1,720,959 research outputs found

    The role of myeloid CSF-1 receptor (CSF-1R) in mesothelioma cell proliferation

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    Colony-stimulating factor 1 receptor (CFS-1R) is a myeloid receptor with a key role in monocyte survival and proliferation. Its overexpression is associated with aggressive tumor characterized by a tumor microenvironment enriched of M2-like tumor-associated macrophages as well as drug resistance and poor prognosis. Recently, CSF-1R was detected on cancer cell surface in different solid tumors, capturing the interest of various research group interested in investigating the role of this receptor in non-myeloid cells. Malignant Mesothelioma is an aggressive tumor of the pleura and peritoneum, characterized by minimal clinical manifestations and few therapeutic options. Because the molecular mechanisms leading to mesothelioma carcinogenesis are unique and not fully understood, the tumor is difficult to tackle both diagnostically and therapeutically. Previous research demonstrated that CSF-1R is expressed by mesothelioma cells rather than normal mesothelial cells. Additional studies showed that CSF-1R activation induced mitogenic signaling pathways and the regulation of cell cycle-related factors in both monocytes and tumor cells. The aim of this thesis is to analyze how CSF-1R supported cancer cell proliferation and the investigation of the mechanisms regulating its expression throughout cell cycle phases. The expression of CSF-1R was investigated in different mesothelioma cell lines. Cell synchronization protocols were used to assess the expression of the receptor and its activity in the various cell cycle phases. Results indicated that CSF-1R expression characterized a pool of proliferating cells. We found that CSF-1R, different from other RTKs, undergoes a fine regulation during cell cycle progression. The percentage of CSF-1R+ cells increased in the G1 transition to S phase and in G2-M phase. Additionally, its inhibition negatively affected mitotic entry and G1-S phase transition. In terms of molecular mechanisms, using shRNA interference, we demonstrated that the Retinoblastoma protein (pRb) p105 is required for regulating CSF-1R expression in S-phase. Finally, we demonstrated that the overexpression of the receptor induced the activation of key intracellular pathway promoting cell proliferation including ERK5, ERK1/2 and AKT signaling. Collectively these data described a unique characteristic of CSF-1R which is differentially expressed during cell cycle phases, indicating a fine tuning throughout cell cycle. These findings extend our understanding of CSF-1R role in malignancies, making it a suitable target for an anti-cancer therapy. Further studies are required to evaluate the potential impact of targeting CSF-1R and better understand the mechanisms controlling its activity in cancer

    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

    Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms

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    Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance
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