380 research outputs found
Leading Quenching Effects in the Proton Magnetic Moment
We present the first investigation of the extrapolation of quenched nucleon
magnetic moments in quenched chiral effective field theory. We utilize
established techniques in finite-range regularisation and compare with standard
dimensional regularisation methods. Finite-volume corrections to the relevant
loop integrals are also addressed. Finally, the contributions of dynamical sea
quarks to the proton moment are estimated using a recently discovered
phenomenological link between quenched and physical QCD.Comment: 9 pages, 11 figs; v2: revised finite volume discussio
GABAA Receptor Trafficking-Mediated Plasticity of Inhibitory Synapses
Proper developmental, neural cell-type-specific, and activity-dependent regulation of GABAergic transmission is essential for virtually all aspects of CNS function. The number of GABAA receptors in the postsynaptic membrane directly controls the efficacy of GABAergic synaptic transmission. Thus, regulated trafficking of GABAA receptors is essential for understanding brain function in both health and disease. Here we summarize recent progress in the understanding of mechanisms that allow dynamic adaptation of cell surface expression and postsynaptic accumulation and function of GABAA receptors. This includes activity-dependent and cell-type-specific changes in subunit gene expression, assembly of subunits into receptors, as well as exocytosis, endocytic recycling, diffusion dynamics, and degradation of GABAA receptors. In particular, we focus on the roles of receptor-interacting proteins, scaffold proteins, synaptic adhesion proteins, and enzymes that regulate the trafficking and function of receptors and associated proteins. In addition, we review neuropeptide signaling pathways that affect neural excitability through changes in GABAAR trafficking
P-274: Activated endothelin system in polyglobulia
The role of the endothelin system, the functional counterpart of NO, in the pathophysiology of polyglobulia remains still elusive. Therefore a novel erythropoietin overexpressing mouse was generated, with hematocrit levels of about 80%. Hence, we analyzed vascular contractions to ET-1 and big endothelin-1 (big ET-1), endothelin-1 (ET-1) promoter activity, ET-1 immunochemistry, endothelin-1 (ET-1)-protein tissue levels, ETA/B-receptor mRNA expression in this novel transgenic model of severe polyglobulia. For analysis of ET-1 promotor activity, EPO transgenic mice were mated with homozygous transgenic mice expressing the lacZ gene under control of the human ET-1 promoter and immunochistochemistry for gal blue was performed in lacZ transgenic animals. Notwithstanding markedly increased eNOS expression, NO-mediated endothelium-dependent relaxation and circulating and vascular tissue NO levels indicating enhanced bioavailability of NO, ET-1 tissue levels were also augmented in heart, kidney, liver and aorta (2.2±0.3 vs. 0.5±0.1 pg/mg tissue; P<0.01) of transgenic polyglobulic animals. Accordingly, immunohistochemistry demonstrated enhanced expression of ET-1 protein in the vascular wall of polyglobulic animals as compared to controls (p< 0.05), while increase of ET-1 promoter activity was confined to the perivascular tissue (P<0.05). NOS inhibition with L-NAME unmasked increased vascular reactivity to ET-1 and bigET-1 and aortic ETA/B receptor mRNA gene expression was enhanced (p<0.05 vs. controls). Administration of the NOS inhibitor L-NAME led to acute vasoconstriction of peripheral resistance vessels, hypertension and death of transgenic mice within 2 days, while wildtypes did not show increased mortality. Treatment with the ETA antagonist darusentan doubled survival time of transgenic polyglobulic mice after NO synthase inhibition (p<0.01 vs placebo). In conclusion, in this study we provide first evidence that the tissue endothelin system is activated by polyglobulia. Together with a stimulated NO system it contributes to cardiovascular regulation in pathophysiological conditions associated with increased hematocri
Quenching Effects in the Hadron Spectrum
Lattice QCD has generated a wealth of data in hadronic physics over the last
two decades. Until relatively recently, most of this information has been
within the "quenched approximation" where virtual quark--anti-quark pairs are
neglected. This review presents a descriptive discussion of the effects of
removing this approximation in the calculation of hadronic masses.Comment: To appear in "Lattice Hadron Physics", ed. A.C. Kalloniatis, D.B.
