Regulation of KCa2.3 andendothelium-dependent hyperpolarization (EDH) in the rat middle cerebral artery: the role of lipoxygenase metabolites and isoprostanes

Background and Purpose. In rat middle cerebral arteries, endothelium-dependent hyperpolarization (EDH) is mediated by activation of calcium-activated potassium(KCa) channels specifically KCa2.3 and KCa3.1. Lipoxygenase (LOX) products function as endothelium-derived hyperpolarizing factors (EDHFs) in rabbit arteries by stimulating KCa2.3. We investigated if LOX products contribute to EDH in rat cerebral arteries. Methods. Arachidonic acid (AA) metabolites produced in middle cerebral arteries were measured using HPLC and LC/MS. Vascular tension and membrane potential responses to SLIGRL were simultaneously recorded using wire myography and intracellular microelectrodes. Results. SLIGRL, an agonist at PAR2 receptors, caused EDH that was inhibited by a combination of KCa2.3 and KCa3.1 blockade. Non-selective LOX-inhibition reduced EDH, whereas inhibition of 12-LOX had no effect. Soluble epoxide hydrolase (sEH) inhibition enhanced the KCa2.3 component of EDH. Following NO synthase (NOS) inhibition, the KCa2.3 component of EDH was absent. Using HPLC, middle cerebral arteries metabolized 14C-AA to 15- and 12-LOX products under control conditions. With NOS inhibition, there was little change in LOX metabolites, but increased F-type isoprostanes. 8-iso-PGF2α inhibited the KCa2.3 component of EDH. Conclusions. LOX metabolites mediate EDH in rat middle cerebral arteries. Inhibition of sEH increases the KCa2.3 component of EDH. Following NOS inhibition,loss of KCa2.3 function is independent of changes in LOX production or sEH inhibition but due to increased isoprostane production and subsequent stimulation of TP receptors. These findings have important implications in diseases associated with loss of NO signaling such as stroke; where inhibition of sEH and/or isoprostane formation may of benefit

Pensions 4-2 au Québec : Vers un nouveau partenariat

Les Québécois ayant des revenus de 40 000 $ et moins, et ayant contribué au RRQ toute leur carrière, sont généralement bien couvert par les programmes de revenus de retraite actuellement en vigueur, lesquels sont aussi présentés comme les Piliers I et II des systèmes de pension québécois et canadien. Moins bien couverts sont les travailleurs du secteur privé avec des revenus dépassant les 40 000 dollars qui ne font pas partie d’un régime de pension d’employeur. Leur nombre serait de l’ordre de 800 000 travailleurs. Les enjeux auxquels font face ces travailleurs sont d’autant plus grands que la réalité financière indique que l’épargne doit commencer lorsque l’on est jeune pour avoir un effet tangible sur les revenus à la retraite. Toutefois, cette réalité incontournable de la planification financière se confronte aux besoins et exigences de la vie pratique au jour le jour. À trente ans, les soucis reliés à la retraite sont moins pressants que le développement de sa carrière, l’établissement et le support d’une famille et le maintien d’un style général de vie approprié selon ses revenus présents et attendus. Dans ce contexte, il est probablement trop optimiste de présumer que des décisions rationnelles et optimales d’épargne soient effectivement prises. Par contre, l’objectif d’épargner en vue de la retraite demeure important. En effet, l’espérance de vie augmente et ce phénomène entraîne non seulement une période plus longue à financer pour la retraite mais aussi une augmentation potentielle de dépenses médicales, avec la crainte que certaines ne soient pas complètement prises en charge par le système de santé public. Les Québécois sont-ils prêts à faire face à une telle éventualité? L’objectif principal de ce rapport est de proposer des mécanismes à travers lesquels les Québécois sont encouragés à épargner davantage. Ceux-ci sont regroupés sous le titre général de Pensions 4-2., Pensions, REER,financement retraite

Dynamic interactions between the ground heat exchanger and environments in earth–air tunnel ventilation of buildings

Earth–air tunnel ventilation is an energy efficient method of preheating or cooling of supply air to abuilding. The purposes of this study are to investigate the performance of earth–air heat exchangersunder varying soil and atmosphere conditions and the interactions between the heat exchanger andenvironments. A computer program has been developed for simulation of the thermal performance of anearth–air heat exchanger for preheating and cooling of supply air, taking account of dynamic variationsof climatic, load and soil conditions. The program solves equations for coupled heat and moisture transferin soil with boundary conditions for convection, radiation and evaporation/condensation that vary withthe climate both at the soil top surface and inside the heat exchanger. The importance of dynamic inter-actions between the heat exchanger, soil and atmosphere is illustrated from the comparison of the heattransfer rates through the heat exchanger. The predicted heat transfer rate varies with operating time anddecreases along the passage of air in the heat exchanger. Neglecting the interactions would significantlyover-predict the heat transfer rate and the amount of over-prediction increases with operating time

Serious gaming and gamification education in health professions: Systematic review

