Recipient‐derived EDA fibronectin promotes cardiac allograft fibrosis

Advances in donor matching and immunosuppressive therapies have decreased the prevalence of acute rejection of cardiac grafts; however, chronic rejection remains a significant obstacle for long‐term allograft survival. While initiating elements of anti‐allograft immune responses have been identified, the linkage between these factors and the ultimate development of cardiac fibrosis is not well understood. Tissue fibrosis resembles an exaggerated wound healing response, in which extracellular matrix (ECM) molecules are central. One such ECM molecule is an alternatively spliced isoform of the ubiquitous glycoprotein fibronectin (FN), termed extra domain A‐containing cellular fibronectin (EDA cFN). EDA cFN is instrumental in fibrogenesis; thus, we hypothesized that it might also regulate fibrotic remodelling associated with chronic rejection. We compared the development of acute and chronic cardiac allograft rejection in EDA cFN‐deficient (EDA −/− ) and wild‐type (WT) mice. While EDA −/− mice developed acute cardiac rejection in a manner indistinguishable from WT controls, cardiac allografts in EDA −/− mice were protected from fibrosis associated with chronic rejection. Decreased fibrosis was not associated with differences in cardiomyocyte hypertrophy or intra‐graft expression of pro‐fibrotic mediators. Further, we examined expression of EDA cFN and total FN by whole splenocytes under conditions promoting various T‐helper lineages. Conditions supporting regulatory T‐cell (Treg) development were characterized by greatest production of total FN and EDA cFN, though EDA cFN to total FN ratios were highest in Th1 cultures. These findings indicate that recipient‐derived EDA cFN is dispensable for acute allograft rejection responses but that it promotes the development of fibrosis associated with chronic rejection. Further, conditions favouring the development of regulatory T cells, widely considered graft‐protective, may drive production of ECM molecules which enhance deleterious remodelling responses. Thus, EDA cFN may be a therapeutic target for ameliorating fibrosis associated with chronic cardiac allograft rejection. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90405/1/3010_ftp.pd

The ALICE Zero Degree Calorimeters

In the ALICE experiment at Cern LHC, a set of hadron calorimeters will be used to determine the centrality of the Pb-Pb collision. The spectator protons and neutrons, will be separated from the ion beams, using the separator magnet (D1) of the LHC beam optics and respectively detected by a proton (ZP) and a neutron (ZN) "Zero-degree Calorimeter" (ZDC). The detectors will be placed in front of the separator D2 magnet, 115 meters away from the beam intersection point. The ZDCs are quartz-fiber spaghetti calorimeters that exploit the Cherenkov light produced by the shower particles in silica optical fibers.This technique offers the advantages of high radiation hardness (up to several Grad), fast response and reduced lateral dimension of the detectable shower. In addition, quartz-fiber calorimeters are intrinsically insensitive to radio-activation background, which produces particles below the Cherenkov threshold.The ALICE ZDC should have an energy resolution comparable with the intrinsic energy fluctuations, which range from about 20 0.000000or central events to about 5 0.000000or peripheral ones, according to simulations that use HIJING as event generator. The fiber-to-absorber filling ratio must be chosen as a good compromise between the required energy resolution and the fiber cost.The design of the proposed calorimeter will be discussed, together with the expected performances. Whenever possible, the simulated results will be compared with the experimental ones, obtained with the built prototypes and with the NA50 ZDC, which can be considered as a working prototype for the ALICE neutron calorimeter

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

J/psi azimuthal anisotropy relative to the reaction plane in Pb-Pb collisions at 158 GeV per nucleon

The J/$\psi$ azimuthal distribution relative to the reaction plane has been measured by the NA50 experiment in Pb-Pb collisions at 158 GeV/nucleon. Various physical mechanisms related to charmonium dissociation in the medium created in the heavy ion collision are expected to introduce an anisotropy in the azimuthal distribution of the observed J/$\psi$ mesons at SPS energies. Hence, the measurement of J/$\psi$ elliptic anisotropy, quantified by the Fourier coefficient v$_2$ of the J/$\psi$ azimuthal distribution relative to the reaction plane, is an important tool to constrain theoretical models aimed at explaining the anomalous J/$\psi$ suppression observed in Pb-Pb collisions. We present the measured J/$\psi$ yields in different bins of azimuthal angle relative to the reaction plane, as well as the resulting values of the Fourier coefficient v$_{2}$ as a function of the collision centrality and of the J/$\psi$ transverse momentum. The reaction plane has been estimated from the azimuthal distribution of the neutral transverse energy detected in an electromagnetic calorimeter. The analysis has been performed on a data sample of about 100 000 events, distributed in five centrality or p$_{\rm T}$ sub-samples. The extracted v$_{2}$ values are significantly larger than zero for non-central collisions and are seen to increase with p$_{\rm T}$.Comment: proceedings of HP08 conference corrected a typo in one equatio

