused on the near-self-similar state approached by these currents far downstream. In the self-similar limit, the various shape factors, local Richardson number, entrainment coefficient, velocity scale and basal drag coefficient reach a constant value, while the current height, volume and momentum fluxes continue to increase linearly. Their dependence on slope is presented.Fil: Salinas, Jorge S.. University of Florida; Estados UnidosFil: Zúñiga, Santiago Luciano. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Cantero, Mariano Ignacio. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Shringarpure, M.. No especifíca;Fil: Fedele, J.. No especifíca;Fil: Hoyal, D.. No especifíca;Fil: Balachandar, S.. University of Florida; Estados Unido

On the definition, evolution, and properties of the outer edge of gravity currents: A direct-numerical and large-eddy simulation study

Gravity currents are flows driven by the action of gravity over fluids with different densities. Here, we focus on gravity currents where heavier fluid travels along the bottom of a sloping bed, underneath a large body of stagnant lighter ambient fluid. The thickness of the current increases due to entrainment of ambient fluid into the current. Direct numerical and large eddy simulations of gravity currents and a wall-jet transporting a passive scalar field are performed. We focus on the rate of penetration of mean momentum and mean concentration of the agent responsible for the density difference (temperature, salinity, or sediment volume fraction) into the ambient fluid. The rates of penetration of turbulence-related quantities (i.e., turbulent kinetic energy, Reynolds flux, and stress) into the ambient are analyzed. A robust methodology for defining the upper edge of these quantities and thereby defining the current thickness using these different mean and turbulent quantities is presented. A comparison between downstream evolution of the gravity current with the corresponding behaviors of canonical wall-bounded turbulent flows is presented. The present understanding of turbulent/non-turbulent interface (TNTI) is extended to include subcritical flows where, due to the strong effect of stratification, the TNTI is buried well within the upper edge of the current and confined right above the inner near-bed layer. The present work sheds light on the striking difference between the different definitions of thickness (momentum, concentration, turbulence, etc.) in subcritical gravity currents, where stratification suppresses turbulence in the upper region of the current.Fil: Salinas, Jorge S.. University of Florida; Estados UnidosFil: Balachandar, S.. University of Florida; Estados UnidosFil: Zúñiga, Santiago Luciano. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Shringarpure, M.. No especifíca;Fil: Fedele, J.. No especifíca;Fil: Hoyal, D.. No especifíca;Fil: Cantero, Mariano Ignacio. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Anatomy of subcritical submarine flows with a lutocline and an intermediate destruction layer

Turbidity currents are sediment-laden flows that travel over a sloping bed under a stagnant ambient fluid, driven by the density difference between the current and the ambient. Turbidity currents transport large amounts of carbon, nutrients and fresh water through oceans and play an important role in global geochemical cycling and seafloor ecosystems. Supercritical currents are observed in steeper slopes. Subcritical currents are observed in milder slopes, where the near-bed and interface layers are prevented from interacting across the velocity maximum. Past works show the existence of such a barrier to vertical momentum transfer is essential for the body of the subcritical current to extend over hundreds of kilometers in length without much increase in height. Here we observe the body of subcritical currents to have a three layer structure, where the turbulent near-bed layer and the non-turbulent interface layer are separated by an intermediate layer of negative turbulence production. We explain the mechanism by which this layer prevents the near-bed turbulent structures from penetrating into the interface layer by transferring energy back from turbulence to the mean flow.Fil: Salinas, Jorge Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. University of Florida; Estados UnidosFil: Balachandar, S.. University of Florida; Estados UnidosFil: Shringarpure, M.. No especifíca;Fil: Fedele, J.. No especifíca;Fil: Hoyal, D.. No especifíca;Fil: Zúñiga, Santiago Luciano. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; ArgentinaFil: Cantero, Mariano Ignacio. Comisión Nacional de Energía Atómica. Gerencia del Área de Energía Nuclear. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro | Universidad Nacional de Cuyo. Instituto Balseiro. Archivo Histórico del Centro Atómico Bariloche e Instituto Balseiro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte; Argentin

Continuing mortality of vultures in India associated with illegal veterinary use of diclofenac and a potential threat from nimesulide

