Current-induced cooling phenomenon in a two-dimensional electron gas under a magnetic field

We investigate the spatial distribution of temperature induced by a dc current in a two-dimensional electron gas (2DEG) subjected to a perpendicular magnetic field. We numerically calculate the distributions of the electrostatic potential phi and the temperature T in a 2DEG enclosed in a square area surrounded by insulated-adiabatic (top and bottom) and isopotential-isothermal (left and right) boundaries (with phi_{left} < phi_{right} and T_{left} =T_{right}), using a pair of nonlinear Poisson equations (for phi and T) that fully take into account thermoelectric and thermomagnetic phenomena, including the Hall, Nernst, Ettingshausen, and Righi-Leduc effects. We find that, in the vicinity of the left-bottom corner, the temperature becomes lower than the fixed boundary temperature, contrary to the naive expectation that the temperature is raised by the prevalent Joule heating effect. The cooling is attributed to the Ettingshausen effect at the bottom adiabatic boundary, which pumps up the heat away from the bottom boundary. In order to keep the adiabatic condition, downward temperature gradient, hence the cooled area, is developed near the boundary, with the resulting thermal diffusion compensating the upward heat current due to the Ettingshausen effect.Comment: 25 pages, 7 figure

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis

Objectives: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. Materials and Methods: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. Results: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (P=0.0096) and 3.00 (P=0.0198), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (odds ratio 4.56; P=0.0076). Clinical Significance: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis

Serum anti-GM2 and anti-GalNAc-GD1a IgG antibodies are biomarkers for acute canine polyradiculoneuritis

OBJECTIVES: A previous single-country pilot study indicated serum anti-GM2 and anti-GA1 anti-glycolipid antibodies as potential biomarkers for acute canine polyradiculoneuritis. This study aims to validate these findings in a large geographically heterogenous cohort. MATERIALS AND METHODS: Sera from 175 dogs clinically diagnosed with acute canine polyradiculoneuritis, 112 dogs with other peripheral nerve, cranial nerve or neuromuscular disorders and 226 neurologically normal dogs were screened for anti-glycolipid antibodies against 11 common glycolipid targets to determine the immunoglobulin G anti-glycolipid antibodies with the highest combined sensitivity and specificity for acute canine polyradiculoneuritis. RESULTS: Anti-GM2 anti-glycolipid antibodies reached the highest combined sensitivity and specificity (sensitivity: 65.1%, 95% confidence interval 57.6 to 72.2%; specificity: 90.2%, 95% confidence interval 83.1 to 95.0%), followed by anti-GalNAc-GD1a anti-glycolipid antibodies (sensitivity: 61.7%, 95% confidence interval 54.1 to 68.9%; specificity: 89.3%, 95% confidence interval 82.0 to 94.3%) and these anti-glycolipid antibodies were frequently present concomitantly. Anti-GA1 anti-glycolipid antibodies were detected in both acute canine polyradiculoneuritis and control animals. Both for anti-GM2 and anti-GalNAc-GD1a anti-glycolipid antibodies, sex was found a significantly associated factor with a female to male odds ratio of 2.55 (1.27 to 5.31) and 3.00 (1.22 to 7.89), respectively. Anti-GalNAc-GD1a anti-glycolipid antibodies were more commonly observed in dogs unable to walk (OR 4.56, 1.56 to 14.87). CLINICAL SIGNIFICANCE: Anti-GM2 and anti-GalNAc-GD1a immunoglobulin G anti-glycolipid antibodies represent serum biomarkers for acute canine polyradiculoneuritis.This study was funded by PetSavers, the charitable division of the BSAVA, and by The Wellcome Trust (Grants 092805 and 202789 awarded to HJW).https://onlinelibrary.wiley.com/journal/17485827Companion Animal Clinical Studie

The bradykinin/B1 receptor promotes angiogenesis by upregulation of endogenous FGF-2 in endothelium via the nitric oxide synthase pathway.

Bradykinin (BK) mediates inflammation and contributes to angiogenesis. We assessed the mechanisms for BK contribution to angiogenesis. Nanomolar concentrations of BK induced angiogenesis in rabbit corneas in absence of inflammation. The effect was dose-dependent and mediated by the B1 receptor. B2 receptor stimulation failed to directly promote vascular growth unless inflammation was induced. Anti-fibroblast growth factor-2 (FGF-2) antibody blocked the effect of BK or B1 receptor agonist. In postcapillary venular endothelial cells (CVEC), B2 receptor activation induced inositol phosphate turnover and calcium transients, whereas the B1 receptor was coupled to nitric oxide synthase (NOS) up-regulation and activation and cGMP increase. Differential RT-PCR and Western blot analysis revealed FGF- 2 up-regulation in cells exposed to BK or to the selective B1 agonist, whereas the B2 agonist was without effect. Consistently, BK and the B1 but not the B2 agonist exerted a proliferative effect on CVEC, which was prevented by anti-FGF-2 antibody and by NOS inhibition. These results demonstrate that BK is angiogenic despite its proinflammatory activity and that the B1 receptor is involved. The B1 receptor is coupled to NOS activation and FGF-2 up-regulation, events not shared by the B2 receptor activation

Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF.

