Losartan improves exercise tolerance in patients with diastolic dysfunction and a hypertensive response to exercise

AbstractOBJECTIVESThe aim of the study was to test the hypothesis that angiotensin II (Ang II) blockade would improve exercise tolerance in patients with diastolic dysfunction and a marked increase in systolic blood pressure (SBP) during exercise.BACKGROUNDDiastolic dysfunction may be exacerbated during exercise, especially if there is a marked increase in SBP. Angiotensin II may contribute to the hypertensive response to exercise and impair diastolic performance.METHODSWe performed a randomized, double-blind, placebo-controlled, crossover study of two weeks of losartan (50 mg q.d.) on exercise tolerance and quality of life. The subjects were 20 patients, mean age 64 ± 10 years with normal left ventricular systolic function (EF >50%), no ischemia on stress echocardiogram, mitral flow velocity E/A <1, normal resting SBP (<150 mm Hg), and a hypertensive response to exercise (SBP >200 mm Hg). Exercise echocardiograms (Modified Bruce Protocol) and the Minnesota Living With Heart Failure questionnaire were administered at baseline, and after each two-week treatment period, separated by a two-week washout period.RESULTSResting blood pressure (BP) was unaltered by placebo or losartan. During control, patients were able to exercise for 11.3 ± 2.5 (mean ± SD) min, with a peak exercise SBP of 226 ± 24 mm Hg. After two weeks of losartan, baseline BP was unaltered, but peak SBP during exercise decreased to 193 ± 27 mm Hg (p < 0.05 vs. baseline and placebo), and exercise time increased to 12.3 ± 2.6 min (p < 0.05 vs. baseline and placebo). With placebo, there was no improvement in exercise duration (11.0 ± 2.0 min) or peak exercise SBP (217 ± 26 mm Hg). Quality of life improved with losartan (18 ± 22, p < 0.05) compared to placebo (22 ± 26).CONCLUSIONSIn patients with Doppler evidence of diastolic dysfunction at rest and a hypertensive response to exercise, Ang II receptor blockade blunts the hypertensive response to exercise, increases exercise tolerance and improves quality of life

Rapid communication A rapid and reversible change in dopamine transporters induced by methamphetamine

Abstract Because high doses of methamphetamine promote free radical formation, and striatal dopamine transporters are rapidly inactivated by oxidative events, we determined the effect of a single high dose of methamphetamine on dopamine transporter activity in striatal synaptosomes. One hour after methamphetamine administration, dopamine uptake decreased by 48%. This dramatic decline was totally reversed by 24 h after treatment. These findings suggest that methamphetamine reversibly decreases dopamine transporter activity by oxidative mechanisms

RooStatsCms: a tool for analyses modelling, combination and statistical studies

The RooStatsCms (RSC) software framework allows analysis modelling and combination, statistical studies together with the access to sophisticated graphics routines for results visualisation. The goal of the project is to complement the existing analyses by means of their combination and accurate statistical studies.Comment: Proceedings of the 11th Topical Seminar on Innovative Particle and Radiation Detectors. 4 pages and 5 figure

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

VAST: An ASKAP Survey for Variables and Slow Transients

The Australian Square Kilometre Array Pathfinder (ASKAP) will give us an unprecedented opportunity to investigate the transient sky at radio wavelengths. In this paper we present VAST, an ASKAP survey for Variables and Slow Transients. VAST will exploit the wide-field survey capabilities of ASKAP to enable the discovery and investigation of variable and transient phenomena from the local to the cosmological, including flare stars, intermittent pulsars, X-ray binaries, magnetars, extreme scattering events, interstellar scintillation, radio supernovae and orphan afterglows of gamma ray bursts. In addition, it will allow us to probe unexplored regions of parameter space where new classes of transient sources may be detected. In this paper we review the known radio transient and variable populations and the current results from blind radio surveys. We outline a comprehensive program based on a multi-tiered survey strategy to characterise the radio transient sky through detection and monitoring of transient and variable sources on the ASKAP imaging timescales of five seconds and greater. We also present an analysis of the expected source populations that we will be able to detect with VAST.Comment: 29 pages, 8 figures. Submitted for publication in Pub. Astron. Soc. Australi

