GP. Substrate stiffening promotes endothelial monolayer disruption through enhanced physical forces. Am J Physiol Cell Physiol 300: C146 -C154, 2011. First published September 22, 2010; doi:10.1152/ajpcell.00195.2010.-A hallmark of many, sometimes life-threatening, inflammatory diseases and disorders is vascular leakage. The extent and severity of vascular leakage is broadly mediated by the integrity of the endothelial cell (EC) monolayer, which is in turn governed by three major interactions: cell-cell and cell-substrate contacts, soluble mediators, and biomechanical forces. A potentially critical but essentially uninvestigated component mediating these interactions is the stiffness of the substrate to which the endothelial monolayer is adherent. Accordingly, we investigated the extent to which substrate stiffening influences endothelial monolayer disruption and the role of cell-cell and cell-substrate contacts, soluble mediators, and physical forces in that process. Traction force microscopy showed that forces between cell and cell and between cell and substrate were greater on stiffer substrates. On stiffer substrates, these forces were substantially enhanced by a hyperpermeability stimulus (thrombin, 1 U/ml), and gaps formed between cells. On softer substrates, by contrast, these forces were increased far less by thrombin, and gaps did not form between cells. This stiffness-dependent force enhancement was associated with increased Rho kinase activity, whereas inhibition of Rho kinase attenuated baseline forces and lessened thrombin-induced inter-EC gap formation. Our findings demonstrate a central role of physical forces in EC gap formation and highlight a novel physiological mechanism. Integrity of the endothelial monolayer is governed by its physical microenvironment, which in normal circumstances is compliant but during pathology becomes stiffer. contraction; human umbilical vein endothelial cells; permeability; traction force; cell-cell contact; cell-substrate contact; substrate stiffness; Rho kinase; vascular endothelial cadherin; thrombin THE OVERALL INTEGRITY and barrier properties of the endothelial cell (EC) monolayer are governed by three main categories of inputs: cell-cell and cell-substrate contacts, soluble mediators (e.g., thrombin, histamine, spingosphine 1-phosphate, and nitric oxide), and biomechanics (e.g., innate monolayer forces, shear forces, and stretch) (33). In vivo, these inputs are integrated by the EC monolayer to regulate its overall integrity and responses to inflammatory stimuli. Characterizing these inputs and their interrelationships is thus of central importance for understanding vascular biology and inflammation as a whole.A potentially critical, but entirely ignored, component of the EC environment that may influence the aforementioned inputs and their interactions is stiffness of the substrate to which the EC monolayer is adherent. This substrate stiffness varies greatly among diverse physiological settings (12,13,32,59), is enhanced with aging (21, 40), and is exacerbate...

We introduce a new perspective and a generalization of spectral networks for 4d N = 2 theories of class S associated to Lie algebras g = A n , D n , E 6 , and E 7 . Spectral networks directly compute the BPS spectra of 2d theories on surface defects coupled to the 4d theories. A Lie algebraic interpretation of these spectra emerges naturally from our construction, leading to a new description of 2d-4d wall-crossing phenomena. Our construction also provides an efficient framework for the study of BPS spectra of the 4d theories. In addition, we consider novel types of surface defects associated with minuscule representations of g.

We consider the low-energy limit of the two-dimensional theory on k M2-branes suspended between a straight M5-brane and a curved M5-brane. We argue that it is described by an N=(2,2) supersymmetric gauge theory with no matter fields but with a non-trivial twisted superpotential, and also by an N=(2,2) supersymmetric Landau-Ginzburg model, such that the (twisted) superpotentials are determined by the shape of the M5-branes. We find particular cases realize Kazama-Suzuki models. Evidence is provided by the study of ground states, chiral rings, BPS spectra and S^2 partition functions of the systems.Comment: 27 pages, 48 color figures; v2: several minor change

We define "BPS graphs" on punctured Riemann surfaces associated with A N −1 theories of class S. BPS graphs provide a bridge between two powerful frameworks for studying the spectrum of BPS states: spectral networks and BPS quivers. They arise from degenerate spectral networks at maximal intersections of walls of marginal stability on the Coulomb branch. While the BPS spectrum is ill-defined at such intersections, a BPS graph captures a useful basis of elementary BPS states. The topology of a BPS graph encodes a BPS quiver, even for higher-rank theories and for theories with certain partial punctures. BPS graphs lead to a geometric realization of the combinatorics of Fock-Goncharov Ntriangulations and generalize them in several ways.

