1,720,971 research outputs found

    The Role of ICOS/OPN/ICOSL System in Wound Healing, Sepsis and Cancer

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    ICOS (also known as CD278) is a T cell co-stimulatory molecule, a member of the CD28 family. It wasoriginally identified on activated T cells, but it has been recently detected also in dendritic cells andmacrophages.ICOS binds ICOSL (or B7h), a member of the B7 family. ICOSL is expressed by multiple cell types, such asantigen presenting cells (APC), endothelial cells, epithelial cells, fibroblasts and several types of neoplasticcells. The interaction of ICOSL and ICOS can induce the transmission of “reverse signals” in the cell thatexpresses ICOSL. Moreover, recent data showed that also OPN (Osteopontin) binds ICOSL using a differentbinding site than that used by ICOS and elicits different, often opposite, effects in the immune response,tumor development, and bone metabolism. In particular, ICOSL triggering using a recombinant soluble formof ICOS (ICOS-Fc) inhibits tumor cell migration, tumor angiogenesis, and tumor growth, which are increasedby OPN. Moreover, ICOS-Fc inhibits bone resorption mediated by osteoclasts, whereas OPN is involved inbone deposition.Aim of this thesis was to assess the role of the ICOS/ICOSL interaction in tumor development, working onmultiple myeloma and melanoma; and the relative role in the inflammatory and repair phases ofinflammation, working in skin wound healing and sepsis.1) Multiple myeloma was chosen because it is a bone tumor in which the ICOS/ICOSL interaction mayinfluence both the tumor growth and the osteolytic lesions. Results show that that multiple myeloma cellsexpress high levels of ICOSL and low levels of ICOS, and patients with multiple myeloma display increasedserum levels of soluble forms of both molecules correlating with known parameters of tumor burden.Moreover, treatment of mice with ICOS-Fc loaded in biocompatible biodegradable PLGA nanoparticlesinhibits the growth of myeloma cells in vivo, exerting a predominant anti-angiogenic effect.2) Melanoma was chosen because previous data showed that treatment of mice with ICOS-Fc loaded onPLGA or cyclodextrin nanoparticles strongly inhibits tumor growth and metastatization, and exerts anti-angiogenic effects. Using the B16 mouse melanoma model, we investigated the possibility of using ICOS-Fcin a combination therapy where ICOS-Fc was loaded in Intralipid® nanoemulsions together with thetargeted drug sorafenib, and the chemotherapeutic drug temozolomide. Results show that the combinationtherapy strongly inhibits the tumor growth and angiogenesis, and a key role is played by ICOS-Fc.3) Skin wound healing was chosen because it is a physiologic process in which the inflammatory and therepair phases of inflammation can be easily monitored in mice. Results show that local treatment withICOS-Fc improves wound healing, promotes angiogenesis, preceded by upregulation of IL-6 and VEGFexpression; increases the number of fibroblasts and T cells, whereas it reduces that of neutrophils; andincreases the number of M2 vs. M1 macrophages.4) Sepsis was chosen because it is a pathologic process due to excessive and uncoordinated development ofthe inflammatory and the repair phase of inflammation. Results show that, in sepsis induced by cecalligation and puncture (CLP) in mice, treatment with ICOS-Fc reduces the clinical severity score, plasmacytokines, liver injury, and kidney dysfunction.These data suggest that ICOS-mediated triggering of ICOSL may play a key role in the repair phase ofinflammation, and short circuits of this interaction may be involved in tumor development

    Role of Alginates Combined with Natural Extracts to Prevent the Gastric Acid-Related Damage

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    The human stomach is extremely vulnerable to various attacks able to cause erosion and mucosal epithelium damage which lead to gastrointestinal tract bleeding and/or ulcer perforations and finally worsen the original disease. A prolonged exposition to strong acidic environment causes coagulation necrosis resulting from the desiccating action of the acid on proteins in exposed tissues with inflammation and accumulation of intracellular radical oxygen species. Therapeutic strategies aim to treat both symptoms and epithelial damage with chemical or mechanical approaches. In this context, alginates seem to have great importance, especially if combined with other molecules known to have some properties on gastric epithelial cells, for example, vitamin D3, extract of prickly pear and olive leaves, and a tyndalized probiotic. This natural composition is able to exert a gastroprotective effect to maintain or restore the integrity of gastric epithelium through an antioxidant pathway, inhibiting apoptosis and activating survival kinases better than other pharmacological or natural active principle

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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