Galilean symmetry in noncommutative field theory

When the interaction potential is suitably reordered, the Moyal field theory admits two types of Galilean symmetries, namely the conventional mass-parameter-centrally-extended one with commuting boosts, but also the two-fold centrally extended ``exotic'' Galilean symmetry, where the commutator of the boosts yields the noncommutative parameter. In the free case, one gets an ``exotic'' two-parameter central extension of the Schroedinger group. The conformal symmetry is, however, broken by the interaction.Comment: Corrected version. Further remarks and references added. LaTex, 8 pages, no figure

Galilean noncommutative gauge theory: symmetries & vortices

Noncommutative Chern-Simons gauge theory coupled to nonrelativistic scalars or spinors is shown to admit the ``exotic'' two-parameter-centrally extended Galilean symmetry, realized in a unique way consistent with the Seiberg-Witten map. Nontopological spinor vortices and topological external-field vortices are constructed by reducing the problem to previously solved self-dual equations.Comment: Updated version: some statements rephrased and further references added. LaTex, 17 pages, no figure

Oral Carnosine Supplementation Prevents Vascular Damage in Experimental Diabetic Retinopathy

Backgrounds/Aims: Pericyte loss, vasoregression and neuroglial activation are characteristic changes in incipient diabetic retinopathy. In this study, the effect of the antioxidant and antiglycating dipeptide carnosine was studied on the development of experimental diabetic retinopathy. Materials/Methods: STZ-induced diabetic Wistar rats were orally treated with carnosine (1g/kg body weight/day). Retinal vascular damage was assessed by quantitative morphometry. Retinal protein extracts were analyzed for markers of oxidative stress, AGE-formation, activation of the hexosamine pathway and changes in the expression of Ang-2, VEGF and heat shock proteins Hsp27 and HO-1. Glial cell activation was analyzed using Western blot analysis and immunofluorescence of GFAP expression and retinal neuronal damage was histologically examined. Results: Oral carnosine treatment prevented retinal vascular damage after 6 months of experimental hyperglycemia. The protection was not caused by ROS-or AGE-inhibition, but associated with a significant induction of Hsp27 in activated glial cells and normalization of increased Ang-2 levels in diabetic retinas. A significant reduction of photoreceptors in retinas of carnosine treated animals was noted. Conclusion: Oral carnosine treatment protects retinal capillary cells in experimental diabetic retinopathy, independent of its biochemical function. The vasoprotective effect of carnosine might be mediated by the induction of protective Hsp27 in activated glial cells and normalization of hyperglycemia-induced Ang-2. Copyright (C) 2011 S. Karger AG, Basel</p

Penetration of topical diclofenac into synovial tissue and fluid of osteoarthritic knees: a multicenter, randomized, placebo-controlled, pharmacokinetic study

Funder: GSK Consumer Healthcare S.A., Nyon, SwitzerlandBackground:: Topical diclofenac, a nonsteroidal anti-inflammatory drug, has proven efficacy and safety in the management of osteoarthritis pain. We investigated penetration of topical diclofenac into knee synovial tissue and fluid (primary objective) and evaluated relative exposure in the knee versus plasma (secondary objective). Methods:: In this phase I, double-blind, multicenter study, patients scheduled for arthroplasty for end-stage knee osteoarthritis were randomly assigned 2:1 to 4 g diclofenac diethylamine 2.32% w/w gel (92.8 mg diclofenac diethylamine, equivalent to 74.4 mg diclofenac, per application) or placebo gel, applied to the affected knee by a trained nurse/designee every 12 h for 7 days before surgery. Diclofenac concentrations were measured in synovial tissue, synovial fluid and plasma from samples obtained during surgery ⩾12 h after last application. Treatment-emergent adverse events (TEAEs) were evaluated. Results:: Evaluable synovial tissue or fluid samples were obtained from 45 (diclofenac n = 29; placebo n = 16) of 47 patients. All diclofenac-treated participants had measurable diclofenac concentrations in synovial tissue [geometric mean 1.57 (95% confidence interval (CI) 1.12, 2.20) ng/g] and fluid [geometric mean 2.27 (95% CI 1.87, 2.76) ng/ml] ⩾12 h after the last dose. Geometric mean (95% CI) ratio of diclofenac in synovial tissue:plasma was 0.32 (0.23, 0.45) and in synovial fluid:plasma was 0.46 (0.40, 0.54). TEAE rates were similar for diclofenac (55.2%) and placebo (58.8%); none were treatment related. Conclusions:: Topical diclofenac diethylamine 2.32% w/w gel penetrated into the osteoarthritic knee after repeated application and remained detectable in synovial tissue and fluid at the end of the final 12 h dosing cycle