Oxorhenium catalysts effectively transform biomass-derived polyols into corresponding alkenes via deoxydehydration (DODH) with a secondary alcohol as a hydrogen donor. This study describes the preparation of unsupported rhenium oxide nanoparticles (ReO x NPs), their use as DODH heterogeneous catalyst, and changes in the speciation and structure of Re during catalysis leading to a possible mechanism for DODH by a heterogeneous catalyst. The unsupported nanoparticles catalyze various polyols transformation to produce alkenes with high efficiency and recyclability. X-ray spectroscopy analysis shows that the structure of as-prepared ReO x NPs is similar to perrhenate with oxidation state between Re­(VI) and Re­(VII). Under reaction conditions and postcatalysis, the ReO x NPs are reduced by approximately two oxidation units. Kinetic isotope effect demonstrates that dissociation of a C–H bond during reduction of ReO x NPs by 3-octanol is part of the rate-determining step. Based on all experimental observations, the mechanism of DODH catalysis with unsupported ReO x NPs involving a Re­(VII)/Re­(V) redox pair is proposed.

Abstract:We study the BPS spectrum of four-dimensional N = 2 superconformal field theory of Argyres-Douglas type, obtained via twisted compactification of six-dimensional A N −1 (2, 0) theory on a sphere with an irregular puncture, by using spectral networks. We give strong evidence of the equivalence of N = 2 superconformal field theories from sixdimensional theories of different ranks by systematically comparing the chamber structure and wall-crossing phenomena.

Abstract:We study vacua and BPS spectra of canonical surface defects of class S theories in different decoupling limits using ADE spectral networks. In some regions of the IR moduli spaces of these 2d-4d systems, the mixing between 2d and 4d BPS states is suppressed, and the spectrum of 2d-4d BPS states becomes that of a 2d N = (2, 2) theory. For some decoupling limits, we identify the 2d theories describing the surface defects with nonlinear sigma models and coset models that have been previously studied. We also study certain cases where the decoupling limit of a surface defect exhibits a set of vacua and a BPS spectrum that appear to be entirely new. A detailed analysis of these spectra and their wall-crossing behavior is performed.

Ozone causes airway hyperresponsiveness (AHR) and pulmonary inflammation. Rho kinase (ROCK) is a key regulator of smooth muscle cell contraction and inflammatory cell migration. To determine the contribution of the two ROCK isoforms ROCK1 and ROCK2 to ozone-induced AHR, we exposed wild-type, ROCK1(+/-), and ROCK2(+/-) mice to air or ozone (2 ppm for 3 h) and evaluated mice 24 h later. ROCK1 or ROCK2 haploinsufficiency did not affect airway responsiveness in air-exposed mice but significantly reduced ozone-induced AHR, with a greater reduction in ROCK2(+/-) mice despite increased bronchoalveolar lavage (BAL) inflammatory cells in ROCK2(+/-) mice. Compared with wild-type mice, ozone-induced increases in BAL hyaluronan, a matrix protein implicated in ozone-induced AHR, were lower in ROCK1(+/-) but not ROCK2(+/-) mice. Ozone-induced increases in other inflammatory moieties reported to contribute to ozone-induced AHR (IL-17A, osteopontin, TNFα) were not different in wild-type vs. ROCK1(+/-) or ROCK2(+/-) mice. We also observed a dose-dependent reduction in ozone-induced AHR after treatment with the ROCK1/ROCK2 inhibitor fasudil, even though fasudil was administered after induction of inflammation. Ozone increased pulmonary expression of ROCK2 but not ROCK1 or RhoA. A ROCK2 inhibitor, SR3677, reduced contractile forces in primary human airway smooth muscle cells, confirming a role for ROCK2 in airway smooth muscle contraction. Our results demonstrate that ozone-induced AHR requires ROCK. Whereas ROCK1-dependent changes in hyaluronan may contribute to ROCK1's role in O3-induced AHR, the role of ROCK2 is downstream of inflammation, likely at the level of airway smooth muscle contraction.