SURFACE PARAMETERS EVALUATED FROM SATELLITE REMOTE SENSING IMAGES FOR POLLUTANT ATMOSPHERIC DISPERSION MODELLING

This contribute deals with the use of surface parameters extracted from satellite remote sensing images for the setup of the input dataset required by pollutants atmospheric dispersion models (PATM). These models need 2D distributions (grids) of many surface parameters to model turbulence parameters, as roughness length, albedo, leaf area index and Bowen ratio. Very often these parameters are set using predefined tables defined as a function of land cover (LC). Usually, this last information is extracted from public datasets, such as, for European countries, the CORINE Land Cover (CLC). Some of these parameters can be computed directly from remote sensing. Moreover, land cover classification evaluated from remote sensing can be used to update existing LC datasets. In this work ASTER images have been used to evaluate, using a supervised classification method, the LC map of the area. This LC is used to update the CLC. Moreover, albedo was directly calculated from the image. The importance of information extracted from remote sensing is evaluated using the SPRAY lagrangian PATM. SPRAY has been used to simulate the dispersion of an inert generic pollutant emitted from two virtual sources on a 30 km x 40 km domain in a study area located at Venice (Northern Italy), where a big industrial site is found (Porto Marghera). Real (measured) meteorological data have been used

Foodborne Salmonellosis in Italy: Characterization of Salmonella enterica Serovar Typhimurium and Monophasic Variant 4,[5],12:i- Isolated from Salami and Human Patients.

Salmonella enterica serovar Typhimurium (STm) and its monophasic variant 4,[5],12:i:- (VMSTm) have been responsible for an increased number of foodborne infections in humans in Europe in recent years. The aim of this study was to investigate the origin of three foodborne salmonellosis outbreaks that occurred in Pavia Province (Lombardy region, northern Italy) in 2010. Phenotypic and genetic characteristics of the STm and VMSTm isolates from patients and from food that were recovered in the framework of the three outbreaks were evaluated through serotyping, phage typing, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE), and multiple-locus variable-number tandem repeat analysis (MLVA). Salami from three artisan producers, which had all purchased meat from the same slaughterhouse, was the food source of infection in outbreak I. STm isolates were recovered from salami and patients with symptoms of gastroenteritis. These isolates had the same PFGE type and the same rare MLVA profile (3-18-9-NA-211). The same molecular profiles were found in an STm isolate from a salami, which likely was the source of another family outbreak (II). A VMSTm strain with common phenotypic and molecular profiles was isolated from three hospitalized patients and identified as the cause of another putative outbreak (III). During the following 3 years (2011 through 2013), 360 salami produced in Pavia Province were monitored for the presence of S. enterica . In 2011, no STm and VMSTm isolates were recovered from 159 salami tested. During 2012 and 2013, 13.9% of 201 tested salami harbored S. enterica , and half of the isolates were VMSTm, mainly in salami from those artisan producers involved in the previous outbreaks. These isolates were genetically variable, especially in terms of MLVA profiles. The data collected suggest that from 2012, VMSTm has replaced STm in the environments of the salami producers monitored in this study, and these data confirm the dominance of this emergent serovar along the pork supply chain

Clonal heterogeneity in chronic lymphocytic leukemia cells: superior response to surface IgM cross-linking in CD38, ZAP-70-positive cells.

Background Patients with chronic lymphocytic leukemia whose cells express CD38 and ZAP-70 and utilize unmutated Ig VH region genes have a very poor prognosis. We studied whether cells expressing CD38 and ZAP-70 are more susceptible to stimulation through B-cell receptors than are cells that do not express CD38 and ZAP-70.Design and Methods CD38-positive and CD38-negative leukemic cells were separated from single cases and compared for their response to B-cell receptor cross-linking and ZAP-70 expression. Cohort studies were also carried out by measuring the apoptotic response to surface immunoglobulin M (IgM) cross-linking in 82 patients with chronic lymphocytic leukemia and the protein tyrosine phosphorylation induced by surface IgM in 21 patients.Results CD38-positive cells, isolated from cases of chronic lymphocytic leukemia classified as CD38-positive or CD38-negative, expressed more ZAP-70 than the corresponding CD38-negative cells, exhibited more robust protein tyrosine phosphorylation and had a greater tendency to apoptosis upon B-cell receptor cross-linking. In the cohort studies, surface IgM-induced protein tyrosine phosphorylation correlated significantly with CD38 and ZAP-70 expression and with the absence of Ig VH gene mutations. Apoptosis induced by surface IgM cross-linking correlated significantly only with the proportion of CD38-positive cells. Difficulties in finding more definitive correlations were probably related to imprecision in the in vitro test system and in the definition of cases as positive or negative.Conclusions Collectively, these data indicate that CD38-positive, ZAP-70-positive cells have a greater capacity for signaling through the B-cell receptor and suggest a function for B-cell receptor signaling in promoting chronic lymphocytic leukemia cell expansion, especially within the CD38-positive fraction of the leukemic clone

