Meteorologic parameters analysis above Dome C made with ECMWF data

In this paper we present the characterization of all the principal meteorological parameters (wind speed and direction, pressure, absolute and potential temperature) extended over 25 km from the ground and over two years (2003 and 2004) above the Antarctic site of Dome C. The data set is composed by 'analyses' provided by the General Circulation Model (GCM) of the European Center for Medium Weather Forecasts (ECMWF) and they are part of the catalog MARS. A monthly and seasonal (summer and winter time) statistical analysis of the results is presented. The Richardson number is calculated for each month of the year over 25 km to study the stability/instability of the atmosphere. This permits us to trace a map indicating where and when the optical turbulence has the highest probability to be triggered on the whole troposphere, tropopause and stratosphere. We finally try to predict the best expected isoplanatic angle and wavefront coherence time employing the Richardson number maps, the wind speed profiles and simple analytical models of CN2 vertical profiles.Comment: 28 pages, 14 figures, pdf file, to be published on July 2006 - PASP, see also http://www.arcetri.astro.it/~masciad

Donor-But Not Recipient-Derived Cells Produce Collagen-1 in Chronically Rejected Cardiac Allografts

Fibrosis is a prominent feature of chronic allograft rejection, caused by an excessive production of matrix proteins, including collagen-1. Several cell types produce collagen-1, including mesenchymal fibroblasts and cells of hematopoietic origin. Here, we sought to determine whether tissue-resident donor-derived cells or allograft-infiltrating recipient-derived cells are responsible for allograft fibrosis, and whether hematopoietic cells contribute to collagen production. A fully MHC-mismatched mouse heterotopic heart transplantation model was used, with transient depletion of CD4+ T cells to prevent acute rejection. Collagen-1 was selectively knocked out in recipients or donors. In addition, collagen-1 was specifically deleted in hematopoietic cells. Tissue-resident macrophages were depleted using anti-CSF1R antibody. Allograft fibrosis and inflammation were quantified 20 days post-transplantation. Selective collagen-1 knock-out in recipients or donors showed that tissue-resident cells from donor hearts, but not infiltrating recipient-derived cells, are responsible for production of collagen-1 in allografts. Cell-type-specific knock-out experiments showed that hematopoietic tissue-resident cells in donor hearts substantially contributed to graft fibrosis. Tissue resident macrophages, however, were not responsible for collagen-production, as their deletion worsened allograft fibrosis. Donor-derived cells including those of hematopoietic origin determine allograft fibrosis, making them attractive targets for organ preconditioning to improve long-term transplantation outcomes

VLT/NACO Polarimetric Differential Imaging of HD100546 - Disk Structure and Dust Grain Properties between 10-140 AU

We present polarimetric differential imaging (PDI) data of the circumstellar disk around the Herbig Ae/Be star HD100546 obtained with VLT/NACO. We resolve the disk in polarized light in the H and Ks filter between ~0.1-1.4" (i.e., ~10-140 AU). The innermost disk regions are directly imaged for the first time and the mean apparent disk inclination and position angle are derived. The surface brightness along the disk major axis drops off roughly with S(r) ~ r^-3 but has a maximum around 0.15" suggesting a marginal detection of the main disk inner rim at ~15 AU. We find a significant brightness asymmetry along the disk minor axis in both filters with the far side of the disk appearing brighter than the near side. This enhanced backward scattering and a low total polarization degree of the scattered disk flux of 14%(+19%/-8%) suggests that the dust grains on the disk surface are larger than typical ISM grains. Empirical scattering functions reveal the backward scattering peak at the largest scattering angles and a second maximum for the smallest scattering angles. This indicates a second dust grain population preferably forward scattering and smaller in size. It shows that, relatively, in the inner disk regions (40-50 AU) a higher fraction of larger grains is found compared to the outer disk regions (100-110 AU). Finally, our images reveal distinct substructures between 25-35 AU physical separation from the star and we discuss the possible origin for the two features in the context of ongoing planet formation.Comment: Accepted for publication by Ap

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Mid-Infrared Variability in Binary Brown Dwarfs

International audienc

Anti-BAFF Treatment Interferes With Humoral Responses in a Model of Renal Transplantation in Rats

