130,409 research outputs found
A proline switch explains kinetic heterogeneity in a coupled folding and binding reaction
No full textThe interactions of intrinsically disordered proteins (IDPs) with their molecular targets are essential for the regulation of many cellular processes. IDPs can perform their functions while disordered, and they may fold to structured conformations on binding. Here we show that the cis/trans isomerization of peptidyl-prolyl bonds can have a pronounced effect on the interactions of IDPs. By single-molecule spectroscopy, we identify a conserved proline residue in NCBD (the nuclear-coactivator binding domain of CBP) whose cis/trans isomerization in the unbound state modulates the association and dissociation rates with its binding partner, ACTR. As a result, NCBD switches on a time scale of tens of seconds between two populations that differ in their affinities to ACTR by about an order of magnitude. Molecular dynamics simulations indicate as a cause reduced packing of the complex for the cis isomer. Peptidyl-prolyl cis/trans isomerization may be an important previously unidentified mechanism for regulating IDP interactions
A Proline Switch Explains Kinetic Heterogeneity in a Coupled Folding and Binding Reaction
No full textSlow Escape from a Helical Misfolded State of the Pore-Forming Toxin Cytolysin A
No full textThe pore-forming toxin cytolysin A (ClyA) is expressed as a large α-helical monomer that, upon interaction with membranes, undergoes a major conformational rearrangement into the protomer conformation, which then assembles into a cytolytic pore. Here, we investigate the folding kinetics of the ClyA monomer with single-molecule Förster resonance energy transfer spectroscopy in combination with microfluidic mixing, stopped-flow circular dichroism experiments, and molecular simulations. The complex folding process occurs over a broad range of time scales, from hundreds of nanoseconds to minutes. The very slow formation of the native state occurs from a rapidly formed and highly collapsed intermediate with large helical content and nonnative topology. Molecular dynamics simulations suggest pronounced non-native interactions as the origin of the slow escape from this deep trap in the free-energy surface, and a variational enhanced path-sampling approach enables a glimpse of the folding process that is supported by the experimental data
MeSH term explosion and author rank improve expert recommendations
No full textInformation overload is an often-cited phenomenon that reduces the productivity, efficiency and efficacy of scientists. One challenge for scientists is to find appropriate collaborators in their research. The literature describes various solutions to the problem of expertise location, but most current approaches do not appear to be very suitable for expert recommendations in biomedical research. In this study, we present the development and initial evaluation of a vector space model-based algorithm to calculate researcher similarity using four inputs: 1) MeSH terms of publications; 2) MeSH terms and author rank; 3) exploded MeSH terms; and 4) exploded MeSH terms and author rank. We developed and evaluated the algorithm using a data set of 17,525 authors and their 22,542 papers. On average, our algorithms correctly predicted 2.5 of the top 5/10 coauthors of individual scientists. Exploded MeSH and author rank outperformed all other algorithms in accuracy, followed closely by MeSH and author rank. Our results show that the accuracy of MeSH term-based matching can be enhanced with other metadata such as author rank
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
Scholarly Communication and Publishing Lunch and Learn Talk #11: The ULS Open Access Author Fee Fund
No full textAt the May 2014 talk, you will learn about the ULS Open Access Author Fee Fund--what it is, why we do it, how it works, and how the program is going so far
Language, Race, and Social Class in Howells's America
No full textNo other American novelist has written so fully about language -- grammar, diction, the place of colloquialism and dialect in literary English, the relation between speech and writing -- as William Dean Howells. The power of language to create social, political, and racial identity was of central concern to Americans in the nineteenth century, and the implications of language in this regard are strikingly revealed in the writings of Howells, the most influential critic and editor of his age. In this first full-scale treatment of Howells as a writer about language, Elsa Nettels offers a historical overview of the social and political implications of language in post-Civil War America. Chapters on controversies about linguistic authority, American versus British English, literary dialect, and language and race relate Howells's ideas at every point to those of his contemporaries -- from writers such as Henry James, Mark Twain, and James Russell Lowell to political figures such as Theodore Roosevelt, Henry Cabot Lodge, and John Hay. The first book to analyze in depth and detail the language of Howells's characters in more than a dozen novels, this path-breaking sociolinguistic approach to Howells's fiction exposes the fundamental contradiction in his realism and in the America he portrayed. By representing the speech that separates standard from nonstandard speakers, Howells's novels -- which champion the democratic ideals of equity and unity -- also demonstrate the power of language to reinforce barriers of race and class in American society. Drawing on unpublished letters of Howells, James, Lowell, and others and on scores of articles in nineteenth-century periodicals, this work of literary criticism and cultural history reaches beyond the work of one writer to address questions of enduring importance to all students of American literature andsociety.Cover -- Title -- Copyright -- Contents -- Preface -- Introduction -- One. Language in Howells's America -- Two. "Good Natural English -- Three. American and British English -- Four. Realism and Dialect -- Five. The Problem of "Negro Dialect" in Literature -- Six. Language, Race, and Nationality in Howells's Fiction -- Seven. Language and Class in the Early Novels -- Eight. Language and Class in Novels of Country and City -- Nine. Language and Complicity in The Minister's Charge -- Ten. Language and Equality in the Late Novels -- Conclusion -- Notes -- Works of William Dean Howells -- Index -- A -- B -- C -- D -- E -- F -- G -- H -- I -- J -- K -- L -- M -- N -- O -- P -- R -- S -- T -- U -- V -- W -- ZNo other American novelist has written so fully about language -- grammar, diction, the place of colloquialism and dialect in literary English, the relation between speech and writing -- as William Dean Howells. The power of language to create social, political, and racial identity was of central concern to Americans in the nineteenth century, and the implications of language in this regard are strikingly revealed in the writings of Howells, the most influential critic and editor of his age. In this first full-scale treatment of Howells as a writer about language, Elsa Nettels offers a historical overview of the social and political implications of language in post-Civil War America. Chapters on controversies about linguistic authority, American versus British English, literary dialect, and language and race relate Howells's ideas at every point to those of his contemporaries -- from writers such as Henry James, Mark Twain, and James Russell Lowell to political figures such as Theodore Roosevelt, Henry Cabot Lodge, and John Hay. The first book to analyze in depth and detail the language of Howells's characters in more than a dozen novels, this path-breaking sociolinguistic approach to Howells's fiction exposes the fundamental contradiction in his realism and in the America he portrayed. By representing the speech that separates standard from nonstandard speakers, Howells's novels -- which champion the democratic ideals of equity and unity -- also demonstrate the power of language to reinforce barriers of race and class in American society. Drawing on unpublished letters of Howells, James, Lowell, and others and on scores of articles in nineteenth-century periodicals, this work of literary criticism and cultural history reaches beyond the work of one writer to address questions of enduring importance to all students of American literature andsociety.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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