RNA SILENCING AND HIGHER ORDER CHROMATIN ORGANIZATION IN DROSOPHILA

Higher order chromatin organization influences gene expression, but mechanisms by which this phenomenon occurs are not well understood. RNA silencing, a conserved mechanism that involves small RNAs bound to an Argonaute protein, mediates gene expression via transcriptional or post-transcriptional regulation. Recently, a role for RNA silencing in chromatin has been emerging. In fission yeast, a major role of RNA interference (RNAi) is to establish pericentromeric heterochromatin. However, whether this mechanism is conserved throughout evolution is unclear. In Drosophila, a powerful model organism, there are multiple functionally distinct RNA silencing pathways. Previous studies have suggested the involvement of the Piwi-interacting RNA (piRNA) and endogenous small interfering RNA (endo-siRNA) pathways in heterochromatin formation in order to silence transposable elements in germline and somatic tissues, respectively, but direct evidence is lacking. We addressed whether the genomic locations generating these small RNAs may act as AGO-dependent platforms for heterochromatin recruitment. Our genetic and biochemical analyses revealed that heterochromatin is nucleated independently of endo-siRNA and piRNA pathways suggesting that RNAi-dependent heterochromatin assembly may not be conserved in metazoans. Chromatin insulators are regulatory elements characterized by enhancer blocking and barrier activity. Insulators form large nuclear foci termed insulator bodies that are tethered to the nuclear matrix and have been proposed to organize the genome into distinct transcriptional domains by looping out intervening DNA. In Drosophila, RNA silencing has been reported to affect nuclear organization of gypsy insulator complexes and formation of Polycomb repression bodies. Our studies revealed that AGO2 is required for CTCF/CP190-dependent Fab-8 insulator function independent of its catalytic activity or Dicer-2. Moreover, AGO2 associates with euchromatin but not heterochromatin genome-wide. Also, AGO2 associates physically with CP190 and CTCF, and mutation of CTCF, CP190, or AGO2 decreases chromosomal looping interactions and alters gene expression. We propose a novel RNAi-independent role for AGO2 in the nucleus. We postulate that insulator proteins recruit AGO2 to chromatin to promote or stabilize chromosomal interactions crucial for proper gene expression. Overall, our findings demonstrate novel mechanisms by which RNA silencing affects gene expression on the level of higher order chromatin organization

Sorted-pareto dominance and qualitative notions of optimality

Pareto dominance is often used in decision making to compare decisions that have multiple preference values – however it can produce an unmanageably large number of Pareto optimal decisions. When preference value scales can be made commensurate, then the Sorted-Pareto relation produces a smaller, more manageable set of decisions that are still Pareto optimal. Sorted-Pareto relies only on qualitative or ordinal preference information, which can be easier to obtain than quantitative information. This leads to a partial order on the decisions, and in such partially-ordered settings, there can be many different natural notions of optimality. In this paper, we look at these natural notions of optimality, applied to the Sorted-Pareto and min-sum of weights case; the Sorted-Pareto ordering has a semantics in decision making under uncertainty, being consistent with any possible order-preserving function that maps an ordinal scale to a numerical one. We show that these optimality classes and the relationships between them provide a meaningful way to categorise optimal decisions for presenting to a decision maker

Sleep Duration in Adolescent Girls: Correlates and Association with Obesity Risk

The present study aimed to identify demographic, behavioral, and school-related factors associated with week night sleep duration among an ethnically diverse sample of 582 adolescent girls from the Trial of Activity for Adolescent Girls (TAAG) 2. The distribution of sleep duration categories (9 hours) differed significantly among ethnic groups in bivariate analyses, but not in the final multivariate model. Additionally, sleep duration was negatively associated with distance to school from home, typical time spent on the computer, and school start time. In contrast to previous findings, shortened sleep duration was not associated with increased body mass index (BMI), body fat percentage, or quantity of moderate-to-vigorous physical activity (MVPA). Findings show support for delayed school start times. In addition, future research should examine whether interventions to reduce screen time activities among adolescents is effective in increasing their sleep duration