Measurements of traffic-dominated pollutant emissions in a Chinese megacity

Direct measurements of NOx, CO and aromatic volatile organic compound (VOC) (benzene, toluene, C2-benzenes and C3-benzenes) flux were made for a central area of Beijing using the eddy-covariance technique. Measurements were made during two intensive field campaigns in central Beijing as part of the Air Pollution and Human Health (APHH) project, the first in November–December 2016 and the second during May–June 2017, to contrast wintertime and summertime emission rates. There was little difference in the magnitude of NOx flux between the two seasons (mean NOx flux was 4.41 mg m−2 h−1 in the winter compared to 3.55 mg m−2 h−1in the summer). CO showed greater seasonal variation, with mean CO flux in the winter campaign (34.7 mg m−2 h−1) being over twice that of the summer campaign (15.2 mg m−2 h−1). Larger emissions of aromatic VOCs in summer were attributed to increased evaporation due to higher temperatures. The largest fluxes in NOx and CO generally occurred during the morning and evening rush hour periods, indicating a major traffic source with high midday emissions of CO, indicating an additional influence from cooking fuel. Measured NOx and CO fluxes were then compared to the MEIC 2013 emissions inventory, which was found to significantly overestimate emissions for this region,providing evidence that proxy-based emissions inventories have positive biases in urban centres. This first set of pollutant fluxes measured in Beijing provides an important benchmark of emissions from the city which can help to inform and evaluate current emissions inventories

Hubble Space Telescope STIS Observations of GRB 000301C: CCD Imaging and Near-Ultraviolet MAMA Spectroscopy

We present Space Telescope Imaging Spectrograph observations of the optical transient (OT) counterpart of the γ-ray burster GRB 000301C obtained 5 days after the burst, on 2000 March 6. CCD clear-aperture imaging reveals a R ≃ 21.50 ± 0.15 source with no apparent host galaxy. An 8000 s, 1150 Å 18 on the line of sight to the OT. This measured redshift is conservatively a lower limit to the GRB redshift. However, as all other GRBs that have deep Hubble Space Telescope images appear to lie on the stellar field of a host galaxy, and as the large H I column density measured here and in later ground-based observations is unlikely on a random line of sight, we believe we are probably seeing absorption from H I in the host galaxy. In any case, this represents the largest direct redshift determination of a γ-ray burster to date. Our data are compatible with an OT spectrum represented by a power law with an intrinsic index α = 1.2 (f_ν ∝ ν^(-α)) and no extinction in the host galaxy, or with α = 0.5 and extinction by SMC-like dust in the OT rest frame with A_V = 0.15. The large N_(H I) and the lack of a detected host are similar to the situation for damped Lyα absorbers at z > 2

Study of Spin and Decay-Plane Correlations of W Bosons in the e+e- -> W+W- Process at LEP

Data collected at LEP at centre-of-mass energies \sqrt(s) = 189 - 209 GeV are used to study correlations of the spin of W bosons using e+e- -> W+W- -> lnqq~ events. Spin correlations are favoured by data, and found to agree with the Standard Model predictions. In addition, correlations between the W-boson decay planes are studied in e+e- -> W+W- -> lnqq~ and e+e- -> W+W- -> qq~qq~ events. Decay-plane correlations, consistent with zero and with the Standard Model predictions, are measured

Ultrarelativistic sources in nonlinear electrodynamics

The fields of rapidly moving sources are studied within nonlinear electrodynamics by boosting the fields of sources at rest. As a consequence of the ultrarelativistic limit the delta-like electromagnetic shock waves are found. The character of the field within the shock depends on the theory of nonlinear electrodynamics considered. In particular, we obtain the field of an ultrarelativistic charge in the Born-Infeld theory.Comment: 10 pages, 3 figure