1,527 research outputs found

    Search for a Standard Model H→ττ→ℓτh with the ATLAS detector in pp collisions at 7 TeV

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    The results for a search of a SM Higgs that decays to two taus, where one tau decays leptonically and the other hadronically in ATLAS data at 7TeV, corresponding to a luminosity of 4.7 fb−1, are presented. The number of observed events is consistent with the background estimation. Exclusion limits on the production cross section multiplied by the branching ratio are derived as a function of the Higgs mass

    SPARC is a new myeloid-derived suppressor cell marker licensing suppressive activities

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    Myeloid-derived suppressor cells (MDSC) are well-known key negative regulators of the immune response during tumor growth, however scattered is the knowledge of their capacity to influence and adapt to the different tumor microenvironments and of the markers that identify those capacities. Here we show that the secreted protein acidic and rich in cysteine (SPARC) identifies in both human and mouse MDSC with immune suppressive capacity and pro-tumoral activities including the induction of epithelial-to-mesenchymal transition (EMT) and angiogenesis. In mice the genetic deletion of SPARC reduced MDSC immune suppression and reverted EMT. Sparc−/− MDSC were less suppressive overall and the granulocytic fraction was more prone to extrude neutrophil extracellular traps (NET). Surprisingly, arginase-I and NOS2, whose expression can be controlled by STAT3, were not down-regulated in Sparc−/− MDSC, although less suppressive than wild type (WT) counterpart. Flow cytometry analysis showed equal phosphorylation of STAT3 but reduced ROS production that was associated with reduced nuclear translocation of the NF-kB p50 subunit in Sparc−/− than WT MDSC. The limited p50 in nuclei reduce the formation of the immunosuppressive p50:p50 homodimers in favor of the p65:p50 inflammatory heterodimers. Supporting this hypothesis, the production of TNF by Sparc−/− MDSC was significantly higher than by WT MDSC. Although associated with tumor-induced chronic inflammation, TNF, if produced at high doses, becomes a key factor in mediating tumor rejection. Therefore, it is foreseeable that an unbalance in TNF production could skew MDSC toward an inflammatory, anti-tumor phenotype. Notably, TNF is also required for inflammation-driven NETosis. The high level of TNF in Sparc−/− MDSC might explain their increased spontaneous NET formation as that we detected both in vitro and in vivo, in association with signs of endothelial damage. We propose SPARC as a new potential marker of MDSC, in both human and mouse, with the additional feature of controlling MDSC suppressive activity while preventing an excessive inflammatory state through the control of NF-kB signaling pathway

    Assessing the potential of molten carbonate fuel cell-based schemes for carbon capture in natural gas-fired combined cycle power plants

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    Abstract This work explores two configurations of natural gas-fired combined cycles (NGCC) with molten carbonate fuel cells (MCFC) for CO2 capture. Special attention is devoted to the selection of MCFC operating conditions (trade-off between CO2 capture and voltage losses), heat integration scheme, fuel use and CO2 purification. Two schemes are considered: (i) in the first "integrated" scheme, MCFC modules are installed between the gas turbine and the heat recovery steam generator (HRSG) to maximize the efficiency of the integrated power plant; (ii) in the second "non-integrated" layout, the MCFC is located downstream of the HRSG and a regenerative heat exchanger is designed to preheat cathode reactants up to the MCFC working temperature. This study includes a full techno-economic analysis of the two layouts based on a preliminary sizing of the key-components, and a sensitivity analysis on the CO2 utilization factor. Compared to a benchmark amine scrubbing process, the "integrated" configuration shows considerably better performance (Specific Primary Energy Consumption for CO2 Avoided - SPECCA = 0.31 MJ kgCO2-1; Cost of CO2 avoided - CCA = 50 tCO2−1),whereasthe"non−integrated"solutionshowshigherenergypenaltiesbutsimilarCO2avoidancecost(SPECCA = 2.4 MJ kgCO2−1;CCA = 76 tCO2−1), whereas the "non-integrated" solution shows higher energy penalties but similar CO2 avoidance cost (SPECCA = 2.4  MJ  kgCO2−1; CCA = 76 tCO2−1)