Background. B-cell-activating factor (BAFF) is associated with donor-specific antibodies (DSA) and poorer outcomes after renal transplantation (RTx). We examined the effects of anti-BAFF treatment on B cells, expression of costimulatory molecules and cytokines, germinal centers (GCs), and DSA formation in an RTx model in rats. Methods. Anti-BAFF antibody was injected on days 3, 17, 31, and 45 after allogeneic RTx. Rats received reduced dose cyclosporine A for 28 or 56 days to allow chronic rejection and DSA formation. Leukocytes, B-cell subsets, and DSA were measured using flow cytometry; expression of cytokines and costimulatory molecules was measured by quantitative polymerase chain reaction, and GCs and T follicular helper were assessed using immunohistochemistry. Rejection was evaluated by a nephropathologist. Results. Anti-BAFF treatment reduced the frequency of B cells in allografts and spleen. Naive B cells were strongly reduced by anti-BAFF treatment in all compartments. Messenger RNA expression of interleukin-6 and the costimulatory molecules CD40 and inducible T cell costimulator ligand was significantly reduced in anti-BAFF-treated rats. GC area was smaller and plasmablasts/plasma cell numbers lower in anti-BAFF-treated rats, which was reflected by less DSA in certain IgG subclasses. Conclusions. Anti-BAFF treatment interferes with humoral responses at multiple levels in this model of allogeneic RTx

Effects of Adrenomedullin on the Glomerular Adrenomedullin System in a Rat Model of Anti-Thy1 Glomerulonephritis

Background: Adrenomedullin (ADM) has antiproliferative effects on glomerular mesangial cells. The study was performed to determine changes in glomerular gene expression of the ADM system by ADM treatment in anti-Thy1 glomerulonephritis (GN). Methods: GN in rats was induced by injecting anti-Thy-1 antibody. To show the effect of ADM treatment, rats received ADM from day 3 to day 6 of GN. Supplemental rats were sacrificed on day 3, 7 and 14 of GN to show the expression pattern of adrenomedullin and its receptors. Glomeruli were prepared by sieving or laser-assisted microdissection. Expression of ADM, calcitonin receptor-like receptor (CLR), receptor activity-modifying proteins (RAMP) 1–3, CD34, Thy1 and nephrin was analyzed using real-time PCR. Results: During GN a reduction of CLR and RAMP 2 + 3 expressions was detected on days 3, 7 and 14, while RAMP 1 rose. ADM mRNA decreased on days 3 and 7. Thy1 expression as a surrogate of mesangial cell number was downregulated during GN. A significant reduction of CD34 expression, as a surrogate for endothelial cell number, was detected on day 7. A tendency towards reduction of nephrin gene expression, as a surrogate for number of podocytes, was seen. The administration of ADM during GN did not change the expression on Thy1, CD34 or nephrin. The results were similar for microdissected and sieved glomeruli. In ADM-treated GN animals ADM gene expression rose compared to untreated GN animals on day 6. These effects were detected both in sieved and microdissected glomeruli. ADM administration did not change the expression of the receptors. Conclusion: The downregulation of adrenomedullin during GN at the gene level can be improved by ADM application

Neue Lernziele für das Medizinstudium erarbeitet

Die Digitalisierung hat die Medizin bereits verändert und wird die ärztliche Tätigkeit auch in Zukunft stark beeinflussen. Es ist deshalb wichtig, dass sich angehende Ärztinnen und Ärzte bereits während des Studiums mit den Methoden und Einsatzmöglichkeiten des maschinellen Lernens auseinandersetzen. Die Arbeitsgruppe «Digitalisierung der Medizin» hat dazu Lernziele erarbeitet

Preclinical In Vitro Assessment of Submicron-Scale Laser Surface Texturing on Ti6Al4V

Loosening of orthodontic and orthopedic implants is a critical and common clinical problem. To minimize the numbers of revision surgeries due to peri-implant inflammation or insufficient osseointegration, developments of new implant manufacturing strategies are indicated. Ultrafast laser surface texturing is a promising contact-free technology to modify the physicochemical properties of surfaces toward an anti-infectious functionalization. This work aims to texture Ti6Al4V surfaces with ultraviolet (UV) and green (GR) radiation for the manufacturing of laser-induced periodic surface structures (LIPSS). The assessment of these surface modifications addresses key aspects of topography, morphology and chemical composition. Human primary mesenchymal stromal cells (hMSCs) were cultured on laser-textured and polished Ti6Al4V to characterize the surfaces in terms of their in vitro biocompatibility, cytotoxicity, and metal release. The outcomes of the in vitro experiment show the successful culture of hMSCs on textured Ti6Al4V surfaces developed within this work. Cells cultured on LIPSS surfaces were not compromised in terms of their viability if compared to polished surfaces. Yet, the hMSC culture on UV-LIPSS show significantly lower lactate dehydrogenase and titanium release into the supernatant compared to polished. Thus, the presented surface modification can be a promising approach for future applications in orthodontics and orthopedics