1,720,956 research outputs found
Targeting the splice factor kinases SRPK1 and CLK1 in leukaemia
Get PDFThis study was aimed at investigating the effect of inhibiting SRPK1 in leukaemic cells. It was also aimed at exploring the potential utility of combining conventional leukaemia chemotherapy (such as imatinib) with compounds that inhibit SRPK1.SRPK1 is best known for its role in the phosphorylation of serine/argenine rich proteins (SR-proteins) which are responsible for constitutive and alternative mRNA splicing. Studies have associated elevated levels of SRPK1 with tumour growth, proliferation and invasiveness with inhibition resulting in decreased tumour growth and altering the choice of alternative splice site. Imatinib mesylate and azacytidine remain the drugs of choice for the management of chronic myeloid leukaemia (CML) and acute myelogenous leukaemia (AML) respectively. Studies have shown that both imatinib and azacytidine are able to reduce the growth of proliferating Bcr/Abl+ and AML cells principally through the induction of apoptotic cell death.SRPK1 was inhibited using the small molecule inhibitor SPHINX. SPHINX was combined with either imatinib in a CML cell line (K562) or azacytidine in an AML cell line (Kasumi-1) for up to 72hrs. Results suggest that the SPHINX compound affects the ability of SRPK1 to phosphorylate its substrates in all three cell lines (TK6, K562 and Kasumi-1). Inhibition of SRPK1 was found to reduce cell viability in Kasumi-1 cells and at higher concentration, affect K562 cell viability consistent with the work of Sanidas et al.,(2010). There was also an indication that SRPK1 could be regulating its own expression through a feedback loop in a cell line-dependent manner.Studies with imatinib mesylate and azacytidine showed that both imatinib mesylate and azacytidine are able to reduce cell growth and viability in a dose and time-dependent manner. On combining them with SPHINX, a combination of azacytidine and SPHINX had an additive effective on Kasumi-1 cells but not with imatinib mesylate in K562 cells. Results also showed that imatinib affected the alternative splicing of caspase 9 favouring a pro-apoptotic isoform, caspase 9a. Imatinib mesylate alone also caused an apparent reduction in the expression of SRPK1, CLK1 and SRSF1, suggesting that pathways imatinib affects cell signalling pathways that regulate the expression of these oncogenic splice factor kinases and splice factors. In summary, this thesis presents evidence that targeting SRPK1 could potentially provide therapeutic benefit in the treatment of a range of leukaemias; further research is now needed to explore this novel approach
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
Organ wide toxicological assessment of common edible herbs and their mixtures as used in home remedies
Get PDFThe use of home remedies for medicinal purposes, most of which are edible plants has continued to be a practice in many homes. However, there has been an increasing report of chronic use with lethal effect. Among the commonly used herbal/ medicinal plants were ginger, garlic and lemon. These were seen to be prevalent across continents with brewing and crude extraction being the most means of consumption. This study investigated the organ wide toxicity of this extract following chronic consumption of crude extract. Twenty-five albino Wister rats, five in each group were used for this experiment. Each animal received 0.5ml/kg body weight of either ginger extract, garlic extract, lemon juice, or a mixture of equal volumes of all three extract (v/v) respectively twice daily for seven (7) days. Statistics were represented as ±SE; P≤0.05 was considered significant. Previous studies have shown that moderate consumption of these medicinal plants were beneficial and have shown no deleterious effect. This study observed no change in the weight of the experimental animals. The weight of the animals continued to increase except for the group that received lemon and the mixture, but these were not significant. It was observed that chronic consumption induced organ wide toxicity to include the liver, kidney, intestinal epithelium, stomach, and pancreas. These were shown to alter tissue architecture and the cell morphology. Packed cell volume was reduced in the lemon and the group that received a combination of all extracts (p=o.03). Blood differentials showed changes in levels. An elevated basophil level was observed in ginger and garlic (p<0.0001; p=0.0006). Monocyte levels increased progressively across each group when compared to the control with the most elevated level seen in the group that received the mixture (p<0.0001). Lymphocyte count was reduced across all the groups that received the extract except for animals that received ginger. This study suggests the application of caution among users of these medicinal plants and continues to draw attention to the need for harmonization and standardization of safe use doses.N/
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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