Pilot Study of Delayed ICOS/ICOS-L Blockade With alphaCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results: Median allograft survival was similar between ICOS-Ig + alphaCD40 (120 days, 120-125 days) and alphaCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4(+) TEM cells were decreased in peripheral blood (115 +/- 24) and mLNs (49 +/- 1.9%) during ICOS-Ig treatment compared with monotherapy (214 +/- 27%, P = 0.01; 72 +/- 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions: Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model

Mancha3D code: Multi-purpose Advanced Non-ideal MHD Code for High resolution simulations in Astrophysics

The Mancha3D code is a versatile tool for numerical simulations of magnetohydrodynamic processes in solar/stellar atmospheres. The code includes non-ideal physics derived from plasma partial ionization, a realistic equation of state and radiative transfer, which allows performing high quality realistic simulations of magneto-convection, as well as idealized simulations of particular processes, such as wave propagation, instabilities or energetic events. The paper summarizes the equations and methods used in the Mancha3D code. It also describes its numerical stability and parallel performance and efficiency. The code is based on a finite difference discretization and memory-saving Runge-Kutta (RK) scheme. It handles non-ideal effects through super-time stepping and Hall diffusion schemes, and takes into account thermal conduction by solving an additional hyperbolic equation for the heat flux. The code is easily configurable to perform different kinds of simulations. Several examples of the code usage are given. It is demonstrated that splitting variables into equilibrium and perturbation parts is essential for simulations of wave propagation in a static background. A perfectly matched layer (PML) boundary condition built into the code greatly facilitates a non-reflective open boundary implementation. Spatial filtering is an important numerical remedy to eliminate grid-size perturbations enhancing the code stability. Parallel performance analysis reveals that the code is strongly memory bound, which is a natural consequence of the numerical techniques used, such as split variables and PML boundary conditions. Both strong and weak scalings show adequate performance up till several thousands of CPUs

Angiotensin II Activates the Calcineurin/NFAT Signaling Pathway and Induces Cyclooxygenase-2 Expression in Rat Endometrial Stromal Cells

Cyclooxygenase (COX)-2, the inducible isoform of cyclooxygenase, plays a role in the process of uterine decidualization and blastocyst attachment. On the other hand, overexpression of COX-2 is involved in the proliferation of the endometrial tissue during endometriosis. Deregulation of the renin-angiotensin-system plays a role in the pathophysiology of endometriosis and pre-eclampsia. Angiotensin II increases intracellular Ca2+ concentration by targeting phospholypase C-gamma in endometrial stromal cells (ESC). A key element of the cellular response to Ca2+ signals is the activity of the Ca2+- and calmodulin-dependent phosphatase calcineurin. Our first aim was to study whether angiotensin II stimulated Cox-2 gene expression in rat ESC and to analyze whether calcineurin activity was involved. In cells isolated from non-pregnant uteri, COX-2 expression -both mRNA and protein- was induced by co-stimulation with phorbol ester and calcium ionophore (PIo), as well as by angiotensin II. Pretreatment with the calcineurin inhibitor cyclosporin A inhibited this induction. We further analyzed the role of the calcineurin/NFAT signaling pathway in the induction of Cox-2 gene expression in non-pregnant rat ESC. Cyclosporin A abolished NFATc1 dephosphorylation and translocation to the nucleus. Cyclosporin A also inhibited the transcriptional activity driven by the Cox-2 promoter. Exogenous expression of the peptide VIVIT -specific inhibitor of calcineurin/NFAT binding- blocked the activation of Cox-2 promoter and the up-regulation of COX-2 protein in these cells. Finally we analyzed Cox-2 gene expression in ESC of early-pregnant rats. COX-2 expression -both mRNA and protein- was induced by stimulation with PIo as well as by angiotensin II. This induction appears to be calcineurin independent, since it was not abrogated by cyclosporin A. In conclusion, angiotensin II induced Cox-2 gene expression by activating the calcineurin/NFAT signaling pathway in endometrial stromal cells of non-pregnant but not of early-pregnant rats. These results might be related to differential roles that COX-2 plays in the endometrium

Comprehensive evolved gas analysis of amorphous precursors for S-doped titania by in situ TG-FTIR and TG/DTA-MS. Part 1

Decomposition of an amorphous precursor for S-doped titania (TiO2) nanopowders, prepared by controlled sol-gel hydrolysis-condensation of titanium(IV) tetraisopropoxide and thiourea in aqueous isopropanol, has been studied up to 800 degrees C in flowing air by simultaneous thermogravimetric and differential thermal analysis coupled online with quadrupole mass spectrometer (TG/DTA-MS) and FTIR spectrometric gas cell (TG-FTIR) for analysis of gases and their evolution dynamics (by evolved gas analysis, EGA) in order to explore and model thermal annealing processes of fabrication techniques leading to S:TiO2 photocatalysts with photocatalytic activities under visible light. Precursor sample prepared with thiourea, releases first water endothermically from room temperature to 190 degrees C, carbonyl sulfide (COS) from 120 to 280 degrees C in two stages, and ammonia (NH3) from 170 to 450 degrees C in three steps. Evolution of CO2, sulfur dioxide (SO2), and dinitrogen oxide, as of oxidation products, (N2O), as of oxidation products, occurs between 150 and 220,180 and 330, 280 and 450 degrees C, respectively. Exothermic DTA peaks at 170, 220, and 310 degrees C correspond to the maximum rate of CO2, SO2, and N2O evolution, respectively. The fourth exothermic heat effect at 430 degrees C is probably due to the simultaneous burning out of residual carbonaceous-species, solid-state oxidation of residual sulfureous and/or sulfurous species, and transformation of amorphous titania into anatase. Titanium-oxo-sulfate formation at 500 degrees C has been confirmed by FTIR. Furthermore, evolution of sulfur dioxide reoccurs again in a definite step between 550 and 800 degrees C, indicating the significant extent of previous sulfate formation processes. Anatase, which formed also in the exothermic peak at 430 degrees C, keeps its structure, no rutile formation is detected below or at 800 degrees C by XRD. (C) 2008 Elsevier B.V. All rights reserved

Properties of the Pb(Mg1/3Nb2/3)O3 Ceramics Prepared by Using Two Different Mg Precursors

Pb(Mg1/3Nb2/3)O3 ceramics prepared via columbite method by using two types of Mg precursors, i.e. MgO and (MgCO3)4\ub7Mg(OH)2\ub74H2O exhibit high crystallinity and high densification after sintering at 1200\ub0C. Higher amounts of pyrochlore phases were detected in the PMN sample obtained by using (MgCO3)4\ub7 Mg(OH)2.4H2O as precursor. This compositional difference, determines, for all frequencies, a shift of 3c 50 K of the temperature corresponding to the permittivity maximum Tm for the sample derived from (MgCO3)4\ub7Mg(OH)2\ub74H2O. From this reason, better dielectric properties were obtained at room temperature for this PMN sample, although a higher dielectric permittivity at Tm was obtained for the sample derived from MgO precursor