Roe Solver with Entropy Corrector for Uncertain Hyperbolic Systems

International audienceThis paper deals with intrusive Galerkin projection methods with Roe-type solver for uncertain hyperbolic systems using a finite volume discretization in physical space and a piecewise continuous representation at the stochastic level. The aim of this paper is to design a cost-effective adaptation of the deterministic Dubois and Mehlman corrector to avoid entropy-violating shocks in the presence of sonic points. The adaptation relies on an estimate of the eigenvalues and eigenvectors of the Galerkin Jacobian matrix of the deterministic system of the stochastic modes of the solution and on a correspondence between these approximate eigenvalues and eigenvectors for the intermediate states considered at the interface. Some indicators are derived to decide where a correction is needed, thereby reducing considerably the computational costs. The effectiveness of the proposed corrector is assessed on the Burgers and Euler equations including sonic points

Smooth Muscle Cell Phenotype Modulation and Contraction on Native and Cross-Linked Polyelectrolyte Multilayers

Smooth muscle cells convert between a motile, proliferative “synthetic ” phenotype and a sessile, “contractile ” phenotype. The ability to manipulate the phenotype of aortic smooth muscle cells with thin biocompatible polyelectrolyte multilayers (PEMUs) with common surface chemical characteristics but varying stiffness was investigated. The stiffness of (PAH/ PAA) PEMUs was varied by heating to form covalent amide bond cross-links between the layers. Atomic force microscopy (AFM) showed that cross-linked PEMUs were thinner than those that were not cross-linked. AFM nanoindentation demonstrated that the Young’s modulus ranged from 6 MPa for hydrated native PEMUs to more than 8 GPa for maximally cross-linked PEMUs. Rat aortic A7r5 smooth muscle cells cultured on native PEMUs exhibited morphology and motility of synthetic cells and expression of the synthetic phenotype markers vimentin, tropomyosin 4, and nonmuscle myosin heavy chain IIB (nmMHCIIB). In comparison, cells cultured on maximally cross-linked PEMUs exhibited the phenotype markers calponin, smooth muscle myosin heavy chain (smMHC), myocardin, transgelin, and smooth muscle R-actin (smActin) that are characteristic of the smooth muscle “contractile ” phenotype. Consistent with those cells being “contractile”, A7r5 cells grown on cross-linked PEMUs produced contractile force when stimulated with a Ca2+ ionophore

In Vivo Delta Opioid Receptor Internalization Controls Behavioral Effects of Agonists

GPCRs regulate a remarkable diversity of biological functions, and are thus often targeted for drug therapies. Stimulation of a GPCR by an extracellular ligand triggers receptor signaling via G proteins, and this process is highly regulated. Receptor activation is typically accompanied by desensitization of receptor signaling, a complex feedback regulatory process of which receptor internalization is postulated as a key event. The in vivo significance of GPCR internalization is poorly understood. In fact, the majority of studies have been performed in transfected cell systems, which do not adequately model physiological environments and the complexity of integrated responses observed in the whole animal.In this study, we used knock-in mice expressing functional fluorescent delta opioid receptors (DOR-eGFP) in place of the native receptor to correlate receptor localization in neurons with behavioral responses. We analyzed the pain-relieving effects of two delta receptor agonists with similar signaling potencies and efficacies, but distinct internalizing properties. An initial treatment with the high (SNC80) or low (AR-M100390) internalizing agonist equally reduced CFA-induced inflammatory pain. However, subsequent drug treatment produced highly distinct responses. Animals initially treated with SNC80 showed no analgesic response to a second dose of either delta receptor agonist. Concomitant receptor internalization and G-protein uncoupling were observed throughout the nervous system. This loss of function was temporary, since full DOR-eGFP receptor responses were restored 24 hours after SNC80 administration. In contrast, treatment with AR-M100390 resulted in retained analgesic response to a subsequent agonist injection, and ex vivo analysis showed that DOR-eGFP receptor remained G protein-coupled on the cell surface. Finally SNC80 but not AR-M100390 produced DOR-eGFP phosphorylation, suggesting that the two agonists produce distinct active receptor conformations in vivo which likely lead to differential receptor trafficking.Together our data show that delta agonists retain full analgesic efficacy when receptors remain on the cell surface. In contrast, delta agonist-induced analgesia is abolished following receptor internalization, and complete behavioral desensitization is observed. Overall these results establish that, in the context of pain control, receptor localization fully controls receptor function in vivo. This finding has both fundamental and therapeutic implications for slow-recycling GPCRs

Intrusive Projection Methods with Upwinding for Uncertain Nonlinear Hyperbolic Systems ✩

This paper deals with stochastic spectral methods for uncertainty propagation and quantification in nonlinear hyperbolic systems of conservation laws. We consider problems with parametric uncertainty in initial conditions and model coefficients, whose solutions exhibit discontinuities in physical as well as in stochastic spaces. The stochastic spectral method relies on multi-resolution schemes where the stochastic space is discretized using tensor-product stochastic elements supporting local polynomial bases. A Galerkin projection is used to derive a system of deterministic equations for the stochastic modes of the solution. Hyperbolicity of the resulting Galerkin system is analyzed. A finite volume scheme with a Roe-type solver is used for discretization in physical space and time. An original technique is introduced for the fast evaluation of approximate upwind matrices, which is particularly well adapted to local polynomial bases. Efficiency and robustness of the overall method are assessed on the Burgers and Euler equations with shocks

Ephrin B1 maintains apical adhesion of neural progenitors.

Apical neural progenitors are polarized cells for which the apical membrane is the site of cell-cell and cell-extracellular matrix adhesion events that are essential for maintaining the integrity of the developing neuroepithelium. Apical adhesion is important for several aspects of the nervous system development, including morphogenesis and neurogenesis, yet the mechanisms underlying its regulation remain poorly understood. Here, we show that ephrin B1, a cell surface protein that engages in cell signaling upon binding cognate Eph receptors, controls normal morphogenesis of the developing cortex. Efnb1-deficient embryos exhibit morphological alterations of the neuroepithelium that correlate with neural tube closure defects. Using loss-of-function experiments by ex vivo electroporation, we demonstrate that ephrin B1 is required in apical progenitors (APs) to maintain their apical adhesion. Mechanistically, we show that ephrin B1 controls cell-ECM adhesion by promoting apical localization of integrin β1 and we identify ADP-ribosylation factor 6 (Arf6) as an important effector of ephrin B1 reverse signaling in apical adhesion of APs. Our results provide evidence for an important role for ephrin B1 in maintaining the structural integrity of the developing cortex and highlight the importance of tightly controlling apical cell-ECM adhesion for neuroepithelial development.journal articleresearch support, non-u.s. gov't2013 May2013 04 11importe