1,720,956 research outputs found
Design and Application of Novel Ligand-Dependent RNA Catalysts Toward Regulating Gene Expression
No full textRNA is a highly versatile molecule that is involved in numerous aspects of gene expression including protein synthesis, RNA maturation, RNA editing, RNA turnover, translational regulation, and protein trafficking. A seminal discovery that significantly diversified the functional repertoire of RNA came in the early 1980s with the Nobel Prize-winning discovery that certain RNAs possess catalytic activity. RNA catalysts (ribozymes) abound in nature, possess a wide range of activities, and are involved in several aspects of gene expression. The multifunctional character of RNA has propelled the development of novel RNA- based therapeutic and diagnostic agents. Although ribozymes are highly versatile in such applications, their activities are not naturally subject to regulatory mechanisms. The ability to control ribozyme activity would be beneficial toward regulating the processes in which they are involved. Therefore, I am interested in engineering RNA catalysts that can be artificially regulated by the binding of specific ligands. Such allosteric ribozymes might serve as controllable molecular switches in both therapeutic and diagnostic applications. Toward the goal of developing ligand-dependent RNA catalysts and assessing their intracellular function, I have isolated and characterized a variety of allosteric ribozymes derived from the hammerhead and Hepatitis Delta Virus (HDV) ribozymes, as well as Tetrahymena group I self-splicing intron. The generation of allosteric ribozymes is achieved by functionally integrating ribozyme and ligand-binding RNA domains using rational design strategy and combinatorial selection techniques.
Through combinatorial selection of allosteric HDV ribozymes, a small RNA module was isolated that functions as a conditionally folded element capable of adjoining a variety of ligand-binding and ribozyme domains. The module not only provided an opportunity to examine the structure-function relationship between ligand binding and catalysis, but also enabled the generation of novel allosteric ribozymes. Using rational design, the module facilitated construction of allosteric Tetrahymena group I self-splicing introns. Certain allosteric self-splicing introns were demonstrated to function intracellularly, where one was further capable of regulating reporter gene expression in E. coli. Toward the goal of utilizing allosteric ribozymes to modulate mammalian gene expression, I explored whether ligand-dependent HDV ribozymes could regulate the production of small interfering RNAs (siRNAs) that function through the RNA interference (RNAi) pathway to down-regulate target gene expression. Although the allosteric ribozymes failed to regulate target gene expression, constitutively active or inactive ribozyme constructs demonstrated that ribozyme-mediated siRNA production and RNAi are fundamentally achievable. Taken together these studies demonstrate that the modular character of functional RNAs can be exploited to generate ligand-dependent ribozymes. Moreover, such catalysts are capable of functioning intracellularly in response to ligand, and can be utilized to regulate gene expression.ProQuest Traditional Publishing Optionvi, 157 page
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
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