66 research outputs found
Revisiting the Local Scaling Hypothesis in Stably Stratified Atmospheric Boundary Layer Turbulence: an Integration of Field and Laboratory Measurements with Large-eddy Simulations
The `local scaling' hypothesis, first introduced by Nieuwstadt two decades
ago, describes the turbulence structure of stable boundary layers in a very
succinct way and is an integral part of numerous local closure-based numerical
weather prediction models. However, the validity of this hypothesis under very
stable conditions is a subject of on-going debate. In this work, we attempt to
address this controversial issue by performing extensive analyses of turbulence
data from several field campaigns, wind-tunnel experiments and large-eddy
simulations. Wide range of stabilities, diverse field conditions and a
comprehensive set of turbulence statistics make this study distinct
Phenotypic and pharmacogenetic evaluation of patients with thiazide-induced hyponatremia.
Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide-induced hyponatremia (TIH), a clinically significant adverse effect, is poorly understood. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with TIH. In a cohort of 109 TIH patients, those with severe TIH displayed an extended phenotype of intravascular volume expansion, increased free water reabsorption, urinary prostaglandin E2 excretion, and reduced excretion of serum chloride, magnesium, zinc, and antidiuretic hormone. GWAS in a separate cohort of 48 TIH patients and 2,922 controls from the 1958 British birth cohort identified an additional 14 regions associated with TIH. We identified a suggestive association with a variant in SLCO2A1, which encodes a prostaglandin transporter in the distal nephron. Resequencing of SLCO2A1 revealed a nonsynonymous variant, rs34550074 (p.A396T), and association with this SNP was replicated in a second cohort of TIH cases. TIH patients with the p.A396T variant demonstrated increased urinary excretion of prostaglandin E2 and metabolites. Moreover, the SLCO2A1 phospho-mimic p.A396E showed loss of transporter function in vitro. These findings indicate that the phenotype of TIH involves a more extensive metabolic derangement than previously recognized. We propose one mechanism underlying TIH development in a subgroup of patients in which SLCO2A1 regulation is altered.This work was supported by an Academy of Medical Sciences grant for clinical lecturers (to JSW and
MG), British Heart Foundation grant PG/09/089 (to KMO), the
National Institute for Health Research (NIHR) Royal Brompton
Cardiovascular Biomedical Research Unit (to JSW and SC), the
Fondation Leducq (to JSW and SC), and the British Heart Foundation (to JSW and SC). MDT holds a Medical Research Council
Senior Clinical Fellowship (G0902313). This work was supported
by the Medical Research Council (grant numbers G510364 and
G1000861). This research used the ALICE and SPECTRE High
Performance Computing Facilities at the University of Leicester
Fire-Related Carbon Emissions from Land Use Transitions in Southern Amazonia
Various land-use transitions in the tropics contribute to atmospheric carbon emissions, including forest conversion for small-scale farming, cattle ranching, and production of commodities such as soya and palm oil. These transitions involve fire as an effective and inexpensive means for clearing. We applied the DECAF (DEforestation CArbon Fluxes) model to Mato Grosso, Brazil to estimate fire emissions from various land-use transitions during 2001-2005. Fires associated with deforestation contributed 67 Tg C/yr (17 and 50 Tg C/yr from conversion to cropland and pasture, respectively), while conversion of savannas and existing cattle pasture to cropland contributed 17 Tg C/yr and pasture maintenance fires 6 Tg C/yr. Large clearings (>100 ha/yr) contributed 67% of emissions but comprised only 10% of deforestation events. From a policy perspective, results imply that intensification of agricultural production on already-cleared land and policies to discourage large clearings would reduce the major sources of emissions from fires in this region. Copyright 2008 by the American Geophysical Union
Structural studies of T4S systems by electron microscopy
Abstract: Type IV secretion (T4S) systems are large dynamic nanomachines that transport DNA and/or proteins through the membranes of bacteria. Analysis of T4S system architecture is an extremely challenging task taking into account their multi protein organisation and lack of overall global symmetry. Nonetheless the last decade demonstrated an amazing progress achieved by X-ray crystallography and cryo-electron microscopy. In this review we present a structural analysis of this dynamic complex based on recent advances in biochemical, biophysical and structural studies
Comparison of diagnostic guidelines for juvenile bipolar disorder
The purpose of the present paper was to compare currently available diagnostic guidelines for juvenile bipolar disorder with respect to utility in research and clinical practice. A systematic search of psychiatric, medical and psychological databases was conducted using the terms 'juvenile bipolar disorder', 'paediatric bipolar disorder' and 'guidelines'. Three main sets of guidelines issued by the National Institute of Health and Clinical Excellence (UK), The National Institute of Mental Health (USA) and Child Psychiatric Workshop (USA) were found. There were key differences in the recommendations made by each regarding the diagnosis and symptomatic presentation of juvenile bipolar disorder. Although the diagnosis of juvenile bipolar disorder is gaining increased recognition, its definition remains controversial. It is recommended that clinicians and researchers need to develop diagnostic guidelines that have clinical salience and can be used for future research by incorporating key features of those that are currently available
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