1,720,969 research outputs found
Dataset to support Thesis "The Role of histone modifying enzymes in oesophageal adenocarcinoma: targeting of enhancer of zeste homolog 2 (EZH2)"
No full textDataset to support University of Southampton Doctoral Thesis:
Pickering, O. J. (2025). The Role of histone modifying enzymes in oesophageal adenocarcinoma: targeting of enhancer of zeste homolog 2 (EZH2). [Doctoral Thesis, University of Southampton].
List of differentially expressed genes between OAC cell lines FLO1, MFD-1 and OE33 treated with 5uM tazemetostat, 5uM CPI-1205 or DMSO control for 6 days</span
The Role of histone modifying enzymes in oesophageal adenocarcinoma: targeting of enhancer of zeste homolog 2 (EZH2)
No full textOesophageal adenocarcinoma (OAC) is a cancer of unmet clinical need, with 5-year survival rates <20%. Owing to the high prevalence of loss of function mutations in the SWI/SNF chromatin remodelling subunit ARID1A, OAC tumours have a hypothesised sensitivity to inhibitors of the histone lysine methyltransferase EZH2 (EZH2i), based on observations from other ARID1A mutant cancers. This has not previously been explored in OAC.Initially, through a bioinformatic analysis of a large OAC mRNA dataset (TCGA), high EZH2 mRNA expression was found to be independently associated with worse overall survival (OS). These findings were then validated using immunohistochemistry of a clinically annotated OAC tissue microarray series stained for EZH2 and associated histone 3 lysine 27 trimethylation mark (H3K27me3) which demonstrated EZH2 overexpression in OAC samples, but this was not prognostically significant.The efficacy of EZH2i in OAC was then investigated using a panel of EZH2is alone or in combination with standard of care chemotherapies in cultured OAC cell lines and an EZH2i-sensitive synovial sarcoma cell line. EZH2i showed similar efficacy across all the cell lines and demonstrated a synergistic relationship with 5-FU/ docetaxel in one OAC cell line. Following generation of an ARID1A CRISPR knockout (KO) OAC cell line, EZH2i efficacy was shown to be reduced in the KO cell line compared to wild-type. In addition, ARID1A KO appeared to promote epithelial-mesenchymal transition of the OAC cells, with a morphological change to a more mesenchymal phenotype and associated upregulation of mesenchymal markers determined via western blot and immunofluorescence.Finally, differential gene expression analysis followed by gene set enrichment analysis of mRNA sequencing data from EZH2i treated OAC cells demonstrated enrichment in gene sets involved in interferon alpha and gamma signalling pathways. There was an increase in OAC cell expression of major histocompatibility complex class I and II molecules determined by flow cytometry. In conclusion, this study demonstrates for the first time the efficacy of EZH2i in OAC in vitro. Further, it shows a role for EZH2i in upregulating MHC class I and II expression, which may have clinical utility in OAC patients to improve response to immunotherapy treatment.<br/
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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