    Overexpression of Osmyb4 enhances compatible solute accumulation and increases stress tolerance of arabidopsis thaliana

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    In this paper, we report the metabolic and molecular changes in response to cold and drought induced in Osmyb4 transgenic Arabidopsis thaliana compared with the wildtype (WT). The rice Osmyb4 gene codes for a transcription factor (Myb4) induced by cold treatment and, in Arabidopsis transgenic plants, improves cold and freezing tolerance [Vannini C, Locatelli F, Bracale M, Magnani E, Marsoni M, Osnato M, Mattana M, Baldoni E, Coraggio I (2004) Plant J 37: 115-127]. Here, we report the ability of Myb4 to induce also drought tolerance in Arabidopsis transgenic plants. By the use of nuclear magnetic resonance (NMR) and enzymatic assays, we showed that several compatible solutes (glucose, fructose, sucrose, proline, glycine betaine and sinapoyl malate) accumulate in higher amount in Osmyb4-overexpressing plants with respect to the WT, both under normal and stress conditions. Considering proline, we also found that in transgenic plants the levels of the mRNAs coding for \u3941- pyrroline-5-carboxylate synthase (EC not assigned) and for \u3941- pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12) were higher and lower, respectively. The constitutive activation of several stress-inducible pathways and different kinetics in the accumulation of several metabolites, in Myb4 transgenic plants, may represent an advantage to prepare plants to face the stress condition. Moreover, these results taken together suggest that Myb4 integrates the activation of multiple components of stress response

    Biological monitoring of occupational exposure to metals in electric steel foundry workers and its contribution to 8-oxo-7,8-dihydro-2′-deoxyguanosine levels

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    In this study, the urinary concentrations of selected metals in workers from an electric steel foundry in Tunisia were assessed and compared with existing biological limit values and general population reference values. Moreover, the association between oxidative DNA damage, measured as urinary 8-oxo-7,8-dihydro-2\u2019deoxyguanosine (8-oxodG) and co-exposure to metals and polycyclic aromatic hydrocarbons (PAHs) was evaluated. Urinary levels of 12 metals were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in end-shift spot samples from 89 workers. The urinary levels of phenanthrene (U-PHE), as marker of exposure to PAHs, and 8-oxodG were also available. Median levels ranged from 0.4 \ub5g/L (cobalt, Co, and thallium, Tl) to 895 \ub5g/L (zinc, Zn). Only 1% of samples was above the biological limit values for Co, and up to 13.5% of samples were above limit values for Cd. From 3.4% (Co) to 72% (lead, Pb) of samples were above the reference values for the general population. Multiple linear regression models, showed that manganese (Mn), Zn, arsenic (As), barium (Ba), Tl, and Pb were significant predictors of 8-oxodG (0.012 64 p 64 0.048); U-PHE was also a significant predictor (0.003 64 p 64 0.059). The variance explained by models was low (0.11 64 R2 64 0.17, p < 0.005), showing that metals and PAHs were minor contributors to 8-oxodG. Overall, the comparison with biological limit values showed that the study subjects were occupationally exposed to metals, with levels exceeding biological limit values only for Cd

    Myeloid-derived suppressor cells: Ductile targets in disease

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    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells with major regulatory functions and rise during pathological conditions, including cancer, infections and autoimmune conditions. MDSC expansion is generally linked to inflammatory processes that emerge in response to stable immunological stress, which alter both magnitude and quality of the myelopoietic output. Inability to reinstate physiological myelopoiesis would fall in an "emergency state" that perpetually reprograms myeloid cells toward suppressive functions. While differentiation and reprogramming of myeloid cells toward an immunosuppressive phenotype can be considered the result of a multistep process that originates in the bone marrow and culminates in the tumor microenvironment, the identification of its driving events may offer potential therapeutic approaches in different pathologies. Indeed, whereas expansion of MDSCs, in both murine and human tumor bearers, results in reduced immune surveillance and antitumor cytotoxicity, placing an obstacle to the effectiveness of anticancer therapies, adoptive transfer of MDSCs has shown therapeutic benefits in autoimmune disorders. Here, we describe relevant mechanisms of myeloid cell reprogramming leading to generation of suppressive MDSCs and discuss their therapeutic ductility in disease

