1,721,066 research outputs found

    Statistical physics approach to gene regulatory networks

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    Gene expression is a complex process that should be regulated in each cell of every organism in order to ensure the proper functioning throughout its life. It is unavoidably subject to several sources of noise, due to the low copy number of molecules or to their diffusive motion inside the cell, that impose physical limits to the reliability of regulation. The regulation is generally performed by networks of molecules (proteins or RNAs) that interact with each other, often defined as gene regulatory networks (GRNs). In this thesis we adopt a statistical physics approach to study the regulation of gene expression at several levels, in different biological contexts. We start with a theoretical treatment about the limits of information flow in simple regulatory networks in which one controller regulates the levels of multiple targets. We consider network parameters as quenched random variables and, using tools from statistical field theory, we characterize the average of the maximum mutual information and its probability distribution induced by this randomness. The relevance of this study lies in the development of an analytical approach to ensembles of simple GRNs and it shows, among other things, that the optimization of network parameters could be less significant than the optimization of the input variable (i.e., the concentration of the controller). This conclusion is made stronger in large networks, where kinetic heterogeneities can be exploited for a reliable information transmission. Since the experimental quantification of gene expression is essential for the detailed study of regulatory processes, afterwards we leave the purely theoretical approach in favor of a data-driven one. Specifically, we extend to single-cell RNA-sequencing (scRNA-seq) data an information theoretic framework that characterizes the information content of samples of complex systems. We use it to evaluate different cells’ clusterings of a scRNA-seq dataset and we show how it can be exploited to identify maximally informative partitions of data. Afterwards, we study the influence of cell-to-cell variability of gene expression (partly caused by its stochastic nature) in the pathogenesis of multiple sclerosis. We work on scRNA-seq data of monozygotic twins discordant for the disease. Working on single-cell data allows to study the variability of gene expression across cells of the same type (in our case B cells), while the monozygotic twins allow to evidence the non-genetic factors which putatively cause the disease. Relying again on the framework mentioned above, we extract lists of “critical genes” from the dataset, for each subject. We refine the method exploiting previously identified markers of the disease, obtaining also lists of critical genes that are linked to them. These results are then crossed with differential expression and differential noise analyses, leading to a list of candidate genes likely linked to multiple sclerosis, which is actually under experimental validation. Finally, the last part of the thesis regards the mathematical modeling of a RNA network based on microRNAs that controls the early stage of myogenesis. Our goal is to analyze the regulatory role played by the two microRNA biosynthesis modes, one controlled by a miRNA-decoy system, the other consisting in its production from an independent genomic locus, and that played by the presence of competition between coding and non coding RNAs to bind microRNAs. We show that the miRNA-decoy system is sufficient to tune molecular levels at steady state, while the alternative locus for miRNA transcription serves a dynamical purpose, allowing the quick concentration shifts required by the differentiation process. This study suggests that these joint regulatory mechanisms could be a common feature of other biological processes

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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 Under Sail The Imagination of Jack London, 1893-1902

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    In 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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