AbstractThe collapse of South Asia's Gyps vulture populations is attributable to the veterinary use of the non-steroidal anti-inflammatory drug (NSAID) diclofenac. Vultures died after feeding on carcasses of recently-medicated animals. The governments of India, Nepal and Pakistan banned the veterinary use of diclofenac in 2006. We analysed results of 62 necropsies and 48 NSAID assays of liver and/or kidney for vultures of five species found dead in India between 2000 and 2012. Visceral gout and diclofenac were detected in vultures from nine states and three species: Gyps bengalensis, Gyps indicus and Gyps himalayensis. Visceral gout was found in every vulture carcass in which a measurable level of diclofenac was detected. Meloxicam, an NSAID of low toxicity to vultures, was found in two vultures and nimesulide in five vultures. Nimesulide at elevated tissue concentrations was associated with visceral gout in four of these cases, always without diclofenac, suggesting that nimesulide may have similar toxic effects to those of diclofenac. Residues of meloxicam on its own were never associated with visceral gout. The proportion of Gyps vultures found dead in the wild in India with measurable levels of diclofenac in their tissues showed a modest and non-significant decline since the ban on the veterinary use of diclofenac. The prevalence of visceral gout declined less, probably because some cases of visceral gout from 2008 onwards were associated with nimesulide rather than diclofenac. Veterinary use of nimesulide is a potential threat to the recovery of vulture populations.Financial support and assistance for the project from the Director, Indian Veterinary Research Institute (IVRI), the UK Government’s Darwin Initiative and the Royal Society for the Protection of Birds is gratefully acknowledged.This is the accepted manuscript. The final version is available from Cambridge University Press via http://dx.doi.org/10.1017/S003060531500037

Sharing health-related data:A privacy test?

Greater sharing of potentially sensitive data raises important ethical, legal and social issues (ELSI), which risk hindering and even preventing useful data sharing if not properly addressed. One such important issue is respecting the privacy-related interests of individuals whose data are used in genomic research and clinical care. As part of the Global Alliance for Genomics and Health (GA4GH), we examined the ELSI status of health-related data that are typically considered ‘sensitive’ in international policy and data protection laws. We propose that ‘tiered protection’ of such data could be implemented in contexts such as that of the GA4GH Beacon Project to facilitate responsible data sharing. To this end, we discuss a Data Sharing Privacy Test developed to distinguish degrees of sensitivity within categories of data recognised as ‘sensitive’. Based on this, we propose guidance for determining the level of protection when sharing genomic and health-related data for the Beacon Project and in other international data sharing initiatives

Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma Cells

Bortezomib (Velcade™) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM). Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ∼30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response

CSMET: Comparative Genomic Motif Detection via Multi-Resolution Phylogenetic Shadowing

Functional turnover of transcription factor binding sites (TFBSs), such as whole-motif loss or gain, are common events during genome evolution. Conventional probabilistic phylogenetic shadowing methods model the evolution of genomes only at nucleotide level, and lack the ability to capture the evolutionary dynamics of functional turnover of aligned sequence entities. As a result, comparative genomic search of non-conserved motifs across evolutionarily related taxa remains a difficult challenge, especially in higher eukaryotes, where the cis-regulatory regions containing motifs can be long and divergent; existing methods rely heavily on specialized pattern-driven heuristic search or sampling algorithms, which can be difficult to generalize and hard to interpret based on phylogenetic principles. We propose a new method: Conditional Shadowing via Multi-resolution Evolutionary Trees, or CSMET, which uses a context-dependent probabilistic graphical model that allows aligned sites from different taxa in a multiple alignment to be modeled by either a background or an appropriate motif phylogeny conditioning on the functional specifications of each taxon. The functional specifications themselves are the output of a phylogeny which models the evolution not of individual nucleotides, but of the overall functionality (e.g., functional retention or loss) of the aligned sequence segments over lineages. Combining this method with a hidden Markov model that autocorrelates evolutionary rates on successive sites in the genome, CSMET offers a principled way to take into consideration lineage-specific evolution of TFBSs during motif detection, and a readily computable analytical form of the posterior distribution of motifs under TFBS turnover. On both simulated and real Drosophila cis-regulatory modules, CSMET outperforms other state-of-the-art comparative genomic motif finders

Measures of Association for Identifying MicroRNA-mRNA Pairs of Biological Interest

MicroRNAs are a class of small non-protein coding RNAs that play an important role in the regulation of gene expression. Most studies on the identification of microRNA-mRNA pairs utilize the correlation coefficient as a measure of association. The use of correlation coefficient is appropriate if the expression data are available for several conditions and, for a given condition, both microRNA and mRNA expression profiles are obtained from the same set of individuals. However, there are many instances where one of the requirements is not satisfied. Therefore, there is a need for new measures of association to identify the microRNA-mRNA pairs of interest and we present two such measures. The first measure requires expression data for multiple conditions but, for a given condition, the microRNA and mRNA expression may be obtained from different individuals. The new measure, unlike the correlation coefficient, is suitable for analyzing large data sets which are obtained by combining several independent studies on microRNAs and mRNAs. Our second measure is able to handle expression data that correspond to just two conditions but, for a given condition, the microRNA and mRNA expression must be obtained from the same set of individuals. This measure, unlike the correlation coefficient, is appropriate for analyzing data sets with a small number of conditions. We apply our new measures of association to multiple myeloma data sets, which cannot be analyzed using the correlation coefficient, and identify several microRNA-mRNA pairs involved in apoptosis and cell proliferation