1,720,957 research outputs found
Aufklärung der Wirkmechanismen der Gephyronsäure und verwandter Verbindungen, die die eukaryotische Protein Synthese inhibieren
Full text linkProtein biosynthesis is a vital, tightly regulated and a complex process involving a number of factors and enzymes. While the bacterial protein synthesis machinery is well understood due to the availability of various small molecule inhibitors, this is not true for the eukaryotic translation system. It is therefore of great interest to study small molecule translation inhibitors and elucidate their mode of action. This study involves four small molecules which target the eukaryotic translation system, i) gephyronic acid A, ii) des-epoxy tedanolide, iii) myriaporone 3/4, and iv) aetheramide B.
All these compounds inhibit growth of human cancer cell lines like KB-3-1 and A-431 in nanomolar ranges. Their cytotoxicity is attributed to the translation inhibition properties. In vitro and in vivo inhibition assays showed that the four substances inhibited translation with IC50 values in the nanomolar range. Using bicistronic vectors the phase of translation inhibition was assessed. Gephyronic acid A and aetheramide B inhibited the initiation, myriaporone 3/4 the elongation. Des-epoxy tedanolide had targets in both phases. A Drug Affinity Responsive Target Stability (DARTS) approach was used to identify the targets of gephyronic acid and myriaporone 3/4. The results showed that gephyronic acid and myriaporone bind directly to the eukaryotic initiation factor 2 alpha (eIF2α) and the eEF2 (eukaryotic elongation factor 2) kinase, respectively. In both cases they are the first natural compounds identified to target these factors. In silico modelling studies suggested that the important epoxide group of gephyronic acid binds to Tyr 39 and Glu 15. The binding of gephyronic acid to eIF2α probably inhibits eIF2α interaction with the guanidine exchange factor eIF2B required for conversion of eIF2α-GDP to eIF2α-GTP. Using immunofluorescence techniques on treated cells it was shown that des-epoxy tedanolide inhibited translation by inducing the phosphorylation of eIF2α and eEF2. Aetheramide B inhibited translation via dephosphorylation of 4E-BP, i.e. by inhibiting the mTOR pathway.Proteinbiosynthese ist ein zentraler, streng regulierter und komplexer Prozess, der eine Reihe von Faktoren und Enzymen einschließt. Während der bakterielle Proteinsynthese-Mechanismus gut verstanden ist, da verschiedene kleine Moleküle als Translationsinhibitoren zur Verfügung stehen, ist das für das eukaryontische Translationssystem nicht der Fall. Es ist deshalb von großem Interesse, niedermolekulare Translationsinhibitoren zu erforschen und ihre Wirkweise aufzuklären. Diese Studie befasst sich mit vier kleinen Molekülen, die mit dem eukaryontischen Translationssystem interagieren, Gephyronsäure A, Des-epoxy-Tedanolid, Myriaporon 3/4 und Aetheramid B.
Alle diese Verbindungen hemmen das Wachstum von humanen Krebszelllinien wie KB-3-1 und A 431 im nanomolaren Bereich. Ihre Zytotoxizität ist auf die Translations-hemmenden Eigenschaften zurückzuführen. Hemmtests in vitro und in vivo zeigten, dass die vier Substanzen die Translation mit IC50-Werten hemmen, die im nanomolaren Bereich liegen. Die Phase der Translationshemmung konnte mit Hilfe bicistronischer Vektoren bestimmt werden. Danach hemmen Gephyronsäure A und Aetheramid B die Initiation, Myriaporon 3/4 die Elongation. Des-epoxy-Tedanolid hat Zielproteine in beiden Phasen. Mit Hilfe eines Drug Affinity Responsive Target Stability (DARTS) Ansatzes konnten die Zielproteine von Gephyronsäure und Myriaporon 3/4 identifiziert werden. Die Ergebnisse zeigten, dass Gephyronsäure und Myriaporon direkt am eukaryontischen Initiationsfaktor 2 alpha (eIF2α) bzw. an der eEF2(eukaryontischer Elongationsfaktor 2)-Kinase binden. In beiden Fällen sind es die ersten identifizierten Naturstoffe, die mit diesen Faktoren interagieren. Modellierungsstudien in silico legen nahe, dass die Bindungspartner der für die Wirkung wichtigen Epoxidgruppe der Gephyronsäure Tyr 39 and Glu 14 sind. Die Bindung von Gephyronsäure an eIF2α hemmt wahrscheinlich die Interaktion mit dem Guanidin-Austauschfaktor eIF2B, die für die Umwandlung von eIF2α-GDP zu eIF2α-GTP nötig ist. Mit Immunfluoreszenztechniken konnte an behandelten Zellen gezeigt werden, dass Des-epoxy-Tedanolid die Translation dadurch hemmt, dass es eine Phosphorylierung von eIF2α und eEF2 induziert. Aetheramid B wirkt über eine Dephosphorylierung von 4E-BP, d.h. über den mTOR-Signalweg
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
No full textWe 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.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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
- …
