92 research outputs found
Wind climate micro-zoning: A pilot application to Liguria Region (North-Western Italy), Journal of Wind Engineering and Industrial Aero-dynamics,.
Immune-based therapies in pancreatic and colorectal cancers and biomarkers of responsiveness
Immune-based strategies are the most promising treatments to improve cancer disease control. Early clinical trials are ongoing to test the safety and feasibility of immune-based therapies for gastrointestinal cancers. However, to date, immunotherapy has been only an experimental option for these diseases and a better understanding of their molecular, cellular, structural and clinical dissimilarities is crucial in the generation of tailored immunotherapeutic treatments. In this review, we will summarize the key mechanisms that regulate the action of immune system in cancer and the different immune-based approaches aimed at improving disease control in patients with advanced disease. We will then move on to discussing the current immunotherapeutic approaches in two types of gastrointestinal (colo-rectal and pancreatic) cancers, whose immune microenvironment has been lately object of intense analyses and has emerged as an important determinant of clinical outcome
Tertiary lymphoid tissue in the tumor microenvironment : from its occurrence to immunotherapeutic implications
Recruitment of immune and inflammatory cells in the microenvironment of solid tumors is highly heterogeneous and follows patterns, varying according to the organ of origin and stage of disease, with critical roles in the process of cancer onset and progression. While adaptive cells are endowed with anti-tumor activities, inflammatory components of the immune infiltrate orchestrate an immunosuppressive microenvironment that reveals ambivalent functions of the immune contexture in the tumor milieu. The balance between opposing pro-tumoral and anti-tumoral immune pathways, which occur concomitantly in the tumor microenvironment, and the regulatory networks of these phenomena have been the target of several immunotherapeutic strategies. While the scarcity of adaptive immune effectors in tumors correlates with dismal prognosis, the pathways of activation of tumor-specific lymphocytes are yet to be fully elucidated. Recently, the occurrence of tertiary lymphoid tissue was revealed to be critical in mediating the dynamics of T cell recruitment and local activation of immune cells in the tumor microenvironment. Thus, tertiary lymphoid tissue assessment and targeting emerge as a promising approach for the design of novel prognostic immune signatures and immunotherapeutic strategies. The immunological behavior of tertiary lymphoid tissue, its occurrence in the tumor immune microenvironment and its clinical relevance are discussed here
Atmospheric dynamics of extreme discharge events from 1979 to 2016 in the southern Central Andes
During the South-American Monsoon season, deep convective systems occur at the eastern flank of the Central Andes leading to heavy rainfall and flooding. We investigate the large- and meso-scale atmospheric dynamics associated with extreme discharge events (> 99.9th percentile) observed in two major river catchments meridionally stretching from humid to semi-arid conditions in the southern Central Andes. Based on daily gauge time series and ERA-Interim reanalysis, we made the following three key observations: (1) for the period 1940–2016 daily discharge exhibits more pronounced variability in the southern, semi-arid than in the northern, humid catchments. This is due to a smaller ratio of discharge magnitudes between intermediate (0.2 year return period) and rare events (20 year return period) in the semi-arid compared to the humid areas; (2) The climatological composites of the 40 largest discharge events showed characteristic atmospheric features of cold surges based on 5-day time-lagged sequences of geopotential height at different levels in the troposphere; (3) A subjective classification revealed that 80% of the 40 largest discharge events are mainly associated with the north-northeastward migration of frontal systems and 2/3 of these are cold fronts, i.e. cold surges. This work highlights the importance of cold surges and their related atmospheric processes for the generation of heavy rainfall events and floods in the southern Central Andes.Fil: Castino, F.. Universitat Potsdam; AlemaniaFil: Bookhagen, B.. Universitat Potsdam; AlemaniaFil: de la Torre, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Austral. Facultad de Ingeniería. Departamento de Ciencias Básicas; Argentin
The Expression of Prolactin and its Cathepsin D-mediated Cleavage in the bovine Corpus luteum vary with the Oestrous cycle
Copyright © 2007 by the American Physiological Society.In the corpus luteum (CL), blood vessels develop, stabilize, and regress. This depends on the ratio of pro- and anti-angiogenic factors, which change during the ovarian cycle. The present study focuses on the possible roles of 23-K prolactin (PRL) in the bovine CL and its anti-angiogenic N-terminal fragments after extracellular cleavage by cathepsin D (Cath D). Prolactin RNA and protein were demonstrated in the CL tissue, in luteal endothelial cells and steroidogenic cells. Cath D was detected in CL tissue, cell extracts and corresponding cell supernatants. In the intact CL, 23-K PRL levels decreased gradually, whereas Cath D levels concomitantly increased between early to late luteal stages. In vitro, PRL cleavage occurred in the presence of acidified homogenates of CL tissue, cells and corresponding cell supernatants. Similar fragments were obtained with purified Cath D, and their appearance was inhibited by pepstatin A. The aspartic protease specific substrate MOCAc-GKPILF~FRLK(Dnp)-D-R-NH2 was cleaved by CL cell supernatants, providing further evidence for Cath D activity. 16-K PRL inhibited proliferation of luteal endothelial cells accompanied by an increase in cleaved caspase-3. In conclusion: (1) The bovine CL is able to produce PRL and to process it into anti-angiogenic fragments by Cath D activity. (2) PRL cleavage might mediate angioregression during luteolysis.Sabine Erdmann, Albert Markus Ricken, Claudia Merkwitz, Ingrid Struman, Castino Roberta, Katja Hummitzsch, Frank Gaunitz, Ciro Isidoro, Joseph Martial and Katharina Spanel-Borowsk
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