Selective Expression of the Vβ14 T Cell Receptor on Leishmania guyanensis-Specific CD8+ T Cells during Human Infection

Peripheral blood mononuclear cells from subjects never exposed to Leishmania were stimulated with Leishmania guyanensis. We demonstrated that L. guyanensis-stimulated CD8+ T cells produced interferon (IFN)-γ and preferentially expressed the Vb14 T cell receptor (TCR) gene family. In addition, these cells expressed cutaneous lymphocyte antigen and CCR4 surface molecules, suggesting that they could migrate to the skin. Results obtained from the lesions of patients with localized cutaneous leishmaniaisis (LCL) showed that Vβ14 TCR expression was increased in most lesions (63.5%) and that expression of only a small number of Vb gene families (Vβ1, Vβ6, Vβ9, Vβ14, and Vβ24) was increased. The presence of Vβ14 T cells in tissue confirmed the migration of these cells to the lesion site. Thus, we propose the following sequence of events during infection with L. guyanensis. After initial exposure to L. guyanensis, CD8+ T cells preferentially expressing the Vb14 TCR and secreting IFN-γ develop and circulate in the periphery. During the infection, these cells migrate to the skin at the site of the parasitic infection. The role of these Vβ14 CD8+ T cells in resistance to infection remains to be determined conclusivel

In Leishmaniasis due to Leishmania guyanensis infection, distinct intralesional interleukin-10 and foxp3 mRNA expression are associated with unresponsiveness to treatment

The presence of intralesional natural regulatory T cells, characterized by the expression of Foxp3 mRNA, was analyzed in patients with localized leishmaniasis due to Leishmania guyanensis infection that was unresponsive to treatment with pentamidine isethionate. Foxp3 mRNA levels were associated with unresponsiveness to treatment among patients with a lesion duration of ⩾1 month, but this association was not observed among patients with a lesion duration of <1 month. In conclusion, high intralesional expression of Foxp3 might be an indicator of poor response to treatment, depending on the duration of lesion

The bZIP Transcription Factor Rca1p Is a Central Regulator of a Novel CO2 Sensing Pathway in Yeast

Like many organisms the fungal pathogen Candida albicans senses changes in the environmental CO2 concentration. This response involves two major proteins: adenylyl cyclase and carbonic anhydrase (CA). Here, we demonstrate that CA expression is tightly controlled by the availability of CO2 and identify the bZIP transcription factor Rca1p as the first CO2 regulator of CA expression in yeast. We show that Rca1p upregulates CA expression during contact with mammalian phagocytes and demonstrate that serine 124 is critical for Rca1p signaling, which occurs independently of adenylyl cyclase. ChIP-chip analysis and the identification of Rca1p orthologs in the model yeast Saccharomyces cerevisiae (Cst6p) point to the broad significance of this novel pathway in fungi. By using advanced microscopy we visualize for the first time the impact of CO2 build-up on gene expression in entire fungal populations with an exceptional level of detail. Our results present the bZIP protein Rca1p as the first fungal regulator of carbonic anhydrase, and reveal the existence of an adenylyl cyclase independent CO2 sensing pathway in yeast. Rca1p appears to regulate cellular metabolism in response to CO2 availability in environments as diverse as the phagosome, yeast communities or liquid culture

Experimental and Numerical Study of the Thermal Performance of a Film Cooled Turbine Platform

Detailed surface measurements of the thermal performance of a film cooling system have been performed on the endwall of a nozzle guide vane (NGV) mounted in a linear cascade facility at EPFL. An external cooling scheme including several rows of fan-shaped and cylindrical cooling holes has been designed. By testing different cooling flow rates at a NGV exit Reynolds number of 1.7E+06 and Mach number of 0.88, detailed aerodynamic and heat transfer values were obtained destined to assess the design tools for film cooled platforms. The surface static pressure distribution and the film cooling effectiveness on the endwall surface have been experimentally determined. The measurements were obtained applying the pressure sensitive paint technique measuring the coolant gas concentration. An engine representative density ratio between the coolant and the external hot gas flow was achieved by the injection of CO2. The working conditions of the test case similar to realistic engine conditions allow for the validation of in-house CFD codes and the investigation of the reliability of modern commercial tools in such a complex cooling system. The numerical campaign has been performed on the same numerical grid, using the commercial codes FLUENT and CFX, used by EPFL and MTU respectively. A detailed analysis of the grid effects on the obtained results has been previously realised as well as the study of the influence of the modelling approximations. Three cooling mass flows have been simulated and the performance parameters of the film cooling system have been compared to the experimentally obtained data. Special emphasis has been put on the jet penetration effects and on the interaction of secondary flows with the coolant flow. The experimental and numerical efforts were part of the EU funded research project TATEF2 (Turbine Aero-Thermal External Flows 2)

Comparison of Numerical Investigations With Measured Heat Transfer Performance of a Film Cooled Turbine Vane

