1,720,953 research outputs found
Effect of Osmolytes on the Interplay of Water Protein and DNA in EcoRI DNA Recognition using Molecular Dynamics Simulations
EcoRI is a type II restriction endonuclease that has been widely used as a model system to study protein-DNA interaction owing to its high degree of specificity. This enzyme does not recognize even a single basepair change in its recognition sequence, (GAATTC)2, under normal conditions. However, in the presence of osmolytes, such as glycerol and DMSO, the specificity of EcoRI is slightly relaxed and recognizes sequences that differ from its cognate sequence in the first basepair position. This relaxed specificity has been attributed to the dehydration of the EcoRI-DNA which presumably results in tighter complex formation and subsequent catalysis. However, it may be noted this is insufficient to explain the lack of recognition of DNA sequences that differ at second position or sequences that differ by more than one basepair.
In this thesis, we hypothesized that the relaxation in specificity is not only because of the dehydration of the EcoRI-DNA interface, but also because of its combined effect on the free EcoRI, free DNA and the EcoRI-DNA complex. To investigate this, we performed molecular dynamics simulations of free EcoRI, free DNA and the protein-DNA complex in the presence and absence of different concentrations of two osmolytes, viz., glycerol and DMSO. We used noncognate DNA sequences that differ from the cognate sequence in the first basepair (CAATTC, AAATTC and TAATTC) and as well used a non-specific sequence (TAGCTA) in our study. Our results show the following: (i) In free DNA, there is a sequence-dependent dehydration of the DNA sequence. This is also associated with a transition of the DNA conformation from the BI to BII state which may facilitate the binding of EcoRI.
Further, we observed that while glycerol interacts with DNA directly, DMSO does not as much as glycerol indicating that the two osmolytes may be exerting their action through different modes. Further analyses show that DMSO probably facilitates protein binding by the entropic advantage of the release of water, whereas Glycerol may facilitate protein binding through an entropically favourable displacement of glycerol, contributing to a net decrease in the free energy of binding (ΔG). (ii) The essential dynamics of the free EcoRI is altered in the presence of osmolytes to that similar to that when bound to cognate DNA.
Further, osmolytes slow down the tumbling motion of the interfacial waters, which, in turn, slows down the break-and-make of hydrogen bonds of the interfacial waters with functionally important residues. These results point to the idea that osmolytes may poise the EcoRI for binding to DNA sequences. (iii) In EcoRI-DNA complex systems, our results shows that the osmolyte-induced dehydration of the protein-DNA interface is associated with a number of attendant changes including retarded water dynamics, restored DNA kinking, partially restored protein-DNA hydrogen bonds and altered conformational landscape of EcoRI.
These attendant changes possibly help in relaxing the protein-DNA specificity. The gamut of changes in the structure and dynamics of the biomolecules in the presence of osmolytes not only shows the complex interplay underlying in the osmolyte-EcoRI-DNA-water systems, but also provides a framework to understand the extent of relaxation of protein-DNA specificity in the presence of osmolytes in general. In other words, this thesis contributes the literature on EcoRI-DNA specificity as well as points out to the need to dissect and understand the complex interplay that underlies biomolecular recognition in the presence of other cosolutes such as osmolytes
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
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-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
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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