Background: There is a worldwide shortage of health workers, and this issue requires innovative education solutions. Serious gaming and gamification education have the potential to provide a quality, cost-effective, novel approach that is flexible, portable, and enjoyable and allow interaction with tutors and peers. Objective: The aim of this systematic review was to evaluate the effectiveness of serious gaming/gamification for health professions education compared with traditional learning, other types of digital education, or other serious gaming/gamification interventions in terms of patient outcomes, knowledge, skills, professional attitudes, and satisfaction (primary outcomes) as well as economic outcomes of education and adverse events (secondary outcomes). Methods: A comprehensive search of MEDLINE, EMBASE, Web of Knowledge, Educational Resources Information Centre, Cochrane Central Register of Controlled Trials, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature was conducted from 1990 to August 2017. Randomized controlled trials (RCTs) and cluster RCTs were eligible for inclusion. Two reviewers independently searched, screened, and assessed the study quality and extracted data. A meta-analysis was not deemed appropriate due to the heterogeneity of populations, interventions, comparisons, and outcomes. Therefore, a narrative synthesis is presented. Results: A total of 27 RCTs and 3 cluster RCTs with 3634 participants were included. Two studies evaluated gamification interventions, and the remaining evaluated serious gaming interventions. One study reported a small statistically significant difference between serious gaming and digital education of primary care physicians in the time to control blood pressure in a subgroup of their patients already taking antihypertensive medications. There was evidence of a moderate-to-large magnitude of effect from five studies evaluating individually delivered interventions for objectively measured knowledge compared with traditional learning. There was also evidence of a small-to-large magnitude of effect from 10 studies for improved skills compared with traditional learning. Two and four studies suggested equivalence between interventions and controls for knowledge and skills, respectively. Evidence suggested that serious gaming was at least as effective as other digital education modalities for these outcomes. There was insufficient evidence to conclude whether one type of serious gaming/gamification intervention is more effective than any other. There was limited evidence for the effects of serious gaming/gamification on professional attitudes. Serious gaming/gamification may improve satisfaction, but the evidence was limited. Evidence was of low or very low quality for all outcomes. Quality of evidence was downgraded due to the imprecision, inconsistency, and limitations of the study. Conclusions: Serious gaming/gamification appears to be at least as effective as controls, and in many studies, more effective for improving knowledge, skills, and satisfaction. However, the available evidence is mostly of low quality and calls for further rigorous, theory-driven research

Dynamics of membranes driven by actin polymerization

A motile cell, when stimulated, shows a dramatic increase in the activity of its membrane, manifested by the appearance of dynamic membrane structures such as lamellipodia, filopodia and membrane ruffles. The external stimulus turns on membrane bound activators, like Cdc42 and PIP2, which cause increased branching and polymerization of the actin cytoskeleton in their vicinity leading to a local protrusive force on the membrane. The emergence of the complex membrane structures is a result of the coupling between the dynamics of the membrane, the activators and the protrusive forces. We present a simple model that treats the dynamics of a membrane under the action of actin polymerization forces that depend on the local density of freely diffusing activators on the membrane. We show that, depending on the spontaneous membrane curvature associated with the activators, the resulting membrane motion can be wave-like, corresponding to membrane ruffling and actin-waves, or unstable, indicating the tendency of filopodia to form. Our model also quantitatively explains a variety of related experimental observations and makes several testable predictions.Comment: 37 pages, 8 figures, revte

Bird Migration Routes and Risk for Pathogen Dispersion into Western Mediterranean Wetlands

Migratory movements of wild birds likely spread zoonotic infectious agents, such as avian influenza and West Nile viruses

Designing Research

The aim of this chapter is to set out a process that researchers can follow to design a robust quantitative research study of occupant behavior in buildings. Central to this approach is an emphasis on intellectual clarity around what is being measured and why. To help achieve this clarity, researchers are encouraged to literally draw these relationships out in the form of a concept map capturing the theoretical model of the cause and effect between occupant motivations and energy use. Having captured diagrammatically how the system is thought to work, the next step is to formulate research questions or hypotheses capturing the relationship between variables in the theoretical model, and to start to augment the diagram with the measurands (things that can actually be measured) that are good proxies for each concept. Once these are identified, the diagram can be further augmented with one or more methods of measuring each measurand. The chapter argues that it is necessary to carefully define concepts and their presumed relationships, and to clearly state research questions and identify what the researcher intends to measure before starting data collection. The chapter also explains the ideas of reliability, validity, and uncertainty, and why knowledge about them is essential for any researcher

A Crosslinking Analysis of GAP-43 Interactions with Other Proteins in Differentiated N1E-115 Cells

It has been suggested that GAP-43 (growth-associated protein) binds to various proteins in growing neurons as part of its mechanism of action. To test this hypothesis in vivo, differentiated N1E-115 neuroblastoma cells were labeled with [35S]-amino acids and were treated with a cleavable crosslinking reagent. The cells were lysed in detergent and the lysates were centrifuged at 100,000 × g to isolate crosslinked complexes. Following cleavage of the crosslinks and analysis by two-dimensional gel electrophoresis, it was found that the crosslinker increased the level of various proteins, and particularly actin, in this pellet fraction. However, GAP-43 was not present, suggesting that GAP-43 was not extensively crosslinked to proteins of the cytoskeleton and membrane skeleton and did not sediment with them. GAP-43 also did not sediment with the membrane skeleton following nonionic detergent lysis. Calmodulin, but not actin or other proposed interaction partners, co-immunoprecipitated with GAP-43 from the 100,000 × g supernatant following crosslinker addition to cells or cell lysates. Faint spots at 34 kDa and 60 kDa were also present. Additional GAP-43 was recovered from GAP-43 immunoprecipitation supernatants with anti-calmodulin but not with anti-actin. The results suggest that GAP-43 is not present in complexes with actin or other membrane skeletal or cytoskeletal proteins in these cells, but it is nevertheless possible that a small fraction of the total GAP-43 may interact with other proteins