Detailed surface measurements of the heat transfer coefficient and the film cooling effectiveness by application of the transient liquid crystal method were carried out on a heavily film cooled nozzle guide vane (NGV) in a linear cascade wind tunnel at the EPFL as part of the European Research Project TATEF2 (Turbine Aero-Thermal External Flows 2). The external cooling setup included a showerhead cooling scheme and suction and pressure side of the airfoil several rows of fanshaped cooling holes. By testing two different cooling flow rates at a NGV exit Reynolds number of 1.46E+06, detailed aerodynamic and heat transfer measurement data were obtained that can be used for validation of numerical codes and design tools for cooled airfoils. The data include the NGV surface static pressure distribution and wall heat transfer and film cooling effectiveness obtained by application of the transient liquid crystal technique. An engine representative density ratio between the coolant and the external hot gas flow was achieved by using CO2 as coolant gas. For the coupled simulation of internal cooling and external flow the numerical model was composed of the cooling air feeding the internal plenum, the cooling holes, and the outer external flow domain. An unstructured mesh was generated for the simulations by applying two different commercial CFD codes (Fluent and CFX). Identical boundary conditions were chosen in order to allow for a direct comparison of both codes. The computations were carried in two ways, first using a builtin transition model and second by imposing fully turbulent flow starting at the leading edge. For both codes the same built-in turbulence models were applied. The computations were set up to solve for the aerodynamic flow quantities both within and around the test model and for the thermal quantities on the vane surface, i.e. heat transfer coefficient and film cooling effectiveness. The computational results from the two codes are compared and validated against the results from the experiments. The numerical results were able to confirm a suspicion that the cross flow in the feeding plenum causes an observed non-symmetry of the measured film cooling effectiveness at the outlet of some cooling holes

Posterior fossa tumors in children: Radiological tips &amp; tricks in the age of genomic tumor classification and advance MR technology

International audienc

[Pneumatic tube system for blood products transport].

International audienceBlood product transport from blood bank to the patient care areas of hospitals is a key step in the transfusion process. The pneumatic tube system is now widely used in hospitals. Strict performance specifications must be respected to guarantee blood safety: robustness, easy to use and respect the constraints imposed to blood products. To secure the disposal of blood products ordered to a carrier (delivery step), a security device must be deployed (video camera, barcode reading, fax, chip), allowing in particular to limit the risk of addressing error when sending (in the case of device with several arrival stations) or picked up by the wrong carrier

Urokinase receptor (uPAR, CD87) is a platelet receptor important for kinetics and TNF-induced endothelial adhesion in mice

BACKGROUND: Urokinase plasminogen activator receptor (uPAR, CD87) is a widely distributed 55-kD, glycoprotein I-anchored surface receptor. On binding of its ligand uPA, it is known to increase leukocyte adhesion and traffic. Using genetically deficient mice, we explored the role of uPAR in platelet kinetics and TNF-induced platelet consumption. METHODS AND RESULTS: Anti-uPAR antibody stained platelets from normal (+/+) but not from uPAR-/- mice, as seen by fluorescence-activated cell sorter analysis. 51Cr-labeled platelets from uPAR-/- donors survived longer than those from +/+ donors when injected into a +/+ recipient. Intratracheal TNF injection induced thrombocytopenia and a platelet pulmonary localization, pronounced in +/+ but absent in uPAR-/- mice. Aprotinin, a plasmin inhibitor, decreased TNF-induced thrombocytopenia. TNF injection markedly reduced the survival and increased the pulmonary localization of 51Cr-labeled platelets from +/+ but not from uPAR-/- donors, indicating that it is the platelet uPAR that is critical for their response to TNF. As seen by electron microscopy, TNF injection increased the number of platelets and polymorphonuclear neutrophils (PMNs) in the alveolar capillaries of +/+ mice, whereas in uPAR-/- mice, platelet trapping was insignificant and PMN trapping was slightly reduced. Platelets within alveolar capillaries of TNF-injected mice were activated, as judged from their shape, and this was evident in +/+ but not in uPAR-/- mice. CONCLUSIONS: These results demonstrate for the first time the critical role of platelet uPAR for kinetics as well as for activation and endothelium adhesion associated with inflammation

Impact on child and parent anxiety level of a teddy bear-scale mock magnetic resonance scanner

International audienc

A role for lymphotoxin beta receptor in host defense against Mycobacterium bovis BCG infection

To investigate the role of membrane lymphotoxin (LT)alpha1 / beta2 and its LTbeta receptor (LTbetaR) in the protective immune response to Mycobacterium bovis bacillus Calmette-Guerin (BCG) infection, we have used a soluble fusion molecule (LTbetaR-IgG1). LTbetaR-Ig treatment interferes with granuloma formation mainly in the spleen by inhibiting macrophage activation and nitric oxide synthase activity. In addition, a large accumulation of eosinophils was observed in the spleen of LTbetaR-Ig-treated infected mice. Decreased blood levels of IFN-gamma and increased IL-4 were also observed, suggesting that the LTbetaR pathway is important in BCG infection to favor a Th1 type of immune response. The treatment of transgenic mice expressing high blood levels of a soluble TNFR1-IgG3 fusion protein with LTbetaR-Ig resulted in a still higher sensitivity to BCG infection, and extensive necrosis in the spleen. In conclusion, these results suggest that the LTbetaR and the TNFR pathways are not redundant in the course of BCG infection and protective granuloma formation: the LTbetaR pathway appears to be important in spleen granuloma formation, whereas the TNFR pathway has a predominant role in other tissues