Inhibition of sodium–glucose cotransporter-2 preserves cardiac function during regional myocardial ischemia independent of alterations in myocardial substrate utilization

The goal of the present study was to evaluate the effects of SGLT2i on cardiac contractile function, substrate utilization, and efficiency before and during regional myocardial ischemia/reperfusion injury in normal, metabolically healthy swine. Lean swine received placebo or canagliflozin (300 mg PO) 24 h prior to and the morning of an invasive physiologic study protocol. Hemodynamic and cardiac function measurements were obtained at baseline, during a 30-min complete occlusion of the circumflex coronary artery, and during a 2-h reperfusion period. Blood pressure, heart rate, coronary flow, and myocardial oxygen consumption were unaffected by canagliflozin treatment. Ventricular volumes remained unchanged in controls throughout the protocol. At the onset of ischemia, canagliflozin produced acute large increases in left ventricular end-diastolic and systolic volumes which returned to baseline with reperfusion. Canagliflozin-mediated increases in end-diastolic volume were directly associated with increases in stroke volume and stroke work relative to controls during ischemia. Canagliflozin also increased cardiac work efficiency during ischemia relative to control swine. No differences in myocardial uptake of glucose, lactate, free fatty acids or ketones, were noted between treatment groups at any time. In separate experiments using a longer 60 min coronary occlusion followed by 2 h of reperfusion, canagliflozin increased end-diastolic volume and stroke volume and significantly diminished myocardial infarct size relative to control swine. These data demonstrate that SGLT2i with canagliflozin preserves cardiac contractile function and efficiency during regional myocardial ischemia and provides ischemia protection independent of alterations in myocardial substrate utilization

Gut microbiota utilize immunoglobulin A for mucosal colonization

The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis

Experimental active control of a typical section using a trailing-edge flap

This paper presents an experimental implementation of an active control system used to suppress flutter in a typical section airfoil. The H2 optimal control system design is based on experimental system identifications of the transfer functions between three measured system variables - pitch, plunge, and flap position - and a single control signal that commands the flap of the airfoil. Closed-loop response of the airfoil demonstrated gust alleviation below the open-loop flutter boundary. In addition, the flutter boundary was extended by 12.4% through the application of active control. Cursory robustness tests demonstrate stable control for variations in flow speed of ± 10%

Measurement of a small atmospheric νμ/νe\nu_\mu/\nu_e ratio

From an exposure of 25.5~kiloton-years of the Super-Kamiokande detector, 900 muon-like and 983 electron-like single-ring atmospheric neutrino interactions were detected with momentum $p_e > 100$ MeV/$c$, $p_\mu > 200$ MeV/$c$, and with visible energy less than 1.33 GeV. Using a detailed Monte Carlo simulation, the ratio $(\mu/e)_{DATA}/(\mu/e)_{MC}$ was measured to be $0.61 \pm 0.03(stat.) \pm 0.05(sys.)$, consistent with previous results from the Kamiokande, IMB and Soudan-2 experiments, and smaller than expected from theoretical models of atmospheric neutrino production.Comment: 14 pages with 5 figure

Calibration of Super-Kamiokande Using an Electron Linac

In order to calibrate the Super-Kamiokande experiment for solar neutrino measurements, a linear accelerator (LINAC) for electrons was installed at the detector. LINAC data were taken at various positions in the detector volume, tracking the detector response in the variables relevant to solar neutrino analysis. In particular, the absolute energy scale is now known with less than 1 percent uncertainty.Comment: 24 pages, 16 figures, Submitted to NIM

Constraints on neutrino oscillation parameters from the measurement of day-night solar neutrino fluxes at Super-Kamiokande

A search for day-night variations in the solar neutrino flux resulting from neutrino oscillations has been carried out using the 504 day sample of solar neutrino data obtained at Super-Kamiokande. The absence of a significant day-night variation has set an absolute flux independent exclusion region in the two neutrino oscillation parameter space.Comment: 11 pages, 3 figures, submitted to PRL, single-spacin

Evidence for oscillation of atmospheric neutrinos

We present an analysis of atmospheric neutrino data from a 33.0 kiloton-year (535-day) exposure of the Super-Kamiokande detector. The data exhibit a zenith angle dependent deficit of muon neutrinos which is inconsistent with expectations based on calculations of the atmospheric neutrino flux. Experimental biases and uncertainties in the prediction of neutrino fluxes and cross sections are unable to explain our observation. The data are consistent, however, with two-flavor nu_mu nu_tau oscillations with sin^2(2theta)>0.82 and 5x10^-4 < delta m^2 < 6x10^-3 eV^2 at 90% confidence level.Comment: 9 pages (two-column) with 4 figures. Small corrections to Eqn.4 and Fig.3. Final version to appear in PR

Contribution mapping: a method for mapping the contribution of research to enhance its impact.

Background: At a time of growing emphasis on both the use of research and accountability, it is important for research funders, researchers and other stakeholders to monitor and evaluate the extent to which research contributes to better action for health, and find ways to enhance the likelihood that beneficial contributions are realized. Past attempts to assess research 'impact' struggle with operationalizing 'impact', identifying the users of research and attributing impact to research projects as source. In this article we describe Contribution Mapping, a novel approach to research monitoring and evaluation that aims to assess contributions instead of impacts. The approach focuses on processes and actors and systematically assesses anticipatory efforts that aim to enhance contributions, so-called alignment efforts. The approach is designed to be useful for both accountability purposes and for assisting in better employing research to contribute to better action for health.Methods: Contribution Mapping is inspired by a perspective from social studies of science on how research and knowledge utilization processes evolve. For each research project that is assessed, a three-phase process map is developed that includes the main actors, activities and alignment efforts during research formulation, production and knowledge extension (e.g. dissemination and utilization). The approach focuses on the actors involved in, or interacting with, a research project (the linked actors) and the most likely influential users, who are referred to as potential key users. In the first stage, the investigators of the assessed project are interviewed to develop a preliminary version of the process map and first estimation of research-related contributions. In the second stage, potential key-users and other informants are interviewed to trace, explore and triangulate possible contributions. In the third stage, the presence and role of alignment efforts is analyzed and the preliminary results are shared with relevant stakeholders for feedback and validation. After inconsistencies are clarified or described, the results are shared with stakeholders for learning, improvement and accountability purposes.Conclusion: Contribution Mapping provides an interesting alternative to existing methods that aim to assess research impact. The method is expected to be useful for research monitoring, single case studies, comparing multiple cases and indicating how research can better be employed to contribute to better action for health. © 2012 Kok and Schuit; licensee BioMed Central Ltd