    Metal(loid)s role in the pathogenesis of amyotrophic lateral sclerosis: Environmental, epidemiological, and genetic data

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    Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disorder of the motor system. The etiology is still unknown and the pathogenesis remains unclear. ALS is familial in the 10% of cases with a Mendelian pattern of inheritance. In the remaining sporadic cases, a multifactorial origin is supposed in which several predisposing genes interact with environmental factors. The etiological role of environmental factors, such as pesticides, exposure to electromagnetic fields, and metals has been frequently investigated, with controversial findings. Studies in the past two decades have highlighted possible roles of metals, and ionic homeostasis dysregulation has been proposed as the main trigger to motor-neuron degeneration. This study aims at evaluating the possible role of environmental factors in etiopathogenesis of ALS, with a particular attention on metal contamination, focusing on the industrial Briga area in the province of Novara (Piedmont region, North Italy), characterized by: i) a higher incidence of sporadic ALS (sALS) in comparison with the entire province, and ii) the reported environmental pollution. Environmental data from surface, ground and discharge waters, and from soils were collected and specifically analyzed for metal content. Considering the significance of genetic mechanisms in ALS, a characterization for the main ALS genes has been performed to evaluate the genetic contribution for the sALS patients living in the area of study. The main findings of this study are the demonstration that in the Briga area the most common metal contaminants are Cu, Zn, Cr, Ni (widely used in tip-plating processes), that are above law limits in surface waters, discharge waters, and soil. In addition, other metals and metalloids, such as Cd, Pb, Mn, and As show a severe contamination in the same area. Results of genetic analyses show that sALS patients in the Briga area do not carry recurrent mutations or an excess of mutations in the four main ALS causative genes (SOD1, TARDBP, FUS, C9ORF72) and for ATXN2 CAG repeat locus. This study supports the hypothesis that the higher incidence of sALS in Briga area may be related to environmental metal(loid)s contamination, along with other environmental factors. Further studies, implementing analysis of genetic polymorphisms, as well as investigation with long term follow-up, may yield to key aspects into the etiology of ALS. The interplay between different approaches (environmental, chemical, epidemiological, genetic) of our work provides new insights and methodology to the comprehension of the disease etiology

    Characterization of the biogenic volatile organic compounds (BVOCs) and analysis of the PR1 molecular marker in Vitis vinifera L. inoculated with the nematode Xiphinema index

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    Upon pathogen attack, plants very quickly undergo rather complex physico-chemical changes, such as the production of new chemicals or alterations in membrane and cell wall properties, to reduce disease damages. An underestimated threat is represented by root parasitic nematodes. In Vitis vinifera L., the nematode Xiphinema index is the unique vector of Grapevine fanleaf virus, responsible for fanleaf degeneration, one of the most widespread and economically damaging diseases worldwide. The aim of this study was to investigate changes in the emission of biogenic volatile organic compounds (BVOCs) in grapevines attacked by X. index. BVOCs play a role in plant defensive mechanisms and are synthetized in response to biotic damages. In our study, the BVOC profile was altered by the nematode feeding process. We found a decrease in \u3b2-ocimene and limonene monoterpene emissions, as well as an increase in \u3b1-farnesene and \u3b1-bergamotene sesquiterpene emissions in nematode-treated plants. Moreover, we evaluated the PR1 gene expression. The transcript level of PR1 gene was higher in the nematode-wounded roots, while in the leaf tissues it showed a lower expression compared to control grapevines
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