Selective Arylsulfonamide Inhibitors of ADAM-17: Hit Optimization and Activity in Ovarian Cancer Cell Models

Activated Leukocyte Cell Adhesion Mol. (ALCAM) is expressed at the surface of epithelial ovarian cancer (EOC) cells and is released in a sol. form (sALCAM) by ADAM-17-mediated shedding. This process is relevant to EOC cell motility and invasiveness, which is reduced by inhibitors of ADAM-17. In addn., ADAM-17 plays a key role in EGFR signalling and thus may represent a useful target in anticancer therapy. Herein we report our hit optimization effort to identify potent and selective ADAM-17 inhibitors, starting with previous mol. 1. A new series of secondary sulfonamido-based hydroxamates was designed and synthesized. The biol. activity of the newly synthesized compds. was tested in vitro on isolated enzymes and human EOC cell lines. The optimization process led to compd. 21, which showed an IC50 of 1.9 nM on ADAM-17 with greatly increased selectivity. This compd. maintained good inhibitory properties on sALCAM shedding in several in vitro assays

human renal cancer cells express a novel membrane bound interleukin 15 that induces in response to the soluble interleukin 15 receptor α chain epithelial to mesenchymal transition

Although interleukin-15 (IL-15) is a powerful immunomodulatory factor that has been proposed for cancer immunotherapy, its intratumoral expression may be correlated with tumor progression and/or poor clinical outcome. Therefore, neoplasias potentially sensitive to immunotherapy should be checked for their IL-15 expression and function before choosing immunotherapy protocols. Primary human renal cancer cells (RCC) express a novel form of membrane-bound IL-15 (mb-IL-15), which displays three major original properties: (a) It is expressed as a functional membrane homodimer of 27 kDa, (b) it is shed in the extracellular environment by the metalloproteases ADAM17 and ADAM10, and (c) its stimulation by soluble IL-15 receptor α (s-IL-15Rα) chain triggers a complex reverse signal (mitogen-activated protein kinases, FAK, pMLC) necessary and sufficient to ~induce epithelial-mesenchymal transdifferentiation (EMT), a crucial process in tumor progression whose induction is unprecedented for IL-15. In these cells, complete EMT is characterized by a dynamic reorganization of the cytoskeleton with the subsequent generation of a mesenchymal/contractile phenotype (α-SMA and vimentin networks) and the loss of the epithelial markers E-cadherin and ZO-1. The retrosignaling functions are, however, hindered through an unprecedented cytokine/receptor interaction of mb-IL-15 with membrane-associated IL-15Rα subunit that tunes its signaling potential competing with low concentrations of the s-IL-15Rα chain. Thus, human RCC express an IL-15/IL-15R system, which displays unique biochemical and functional properties that seem to be directly involved in renal tumoral progression. [Cancer Res 2009;69(4):1561–9

Microenvironment regulation of the IL-23R/IL-23 axis overrides chronic lymphocytic leukemia indolence

The development and progression of Chronic Lymphocytic Leukemia (CLL) require co-operation of both microenvironment and cytokines. Investigating the IL-23R/IL-23 axis we found that circulating cells of early-stage CLL patients with shorter time-to-treatment (but not of those with a more benign course) expressed a defective form of the IL-23R complex lacking the IL-12Rß1 chain. However, the cells from both patient groups expressed the com-plete IL-23R complex in tissue infiltrates and could be induced to express it when co-cultured with activated T cells or other CD40L-bearing cells. IL-23 production by CLL cells activated in vitro in this fashion and in lymphoid tissues was observed suggesting the exist-ence of an autocrine/paracrine loop causing CLL cell proliferation. Culture of CLL cells with stromal cells, nurse like cells and stimulation with anti IgM antibodies and IL-4 failed to activate this loop. Interference with the IL-23R/IL-23 axis using an anti-IL-23p19 anti-body proved effective in controlling disease onset/expansion in xenografted mice, suggest-ing potential therapeutic strategies