Energy Aspects in Spray Formation by Homogenous Flash Boiling Process

[EN] When a pressurized bubbly mixture is driven out through an orifice, the mixture pressure abruptly drops and the bubbles undergo a rapid expansion process, which under some circumstances results in a rapid disintegration of the liquid bulk into small droplets (atomization). Depending on the initial conditions, heterogeneous or homogeneous nucleation of vapor bubbles may occur. For homogeneous nucleation, the vapor bubbles grow rapidly one towards the other, and when they touch each other the bubbles “explode”. In this stage, the liquid around the bubbles is teared, and a spray with small and uniform droplets is formed. In the literature, it seems that the efficiency of the homogenous flash boiling process is very low. In this work, we analyse this process and analyse it for possible energy losses.Moshkovich, Y.; Levy, Y.; Sher, I.; Sher, E. (2017). Energy Aspects in Spray Formation by Homogenous Flash Boiling Process. En Ilass Europe. 28th european conference on Liquid Atomization and Spray Systems. Editorial Universitat Politècnica de València. 90-96. https://doi.org/10.4995/ILASS2017.2017.4773OCS909

Rational design of fast boat hull

We present a new method for the rational design of the hull structure of planing boats, which considers hydro-elasticity, structural dynamics and nonlinearity of geometry and material. The method combines rules calculations with analytical expression and analysis of FSI to a practical design procedure. A design example demonstrates a saving of 20% of the bottom plate thickness, relative to design by rules, while keeping the rules allowable stress. Exceeding the rules allowable stresses enables further reduction of weight. We designed and constructed a full scale research boat and held sea trials, measuring strains at high sampling rate. Our research boat has two sides of different construction: the port side is designed by rules, while the starboard side is designed by our rational design method, with 20% thinner plates and double spacing between the longitudinal stiffeners. We present a verification of our design method: A comparison of stresses between design by rules, rational design, and measurements in the sea trials shows: For the heavy side (designed by rules), rules, rational, and trials show similar stresses, so both rules and rational are applicable for design; While for the light side (rational design), the rules dramatically over assess the stresses, while rational and trials show good agreement. We therefore expect this study to advance the design practice, to obtain more efficient boats

E-Commerce and the Undergraduate MIS Curricula: an Exploratory Study

Undergraduate MIS curricula should reflect the popularity of e-commerce technologies in business practices. The study analyzes current trends of incorporating e-commerce content and skills into the undergraduate MIS curricula of AACSB accredited business schools. A definite trend to incorporate e-commerce knowledge and skills into the elective component of undergraduate MIS programs was found. Problems identified and possible solutions are discussed

Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugs.