Comparison of gait, functional activities and patient-reported outcome measures in patients with knee osteoarthritis and healthy adults using 3D motion analysis and activity monitoring: An exploratory case-control analysis

Objective: To examine functional performance differences using kinematic and kinetic analysis between participants with and without knee osteoarthritis (OA) to determine which outcomes best characterize persons with and without knee OA. Methods: Participants with unilateral moderate knee OA (Kellgren–Lawrence grades 2 or 3) and controls without knee pain were matched for age, gender, and body mass index. Primary outcomes included temporal parameters, joint rotations and moments, and ground reaction forces assessed via 3D motion capture during walking and ascending/descending stairs. Secondary outcomes included timed functional activities (sit to stand; tying shoelaces), 48 hrs lower limb activity monitoring, and patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, European Quality of Life–5 Dimensions). Results: Eight matched pairs were analyzed. Compared with controls, OA participants exhibited significant reductions in peak frontal hip and sagittal knee moments, and decreased peak anterior ground reaction force with the affected limb while walking. Ascending stairs, OA participants had slower speed, fewer strides per minute, longer cycle and stance times, and increased trunk range of motion (ROM) in assessments of both limbs; longer swing time and reduced ankle ROM in the affected limb; and increased knee frontal ROM in the unaffected limb. Descending stairs, OA participants had fewer strides per minute and decreased trunk transverse ROM in assessments of both limbs; increased knee frontal ROM in the affected limb; and longer strides, shorter stance and cycle times, increased trunk sagittal and decreased knee transverse ROMs in the unaffected limbs vs controls. Compared with controls, OA participants had slower walking cadence (120–130 vs 100–110 steps/min, respectively), took significantly longer on timed functional measures, and had significantly worse scores in patient-reported outcomes. Conclusion: Several objectives and patient-reported measures examined in this study could potentially be considered as outcomes in pharmacologic or physical therapy OA trials. Keywords: osteoarthritis, knee, 3D motion analysis, biomechanics, kinetics, gai

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68

Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man

The North Atlantic Waveguide and Downstream Impact Experiment

The North Atlantic Waveguide and Downstream Impact Experiment (NAWDEX) explored the impact of diabatic processes on disturbances of the jet stream and their influence on downstream high-impact weather through the deployment of four research aircraft, each with a sophisticated set of remote sensing and in situ instruments, and coordinated with a suite of ground-based measurements. A total of 49 research flights were performed, including, for the first time, coordinated flights of the four aircraft: the German High Altitude and Long Range Research Aircraft (HALO), the Deutsches Zentrum für Luft- und Raumfahrt (DLR) Dassault Falcon 20, the French Service des Avions Français Instrumentés pour la Recherche en Environnement (SAFIRE) Falcon 20, and the British Facility for Airborne Atmospheric Measurements (FAAM) BAe 146. The observation period from 17 September to 22 October 2016 with frequently occurring extratropical and tropical cyclones was ideal for investigating midlatitude weather over the North Atlantic. NAWDEX featured three sequences of upstream triggers of waveguide disturbances, as well as their dynamic interaction with the jet stream, subsequent development, and eventual downstream weather impact on Europe. Examples are presented to highlight the wealth of phenomena that were sampled, the comprehensive coverage, and the multifaceted nature of the measurements. This unique dataset forms the basis for future case studies and detailed evaluations of weather and climate predictions to improve our understanding of diabatic influences on Rossby waves and the downstream impacts of weather systems affecting Europe