We reported previously that NO is responsible for the angiogenesis produced by endothelium-dependent vasodilating peptides. To investigate the mechanisms by which NO controls angiogenesis, NO was assessed for the ability to affect cell proliferation and upregulation of urokinase-type plasminogen activator (uPA) induced by basic fibroblast growth factor (bFGF) when added exogenously to or when produced endogenously by coronary venular endothelial cells (CVECs). The treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA upregulation and cell proliferation, which were prevented by anti-bFGF antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase–polymerase chain reaction of bFGF mRNA. SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N -monomethyl-L-arginine. We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP. This signaling paradigm may provide an important link between shear rate, NO, bFGF, and coronary angiogenesis

Nitric oxide is an upstream signal of vascular endothelial growth factor-induced extracellular signal-regulated kinase 1/2 activation in postcapillary endothelium

We recently demonstrated that nitric oxide (NO) significantly contributes to the mitogenic effect of vascular endothelial growth factor (VEGF), suggesting a role for the NO pathway in the signaling cascade following kinase-derivative receptor activation in vascular endothelium. The aim of this study was to investigate the intracellular pathways linked to VEGF/NO-induced endothelial cell proliferation. We assessed the activity of the mitogen-activated protein kinase (MAPK) that is specifically activated by growth factors, extracellular-regulated kinase (ERK1/2), on cultured microvascular endothelium isolated from coronary postcapillary venules. ERK1/2 was immunoprecipitated, and its activity was assessed with an immunocomplex kinase assay. In endothelial cells exposed for 5 min to the NO donor drug sodium nitroprusside at a concentration of 100 microM, ERK1/2 activity significantly increased. VEGF produced a time- and concentration-dependent activation of ERK1/2. Maximal activity was obtained after 5 min of stimulation at a concentration of 10 ng/ml. The specific MAPK kinase inhibitor PD 98059 abolished ERK1/2 activation and endothelial cell proliferation in a concentration-dependent manner in response to VEGF and sodium nitroprusside. The NO synthase inhibitor Nomega-monomethyl-L-arginine, as well as the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, blocked the activation of ERK1/2 induced by VEGF, suggesting that NO and cGMP contributed to the VEGF-dependent ERK1/2 activation. These results demonstrate for the first time that kinase-derivative receptor activation triggers the NO synthase/guanylate cyclase pathway to activate the MAPK cascade and substantiates the hypothesis that the activation of ERK1/2 is necessary for VEGF-induced endothelial cell proliferatio

The heparin binding 25kDa fragment of thrombospondin-1 promotes angiogenesis and modulates gelatinases and TIMP-2 in endothelial cells

The hypothesis that thrombospondin-1 (TSP-1) can exert opposite effects on angiogenesis depending on the functional status of its domains/fragments was investigated. In the rabbit cornea, TSP-1 inhibited angiogenesis induced by fibroblast growth factor-2 (FGF-2). However, when tested per se, TSP-1 was able to elicit an angiogenic response comparable to that induced by FGF-2. Induction of angiogenesis was dose-dependent (20 ng - 2 μg/pellet), was prevented by anti-TSP antibodies or by heat-inactivation of TSP-1, and was not due to inflammatory mediators, to FGF-2 or to TGF-β. Equimolar concentrations of the 25 kDa heparin binding fragment of TSP-1 were even more efficient than the whole molecule, and promoted the angiogenic activity of FGF-2. On the contrary, the 140 kDa fragment of TSP-1 did not induce angiogenesis and turned off the angiogenic response to FGF-2. The 25 kDa fragment and TSP-1, but not the 140 kDa fragment, increased endothelial cell invasiveness and stimulated the production and activation of matrix metalloproteinase-2 (MMP-2). Moreover, the 25 kDa fragment reduced the synthesis of the MMP-2 inhibitor TIMP-2, while the 140 kDa fragment caused a twofold increase in TIMP-2 production and inhibited MMPs stimulation by TSP-1 and FGF-2. We conclude that TSP-1 is a source of smaller mediators of angiogenesis, which affect in an opposite way endothelial cell functions and proteolytic activity, thus resulting in an opposite final effect on angiogenesis