BACKGROUND: Needle syringe programmes and opioid substitution therapy for preventing hepatitis C transmission in people who inject drugsNeedle syringe programmes (NSP) and opioid substitution therapy (OST) are the primary interventions to reduce hepatitis C (HCV) transmission in people who inject drugs. There is good evidence for the effectiveness of NSP and OST in reducing injecting risk behaviour and increasing evidence for the effectiveness of OST and NSP in reducing HIV acquisition risk, but the evidence on the effectiveness of NSP and OST for preventing HCV acquisition is weak. OBJECTIVES: To assess the effects of needle syringe programmes and opioid substitution therapy, alone or in combination, for preventing acquisition of HCV in people who inject drugs. SEARCH METHODS: We searched the Cochrane Drug and Alcohol Register, CENTRAL, the Cochrane Database of Systematic Reviews (CDSR), the Database of Abstracts of Reviews of Effects (DARE), the Health Technology Assessment Database (HTA), the NHS Economic Evaluation Database (NHSEED), MEDLINE, Embase, PsycINFO, Global Health, CINAHL, and the Web of Science up to 16 November 2015. We updated this search in March 2017, but we have not incorporated these results into the review yet. Where observational studies did not report any outcome measure, we asked authors to provide unpublished data. We searched publications of key international agencies and conference abstracts. We reviewed reference lists of all included articles and topic-related systematic reviews for eligible papers. SELECTION CRITERIA: We included prospective and retrospective cohort studies, cross-sectional surveys, case-control studies and randomised controlled trials that measured exposure to NSP and/or OST against no intervention or a reduced exposure and reported HCV incidence as an outcome in people who inject drugs. We defined interventions as current OST (within previous 6 months), lifetime use of OST and high NSP coverage (regular attendance at an NSP or all injections covered by a new needle/syringe) or low NSP coverage (irregular attendance at an NSP or less than 100% of injections covered by a new needle/syringe) compared with no intervention or reduced exposure. DATA COLLECTION AND ANALYSIS: We followed the standard Cochrane methodological procedures incorporating new methods for classifying risk of bias for observational studies. We described study methods against the following 'Risk of bias' domains: confounding, selection bias, measurement of interventions, departures from intervention, missing data, measurement of outcomes, selection of reported results; and we assigned a judgment (low, moderate, serious, critical, unclear) for each criterion. MAIN RESULTS: We identified 28 studies (21 published, 7 unpublished): 13 from North America, 5 from the UK, 4 from continental Europe, 5 from Australia and 1 from China, comprising 1817 incident HCV infections and 8806.95 person-years of follow-up. HCV incidence ranged from 0.09 cases to 42 cases per 100 person-years across the studies. We judged only two studies to be at moderate overall risk of bias, while 17 were at serious risk and 7 were at critical risk; for two unpublished datasets there was insufficient information to assess bias. As none of the intervention effects were generated from RCT evidence, we typically categorised quality as low. We found evidence that current OST reduces the risk of HCV acquisition by 50% (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.40 to 0.63, I(2) = 0%, 12 studies across all regions, N = 6361), but the quality of the evidence was low. The intervention effect remained significant in sensitivity analyses that excluded unpublished datasets and papers judged to be at critical risk of bias. We found evidence of differential impact by proportion of female participants in the sample, but not geographical region of study, the main drug used, or history of homelessness or imprisonment among study samples.Overall, we found very low-quality evidence that high NSP coverage did not reduce risk of HCV acquisition (RR 0.79, 95% CI 0.39 to 1.61) with high heterogeneity (I(2) = 77%) based on five studies from North America and Europe involving 3530 participants. After stratification by region, high NSP coverage in Europe was associated with a 76% reduction in HCV acquisition risk (RR 0.24, 95% CI 0.09 to 0.62) with less heterogeneity (I(2) =0%). We found low-quality evidence of the impact of combined high coverage of NSP and OST, from three studies involving 3241 participants, resulting in a 74% reduction in the risk of HCV acquisition (RR 0.26 95% CI 0.07 to 0.89). AUTHORS' CONCLUSIONS: OST is associated with a reduction in the risk of HCV acquisition, which is strengthened in studies that assess the combination of OST and NSP. There was greater heterogeneity between studies and weaker evidence for the impact of NSP on HCV acquisition. High NSP coverage was associated with a reduction in the risk of HCV acquisition in studies in Europe

Electrode roughness dependent electrodeposition of sodium at the nanoscale

Na metal is an attractive anode material for rechargeable Na ion batteries, however, the dendritic growth of Na can cause serious safety issues. Along with modifications of solid-electrolyte interphase (SEI), engineering the electrode has been reported to be effective in suppressing Na dendritic growth, likely by reducing localized current density accumulation. However, fundamental understanding of Na growth at the nanoscale is still limited. Here, we report an in-situ study of Na electrodeposition in electrochemical liquid cells with the electrodes in different surface roughness, e.g., flat or sharp curvature. Real time observation using transmission electron microscopy (TEM) reveals the Na electrodeposition with remarkable details. Relatively large Na grains (in the micrometer scale) are achieved on the flat electrode surface. The local SEI thickness variations impact the growth rate, thus the morphology of individual grains. In contrast, small Na grains (in tens of nanometers) grow explosively on the electrode at the point with sharp curvature. The newly formed Na grains preferentially deposit at the base of existing grains close to the electrode. Further studies using continuum-based computational modeling suggest that the growth mode of an alkali metal (e.g. Na) is strongly influenced by the transport properties of SEI. Our direct observation of Na deposition in combination with the theoretical modeling provides insights for comprehensive understanding of electrode roughness and SEI effects on Na electrochemical deposition