1,720,962 research outputs found
Network biology identifies novel apoptosis-related proteins and synergistic drug combinations in breast cancer
Get PDFBreast cancer is a very heterogeneous disease with a poor prognostic outcome, largely due to its resistance to current cancer therapies. The balance between cell proliferation and apoptosis plays a critical role in determining the overall growth or regression of the tumor in response to treatments. Hence, identifying treatments involved in apoptosis resistance is essential in order to find new therapeutic approaches.
The heterogeneity of cancer is rarely due to abnormalities in single genes, but rather reflects the discontinuation of complex intercellular processes. Therefore, a useful way to describe and analyse this heterogeneity is the use of systems biology. This approach is based on the study of the interactions between the elements of a given system with the aim to understand its properties. Particularly, the use of protein-protein interaction networks gives a broader perspective of protein environment without losing the molecular details, providing a deeper understanding of the molecular mechanisms underlying complex pathological processes. Thus, the application of network biology can significantly help the elucidation of novel drug targets and more effective therapies.
Since the molecular mechanisms that relate, for instance, changes in expression of the many passenger genes to breast cancer onset and progression are largely unknown, the first objective of this thesis was to identify the role of certain proteins in breast cancer apoptosis, which function on the disease is unknown.
With this aim, we functionally characterized two breast cancer passenger genes, PSMC3IP and EPSTI1, to analyse their potential apoptotic role in breast cancer. We first explored the existence of direct physical interactions with annotated breast cancer-apoptotic genes, and subsequently, we examined several apoptotic markers to determine the effect of PSMC3IP and EPSTI1 gene expression modulation in two different human breast cancer cell lines. Overall, our results showed that PSMC3IP and EPSTI1 are able to modulate the extrinsic apoptotic pathway in estrogen receptor positive and triple negative breast cancer cell lines, highlighting them as potential therapeutic targets.
Currently approved drug combinations are the result of empirical clinical experience, are not being rationally designed and cover only a small fraction of the potential therapeutic space. Therfore, our second objective was to implement two different network biology approaches in order to predict and validate novel synergistic drug combinations for the treatment of breast cancer, with greater clinical efficacy and reduced side effects.
The first approach was based on the quantification of pathway crosstalk inhibition in therapeutic networks. We applied this measure to a set of antineoplastic (cancer drug combined with breast cancer
drug) and compassive (non-cancer drug combined with breast cancer drug) combinations. We next validate experimentally the most promising drug combinations in several breast cancer cell lines. Finally, we determined whether the cytotoxic effect of the selected drug combinations was due to apoptosis induction or cell cycle arrest promotion. Overall, our findings highlight two different antineoplastic combinations as promising therapeutic strategies for triple negative breast cancer subtype.
The second approach integrated the known human interactome with the basal gene expression measurements in hundreds of cancer cell lines, whose sensitivity to several drugs was previously determined. Subsequently, a weighted score in the protein network was defined in order to predict synergistic drug combinations for breast cancer treatment. Finally, we analysed the inhibitory effect of the most promising combinations in different breast cancer cell lines harbouring molecular alterations in PI3K/AKT pathway. Interestingly, our results revealed significant synergism of the drug combinations when compared to single-compound assays. Thus, suggesting this computational approach as a useful tool for the identification of effective and synergistic combinations for breast cancer treatment
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
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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