Leinweber and A.G. William
OR-53: HMG-CoA reductase inhibitor improves endothelial dysfunction in mineralocorticoid hypertension by inhibition of RhoA
Statins reduce cardiovascular morbidity and mortality. These beneficial effects are not fully explained by their lipid-lowering action. As such, we investigated the impact of a new statin, rosuvastatin, on endothelial function, the key event in early atherogenesis, in an experimental model of normocholesterolemic hypertension. Hypertension was induced in Wistar-Kyoto rats by inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) with Glycyrrhizic acid (GA). 11β-HSD2 provides mineralocorticoid receptor specificity for aldosterone by metabolising glucocorticoids to their receptor inactive 11-dehydro derivatives. GA was added to the drinking water (3 g/L) for 21 days. From days 8 to 21 rosuvastatin (20 mg/kg/d) or placebo were added to chow. Endothelium-dependent and -independent relaxation of isolated aortic rings to acetylcholine (ACh, 10-10-10-5 mol/L) and sodium nitroprusside (SNP, 10-10-10-5 mol/L) was measured. In addition, vascular reactivity to endothelin-1 (ET-1; 10-10-10-7 mol/L) was investigated. ETA and ETB receptor mRNA expression was determined by RT-PCR and RhoA activity by a pull-down assay. Systolic blood pressure increased in rats treated with GA (175 vs 153 mmHg in controls; p<0.01). Endothelium-dependent relaxations to acetylcholine were blunted after GA treatment (p≤0.005 vs control), while the responses to SNP remained unchanged. Rosuvastatin normalized NO-mediated endothelium-dependent relaxation in hypertensive animals (p≤0.01 vs placebo), although blood pressure and cholesterol levels were not affected by the statin. Vascular reactivity to ET-1 was increased by GA (p<0.01 vs control), but not affected by rosuvastatin. ETB receptor mRNA decreased in the GA group (p<0.05 vs control) and was upregulated by rosuvastatin (p<0.005; GA+rosuvastatin vs GA), whereas ETA receptor mRNA upregulation in the GA group (p<0.01 vs control) was partially prevented by the statin. In addition, GA increased Rho-GTP binding (p≤0.05 vs control) which was prevented in both groups by rosuvastatin treatment (p≤0.01 control+rosuvastatin vs control and GA+rosuvastatin vs GA). These data for the first time show that HMG-CoA inhibition improves endothelial dysfunction in normocholesterolemic mineralocorticoid hypertension without affecting blood pressure or cholesterol levels by correction of a stimulated endothelin syste
P-341: Selective COX-2 inhibitors and renal injury in salt-sensitive hypertension
Renal safety of selective COX-2 inhibitors (coxibs) is a matter of ongoing discussion. Therefore, in the present study we examined the effects of two different coxibs, celecoxib and rofecoxib, compared to a traditional NSAID, diclofenac, and placebo in salt-sensitive hypertension. Salt-sensitive (DS) and salt-resistant (DR) Dahl rats were fed with NaCl enriched diet (4% NaCl) for 8 weeks. Diclofenac (DS-diclofenac), rofecoxib (DS-rofecoxib), celecoxib (DS-celecoxib) or placebo were added to chow from week 6 to 8. Immunostaining for monocytes/macrophages (ED1) and cytotoxic T-lymphocytes (CD8) was performed. In addition, renal morphology and proteinuria were assessed. COX-2 protein and mRNA were isolated from renal cortex. Untreated hypertensive animals showed preglomerular and glomerular injury including endothelial activation/proliferation, broadened adventitia, collapsing glomerulopathy, mesangial sclerosis, mesangiolysis, extracapillary proliferation, protein drops and especially high grade of glomerulosclerosis (p<0.05 vs DR-placebo) and CD8 and ED1 positive cells (p<0.01 vs DR-placebo) which was improved by celecoxib but not by diclofenac and rofecoxib. Proteinuria was observed in hypertensive animals (p<0.0001 vs DR-placebo), normalised by celecoxib (p=0.0015 vs DS-placebo) and increased by rofecoxib (p<0.05 vs DS-placebo). COX-2 protein and mRNA levels were comparable in all groups. Renal function and morphology improves after celecoxib but not after rofecoxib or diclofenac. This head-to-head comparison demonstrates differential effects of coxibs on renal morphology and function in salt-dependent hypertensio
Pseudo-random number generators for Monte Carlo simulations on Graphics Processing Units
Basic uniform pseudo-random number generators are implemented on ATI Graphics
Processing Units (GPU). The performance results of the realized generators
(multiplicative linear congruential (GGL), XOR-shift (XOR128), RANECU, RANMAR,
RANLUX and Mersenne Twister (MT19937)) on CPU and GPU are discussed. The
obtained speed-up factor is hundreds of times in comparison with CPU. RANLUX
generator is found to be the most appropriate for using on GPU in Monte Carlo
simulations. The brief review of the pseudo-random number generators used in
modern software packages for Monte Carlo simulations in high-energy physics is
present.Comment: 31 pages, 9 figures, 3 table
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