1,720,964 research outputs found
Computational frameworks to aid pharmacological studies : Tools, Databases and Prediction models
No full textRational approaches to the traditional drug discovery process rely on high-throughput and lowthroughput bioactivity or phenotypic screening studies. Such profiling strategies have been the foremost step utilized when identifying or curating lead molecules, and more recently, when evaluating compound repositioning/repurposing opportunities. Although promising, such systematic approaches are inherently limited by their cost and labor constraints, and the necessity of specific screening equipment’s renders them outside the scope of many academic laboratories. Further, elucidation of any novel associations through such experimental techniques require exhaustive searches of compound libraries. Hence, many positive drug indications revealed, though rational, are often by the virtue of serendipity.
The accumulation and standardization of existing compound profiling datasets has paved the way to the field of chemoinformatics. Wherein, data-driven computational approaches are employed as a pragmatic solution to challenge the inherent notion of serendipity in screening studies. Such in silico models serve as an efficient and cost-effective augmentation to the experimental screening approaches, circumventing the intrinsic limitations of current drug discovery methods. This study therefore was motivated towards identifying niches and limitations prevalent in the current pharmacological paradigm, where an effective computational framework could be utilized to complement and expedite the conventional drug discovery process. The various computational approaches proposed in this article-based thesis include exploratory web-tools, new data resources, and prediction models, that are introduced as supplements to extend the current computer-aided drug discovery process (CADD).
Firstly, I developed a web-application, termed C-SPADE, a novel compound-centric chemoinformatic tool that facilitates interactive analysis and visualization of compound screening experiments using Compound-SPecific bioActivity DEndrograms. The tool employs compound-compound similarity metrics to estimate the diversity amidst compounds profiled in the screening panel and intuitively represents the chemical similarity space and the observed bioactivity values. The web-tool provides users an exploratory framework to perform pharmacological analysis and investigate novel compound associations employing diverse compound similarity clusters. Secondly, to address the heterogeneous and non-standardized bioactivity data in existing data resources, a comprehensive open-data platform, called Drug Target Commons (DTC), was developed. DTC feature tools for data annotation, standardization, curation to address intra-resource heterogeneity and provide users a one-stop resource for drug discovery and in silico model development endeavours. User-specific applications of both the above-mentioned resources have been demonstrated through several case studies and experimental validations.
In addition to the tools and databases, I have also designed and implemented diverse machine learning models primarily to predict potent compound-kinase interactions and to fill the current experimental gaps in large-scale activity profiling studies. Firstly, through collaborative efforts, we employed the Kronecker kernel-based regularized least square regression (KronRLS) algorithm under different crossvalidation settings to predict both the uncharacterised binding measures in large-scale profiling studies and novel compound-target associations. As a case study, the off-target profile of an investigational VEGF receptor inhibitor tivozanib was predicted and experimentally validated. Secondly, I designed and implemented an efficient statistical model utilizing an ensemble SVM classifier to prioritize potent compound-kinase association for biochemical testing. The developed computational framework was termed Virtual Kinome Profiler (VKP) and was efficiently used in compound repositioning and lead identification studies, wherein 19 novel kinase-compound interactions spanning across different kinases were predicted and experimentally validated. Apart from elucidating the chemogenomic similarities prevalent among distinct kinase proteins, VKP with a positive prediction value (PPV) of 84% was shown to reduce the time and cost constraints related to traditional experimental screening process.
Most of the computational frameworks proposed in this thesis are designed and deployed with an accompanying web-based graphic user interface (GUI). This in turn aids in the translatability of the platforms, overcoming the current prerequisites required when utilizing CADD models, including prior expertise in data analysis and scripting languages. These studies together exemplify new applications of computational models in diverse areas of the drug discovery process, subsequently making invaluable augmentations to a chemical biologist’s toolbox.ei saavutettav
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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