1,720,953 research outputs found
Investigating Synergistic Effects of PRMT5 Inhibitors Paired with BH3 Mimetics in Double-Hit Lymphoma
Full text linkDouble Hit lymphoma (DHL) is an aggressive B cell malignancy and comprises 6% of diagnoses among lymphoma cases which is estimated to reach ~2000 cases annually in the US. It primarily affects adult males in their late fifties and sixties and poses unique clinical challenges as it lacks a definitive standard of care. DHL has a poor prognosis with an overall survival ranging from 22%-43% over the span of 1.4-5.0 years. An initial response to standard chemotherapy is commonly observed, but relapse is inevitable, and to date there is no cure. DHL has a poor prognosis due to the aggressive nature of the disease and older patient demographic, which can limit their options for intensive treatment regimens. The lack of effective treatment options and inevitable fatality of a DHL diagnosis emphasize the paramount need for novel therapeutic strategies for DHL.
Our group, Baiocchi Lab, was the first to identify the overexpression of Protein Arginine Methyltransferase 5 (PRMT5) as a key driver of DHL pathogenesis. PRMT5 is an enzyme that catalyzes the methylation of arginine residues on histones and many key proteins for cell cycle progression and survival. This post-translational modification results in the silencing of tumor suppressor genes which contributes to cell transformation and cancer. In our work to explore the effects of PRMT5 inhibition and its potential to reprogram DHL cells, we have discovered that combining PRMT5 inhibition with Bcl-2 inhibition results in synergistic cell death. BCL-2 family proteins can be broadly categorized as pro- or anti-apoptotic and their relative abundances and binding interactions determine if a cell will live or die. The synergy observed between PRMT5 inhibition and Bcl-2 inhibition in other DHL cell lines made us curious about what other effects PRMT5 causes and what is the underlying reasoning for this synergy. We hypothesized that PRMT5 inhibition lowers the apoptotic threshold in DHL by modulating levels of BH3 family proteins to favor a pro-apoptotic state. Major experiments done to unfold our hypothesis were: MTS assay, which visualized our combined treatment results to see if synergy was present; Western blotting, to probe for what mechanisms were causing the synergy; and Immunofluorescence Microscopy, which allowed us to visualize changes in FOXO1 localization in DHL cell lines upon PRMT5 inhibition. Further investigation led us to believe that this upregulation in expression is because, in DHL, PRMT5 is inhibiting FOXO1 localization into the nucleus where it serves as a transcriptional factor for BH3-domain proteins. MTS assays showed that combined treatment induced synergy, especially in dosage concentrations high in PRT808 and low in Venetoclax. Western blotting revealed significant changes in abundance of pro-apoptosis proteins and BCL-2 family proteins with PRMT5 inhibition. IF confirmed upon PRMT5 inhibition via PRT808 treatment, FOXO1 is capable of localizing into the nucleus at greater quantities.
In summary, we have successfully unveiled key characteristics of DHL and began the groundwork on the journey to create a specific, effective, and targeted therapy for DHL. Let alone amongst all DHL lines, within DHL cell lines that share a differentiation state, ABC or GBC, there are profound differences in their responses to treatments and phenotypes. This further emphasizes the importance of characterizing DHL to have a greater understanding of how we can target it effectively on a case-by-case basis.Undergraduate Research ScholarshipNIH MARC T34No embargoAcademic Major: Molecular Genetic
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
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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