1,720,983 research outputs found
Impact of tumour microenvironmental factors on B-cell signalling, migration and adhesion in chronic lymphocytic leukaemia
No full textA key characteristic of chronic lymphocytic leukaemia (CLL) is the accumulation of malignant Bcells in the patients’ lymph nodes, where the microenvironment promotes CLL cell survival andproliferation, in part via B-cell receptor (BCR) signalling and interleukin-4 (IL-4) signalling. BCR signalling is pivotal for disease progression and development. CLL prognosis is heterogeneous, with patients with unmutated (U-CLL) immunoglobulin heavy chain variable (IGHV) being associated with worse prognosis than those with mutated (M-CLL) IGHV. Recently, BCR kinase inhibitors have revolutionised CLL treatment. Nevertheless, some patients fail to respond, or develop resistance by some known and unknown reasons. IL-4 induced pSTAT6(Y641) (phosphorylated signal transducer and activator of transcription 6) signalling enhances BCR expression and signalling in murine splenic B-cells. Therefore, IL-4 may drive BCR signalling and resistance against BCR kinase inhibitors in CLL. In this thesis, I investigated the hypothesis that IL-4 induced pSTAT6(Y641) signalling promotes functional effects associated with disease pathogenesis.I demonstrated, via immunoblotting, that whilst IL-4 induced JAK/STAT6 signalling is not clearly associated with prognostic factors, the cytokine treatment significantly increased expression of the suppressor of cytokine signalling protein 3 more prominently in U-CLL samples. I conclude that IL4 induced signalling can differentially regulate target proteins between prognostic subsets.Using immunophenotyping, I demonstrated that IL-4 induces sIgM expression on CLL cells, with more prominent effects in the U-CLL subset. Intracellular calcium flux analysis demonstrated that IL-4 enhances anti-IgM induced signalling and immunoblotting showed that IL-4 increases expression of proteins known to promote BCR signalling. The survival factors CD40 ligand and Bcell activating factor had no clear effects on BCR expression or signalling. I also demonstrated that IL-4 can reduce the ability for BCR kinase inhibitors to induce apoptosis and block anti-IgM induced signalling. I propose that co-treating CLL patients with BCR kinase inhibitors in combination with inhibitors, such as JAK3 inhibitors, targeting IL-4 signalling could have therapeutic potential.I further showed, with flow cytometry, that IL-4 reduces chemokine receptor expression and enhances the expression of adhesion molecule CD44 on CLL cells. Adhesion assays showed that IL4 can enhance anti-IgM induced CLL cell adhesion to the extracellular matrix component fibronectin. Collectively, these findings suggest that IL-4 may promote CLL cell localisation and retention in the lymph node.Together these findings mostly support the hypothesis and suggest that IL-4 induced pSTAT6(Y641) signalling may promote CLL pathogenesis in vitro. This thesis advances the field by further suggesting that IL-4 may promote disease pathogenesis and showing how small inhibitors targeting the cytokine signalling could provide a potential therapeutic target for CLL
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Ex-vivo signal transduction studies in chronic lymphocytic leukemia
No full textMicroenvironmental signaling is pivotal to chronic lymphocytic leukemia (CLL) pathology; therefore understanding how to investigate this pathway by both protein and chemical methods is crucial if we are to investigate and correlate biological changes with therapeutic responses in patients. Herein, we describe the use of western blotting also referred to as immunoblotting as a method that can semiquantitatively evaluate changes in protein expression following receptor engagement; this includes B cell receptor (BCR) signaling following stimulation with anti-IgM (Blunt et al. Clin Cancer Res 23(9):2313–2324, 2017). It is important to note that immunoblotting should always be combined with other quantitative methods such as flow cytometry to confirm activation of these signaling pathways (Aguilar-Hernandez et al. Blood 127(24):3015–3025, 2016).</p
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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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