1,721,050 research outputs found
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
STRUCTURAL INSIGHTS INTO THE INTERACTION BETWEEN THE TANDEM PHD FINGER DOMAIN P5C5 OF NSD1 AND THE ZINC FINGER MOTIF C2HR OF NIZP1.
Point Mutations or translocation in NSD1 cause the overgrowth disorder Sotos syndrome and acute myeloid leukemia (AML), respectively (Berdasco M. et al, 2009, Wang G et al, 2003). NSD1 contains several chromatin related domains including a SET domain responsible for histone methyltranferases activity (H3K36 and H4K20), two nuclear receptor-interaction (NID) motifs, five zinc finger domains (PHD1-5), a variant PHD finger (C5HCH), two proline-tryptophan-proline-tryptophan (PWWP1-2) domains (Lucio-Eterovic AK, et al , 2011), suggesting a role in chromatin regulation and gene expression. 20 pathological Sotos mutations have been detected on the PHD tandem domain composed by NSD1-PHD5 and NSD1-C5HCH (NSD1-P5C5). The tandem domain is essential for the pathogenesis of acute myeloid leukaemia (AML) caused by the chimeric protein NUP98/NSD1 that forces the abnormal activation of Hox-A and Meis1 genes (Wang at al 2007). The deletion of this tandem domain is sufficient to abolish NUP98/NSD1 interaction with chromatin, preventing both the transcription activation of HOX genes and the immortalization of myeloid progenitors. The biological role of NSD1-P5C5 is still unclear. It was proposed that this tandem domain is involved in the recognition of both H3K4me3 and H3K9me3 histone marks, (Pasillas M et al. 2011). However, biophysical experiments in our laboratory did not confirm these results challenging the idea that this tandem domain can really work as epigenetic reader. Previous biochemical studies suggested that NSD1-P5C5 can also work as protein-protein interaction motif, being able to bind to the co-repressor Nizp1 by its C2HR zinc fingers motif (Nizp1-C2HR) thus mediating gene repression (Nielsen AL et al, 2004).
The structural determinants of this interaction are still unknown and have been object of this thesis. In order to get more insights into the physiological and pathological role of NSD1-P5C5, we have solved its (i) solution structure by NMR spectroscopy and (ii) characterized its interaction with Nizp1-C2HR.
NSD1-P5C5 folds as unique functional unit adopting a “face to side orientation”. In particular NSD1-PHD5 (or NSD1-P5) presents the canonical PHD finger fold, whereas the NSD1-C5HCH (or NSD1-C5) domain displays an atypical topology characterized by the presence of an additional two stranded β-sheet. In order to investigate the impact of Sotos point mutation on NSD1-P5C5 we expressed and purified seven mutants and analyzed them by NMR. The majority of them destabilize the fold, with the exception of the solvent exposed mutation Arg2152Gln and His2205Arg suggesting a functional role for these residues.
We next solved the solution structure of the zinc finger Nizp1-C2HR, an atypical Cys2His2-type zinc finger in which the fourth zinc chelating residue is substituted by an arginine residue. Its fold consists of a short α-helix and of a short two-stranded β-sheet hold together by one zinc ion. Importantly, we showed that three zinc ligands are sufficient to maintain the protein domain fold and functionality.
NMR titrations of 15N labelled NSD1-P5C5 with Nizp1-C2HR and 15N labelled Nizp1-C2HR with NSD1-P5C5 clearly show that the two proteins directly interact. Analysis of the chemical shift displacements upon complex formation allowed to identify the residues of the two protein domains involved in protein-protein interaction. The interaction surface is located on the interface between NSD1-P5 and NSD1-C5 and on the α-helix of Nizp1-C2HR, respectively.
Based on this information using the software HADDOCK we have computed a data driven docking model of the protein complex. In the model Nizp1-C2HR places its α-helix in the groove at the interface between NSD1-P5 and NSD1-C5, creating both hydrophobic and polar intermolecular contacts.
The thermodynamic parameters that govern complex formation were studied by ITC titrations: the binding reaction is entropy-driven, with a stoichiometry of 1:1 and a Kd of 3,80±0,66 μM. In order to solve the structure of the protein complex we performed crystallographic screenings, and we have found preliminary conditions for obtaining single crystals.
In conclusion, the presented results provide novel information on the interaction between a tandem PHD finger domain and zinc finger motif. The results represent, to the best of our knowledge, the first biophysical characterization between two zinc binding domains. Most importantly, these data give the first molecular details of the interaction between NSD1 and Nizp1 and may provide useful insights into the function of NSD1 and its role in pathological conditions both in Sotos Syndrome and AML. Future work will be dedicated to the full three-dimensional characterization of the complex and to the analysis of Sotos mutations on complex formation
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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