1,720,967 research outputs found
A NOVEL SELECTIVE INHIBITOR FOR PLASMA MEMBRANE CALCIUM ATPase 4 IMPROVES VEGF-MEDIATED ANGIOGENESIS
Get PDFA thesis submitted in fulfilment of the requirement of the
University of Wolverhampton for the degree of Doctor of Philosophy.Ischaemic cardiovascular diseases are the leading cause of death worldwide. Therapeutic angiogenesis provides a valuable tool to treat these conditions by stimulating the growth of new blood vessels in the ischaemic tissue. The pro-angiogenic factor VEGF is the most potent inducer of angiogenesis, and exogenous delivery of VEGF has been a key element of therapeutic strategies. Unfortunately, VEGF-based pro-angiogenic procedures have produced only limited patient benefit. Failure to restore efficient VEGF activity remains a major problem. VEGF-mediated activation of the calcineurin/NFAT signalling pathway has been identified as a crucial regulator of angiogenesis. Our laboratory has recently shown a novel role for the plasma membrane calcium ATPase 4 (PMCA4) protein as a negative regulator of VEGF-induced angiogenesis via interaction with calcineurin. The recent identification of aurintricarboxylic acid (ATA) as a selective inhibitor of PMCA4 prompted us to hypothesise that inhibition of PMCA4 with ATA should enhance VEGF-induced angiogenesis. Here, we show that treatment of endothelial cells with nanomolar concentrations of ATA notably enhances calcineurin/NFAT signalling by disrupting the PMCA4/calcineurin interaction. ATA mediated inhibition of PMCA4 results in a significant increase in endothelial cell motility and in vitro and in vivo blood vessel formation. Low concentrations of ATA do not have any deleterious effects on the viability of endothelial cells or zebrafish embryonic development. However, high ATA concentrations impaired endothelial cell viability, and were associated with toxicity in zebrafish embryos. This study highlights the potential of targeting PMCA4 to improve VEGF-based pro-angiogenic therapeutic strategies. This goal will require the development of refined versions of ATA without associated toxicity, or the identification of novel PMCA4 inhibitors
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Poly-Gamma-Glutamic Acid (γ-PGA)-based encapsulation of Adenovirus to evade neutralizing antibodies.
Get PDFIn recent years, there has been an increasing interest in oncolytic adenoviral vectors as an alternative anticancer therapy. The induction of an immune response can be considered as a major limitation of this kind of application. Significant research efforts have been focused on the development of biodegradable polymer poly-gamma-glutamic acid (γ-PGA)-based nanoparticles used as a vector for effective and safe anticancer therapy, owing to their controlled and sustained-release properties, low toxicity, as well as biocompatibility with tissue and cells. This study aimed to introduce a specific destructive and antibody blind polymer-coated viral vector into cancer cells using γ-PGA and chitosan (CH). Adenovirus was successfully encapsulated into the biopolymer particles with an encapsulation efficiency of 92% and particle size of 485 nm using the ionic gelation method. Therapeutic agents or nanoparticles (NPs) that carry therapeutics can be directed specifically to cancerous cells by decorating their surfaces using targeting ligands. Moreover, in vitro neutralizing antibody response against viral capsid proteins can be somewhat reduced by encapsulating adenovirus into γ-PGA-CH NPs, as only 3.1% of the encapsulated adenovirus was detected by anti-adenovirus antibodies in the presented work compared to naked adenoviruses. The results obtained and the unique characteristics of the polymer established in this research could provide a reference for the coating and controlled release of viral vectors used in anticancer therapy.This work was funded by the Ministry of Higher Education and Scientific Research (Iraq). This work was also partially funded by the Research Investment Fund, University of Wolverhampton (Wolverhampton, United Kingdom) and the Italian Ministry of University and Research (MIUR)
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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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