A new measurement of J/psi suppression in Pb-Pb collisions at 158 GeV per nucleon

We present a new measurement of J/psi production in Pb-Pb collisions at 158 GeV/nucleon, from the data sample collected in year 2000 by the NA50 Collaboration, under improved experimental conditions with respect to previous years. With the target system placed in vacuum, the setup was better adapted to study, in particular, the most peripheral nuclear collisions with unprecedented accuracy. The analysis of this data sample shows that the (J/psi)/Drell-Yan cross-sections ratio measured in the most peripheral Pb-Pb interactions is in good agreement with the nuclear absorption pattern extrapolated from the studies of proton-nucleus collisions. Furthermore, this new measurement confirms our previous observation that the (J/psi)/Drell-Yan cross-sections ratio departs from the normal nuclear absorption pattern for semi-central Pb-Pb collisions and that this ratio persistently decreases up to the most central collisions.Comment: 19 pages, 10 figures. Submitted to Eur. Phys. J.

Munc18b is an essential gene in mice whose expression is limiting for secretion by airway epithelial and mast cells

Airway mucin secretion and MC (mast cell) degranulation must be tightly controlled for homoeostasis of the lungs and immune system respectively. We found the exocytic protein Munc18b to be highly expressed in mouse airway epithelial cells and MCs, and localized to the apical pole of airway secretory cells. To address its functions, we created a mouse with a severely hypomorphic Munc18b allele such that protein expression in heterozygotes was reduced by∼50%. Homozygous mutant mice were not viable, but heterozygotes showed a ∼50% reduction in stimulated release of mucin from epithelial cells and granule contents from MCs. The defect in MCs affected only regulated secretion and not constitutive or transporter-mediated secretion. The severity of passive cutaneous anaphylaxiswas also reduced by ∼50%, showing that reduction of Munc18b expression results in an attenuation of physiological responses dependent on MC degranulation. The Munc18b promoter is controlled by INR (initiator), Sp1 (specificity protein 1), Ets, CRE (cAMP-response element), GRE (glucocorticoid-response element), GATA and E-box elements in airway epithelial cells; however, protein levels did not change during mucous metaplasia induced by allergic inflammation. Taken together, the results of the present study identifyMunc18b as an essential gene that is a limiting component of the exocytic machinery of epithelial cells and MCs

Quartz fiber calorimetry

The fundamentals of a new electromagnetic and hadronic sampling calorimetry based on the detection of Cherenkov light generated in quartz optical fibers are presented. Optical fibers transport light only in a selected angular range which results in a non-obvious and absolutely unique characteristic for this new technique: showers of very narrow visible energy. In addition, the technique is characterized by radiation resistance measured in Gigarads and nanosecond signal duration. Combined, these properties make quartz fiber calorimetry a very promising technique for high intensity heavy ion experiments and for the high pseudorapidity regions of high intensity collider experiments. The results of beam tests and simulations are used to illustrate the basic properties and peculiar characteristics of this recent development

Correlazione fra stato di salute e concentrazione di vitamina D in un gruppo di soggetti anziani ricoverati in un reparto di Geriatria

La vitamina D è da sempre conosciuta come la vitamina che regola il metabolismo osseo, tuttavia studi recenti hanno evidenziato come possa essere piuttosto considerata un ormone con azione pleiotropica su molti organi e tessuti, il cui deficit può essere fattore di rischio per molte malattie come: l’osteoporosi, le fratture, le cadute, le neoplasie, le malattie cardiovascolari, le malattie autoimmuni, le malattie infettive, la BPCO e i deficit cognitivi. La vitamina D potrebbe infatti intervenire sulla patogenesi di queste condizioni croniche attraverso i suoi recettori che sono distribuiti su quasi tutti i tessuti del corpo e quindi la sua azione non si limiterebbe ad effetti calciotropici ma anche non calciotropici per via autocrina e paracrina. Lo scopo della presente tesi è stato quello di valutare l’entità del deficit di vitamina D all’interno di un gruppo di pazienti ricoverati in un reparto di geriatria e ricercare eventuali associazioni tra il deficit di tale vitamina e il loro stato di salute. Il campione esaminato mostra che i soggetti anziani deficitari di vitamina D sono soggetti affetti da più patologie croniche in particolar modo di natura cardiovascolare, con un peggior equilibrio e quindi a maggior rischio di caduta e con una peggior salute somatica valutata tramite la scala di comorbilità CIRS. È quindi molto importante prestare attenzione alla prevenzione del deficit di vitamina D, in particolar modo negli anziani, tenendo conto del favorevole rapporto costi/benefici e del tranquillizzante profilo di sicurezza

The Immunobiology of Inductive Anti-CD40L Therapy in Transplantation: Allograft Acceptance is Not Dependent Upon the Deletion of Graft-Reactive T Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73082/1/j.1600-6143.2002.20406.x.pd