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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
The structural and functional characterization of the extracellular domain of vascular endothelial growth factor receptors : their role in receptor activation and use as therapeutic targets
Get PDFAbstract: The vascular endothelial growth factor (VEGF) family plays key roles in the development of the blood and lymphatic vasculature. Five members, VEGF A, B, -C, -D, and PlGF can be found in the human body. They bind in an overlapping pattern to three receptor tyrosine kinases (RTKs), which constitute the type V family of RTKs: VEGF-receptor (VEGFR)-1 (also known as Flt1), VEGFR-2 (KDR/Flk1), and VEGFR-3 (Flt4). While VEGFR-1 and VEGFR-2 are mainly involved in angiogenesis, VEGFR-3 is the key player in lymphangiogenesis. VEGFRs consist of seven immunoglobulin-homology domains constituting the extracellular domain (ECD), a single transmembrane helix, and a split tyrosine kinase domain. Ligand binding to the VEGFR ectodomain initiates receptor dimerization, followed by kinase activation and autophosphorylation. Phosphorylated tyrosine residues in the intracellular domain of VEGFRs act as docking sites for a number of different signaling molecules.
In addition to physiological angiogenesis, aberrant VEGFR signaling is associated with a variety of pathological conditions such as in cancer, in ischemic, and in inflammatory disorders. Several inhibitors of VEGF-signaling have been developed most of which are at different stages in clinical trials. However, anti-angiogenic treatment of cancer is often accompanied by severe side-effects and tumor patients tend to develop resistance to the treatment. Hence, structural studies of the VEGF receptor system may further elucidate the molecular mechanism underlying receptor activation and thereby help to develop new more specific drugs complementing existing therapies.
During this project, I showed that binding of individual VEGFR-1 ligands resulted in conformationally similar ligand/VEGFR-1 ECD complexes. Besides showing ligand induced dimerization, the complexes reveal homotypic receptor/receptor interactions in the membrane proximal Ig homology domains. Our study is also the first addressing the thermodynamic contributions of individual Ig homology domains of VEGFR-1 to ligand binding. I showed that VEGFR-1 D4-7 positively contribute to ligand binding as shown by the higher affinities of the ligands for VEGFR-1 D1-7 compared to binding to the minimal ligand binding domain D1-3. Surprisingly, I discovered that Ig homology domain 1 blocks PlGF-1 binding to VEGFR-1 D1-3 but not to D1-7. The exact mechanism explaining this phenomenon remains unclear.
In a second project, we showed that Ig-homology domains 4 and 7 are indispensable for VEGFR-2 activation. The loop connecting β-strand E and F in Ig-homology domain 7 represents the element that are required for receptor activation by mediating contacts with Ig-homology domain 7 of the second receptor chain in the dimerized complex. We generated Designed Ankyrin Repeat Proteins (DARPins) that specifically target the low affinity receptor/receptor interactions formed upon ligand binding and identified a DARPin binding to Ig-homology domain 4 that blocks VEGFR-2 activation and phosphorylation without preventing the formation of the VEGF A/VEGFR-2 complex. This inhibitor also affected downstream signaling and inhibited sprout formation of endothelial cell spheroids. This type of inhibition displays a new inhibition mechanism for VEGFR-2 that might be applied complementarily to other therapeutic approaches to improve the efficiency of anti-angiogenic therapy. ---------- Zusammenfassung:
Die Familie der VEGFs spielt eine wichtige Rolle in der Entwicklung des Blut- und Lymphgefässsystems. Im menschlichen Körper sind fünf Mitglieder, VEGF A, -B, -C, -D, und PlGF anzutreffen. Sie binden in einem überlappendem Muster zu drei Rezeptor Tyrosin Kinasen, die die Typ V Familie der RTKs bilden: VEGFR-1 (auch bekannt als Flt1), VEGFR-2 (Flk1), und VEGFR-3 (Flt4). Während VEGFR-1 und VEGFR-2 hauptsächlich in der Angiogenese involviert sind, stellt VEGFR-3 eine Schlüsselfigur in der Lymphangiogenese dar. VEGFRen bestehen aus 7 Immunoglobulin-ähnlichen Dömanen in der extrazellulären Domäne, einer einzelnen membrandurchziehenden Helix, und eine geteilten intrazellulären Kinasedomäne. Ligandenbindung an die extrazelluläre Domäne initiiert Rezeptordimerisierung, gefolgt von Kinasenaktivierung und Autophosphorylierung. Phosphorylierte Tyrosinseitenketten in der intrazellulären Domäne von VEGFRen agieren als Bindestellen für eine Vielzahl von Signalmolekülen.
Neben der physiologischen Angiogenese sind VEGFR-Signalwege auch in einer Vielzahl von pathologischen Konditionen involviert, z.B. Krebs, ischämischen und Entzündungskrankheiten. Eine Reihe an Inhibitoren wurde entwickelt, von denen die meisten sich in verschiedenen Stadien von klinischen Studien befinden. Allerdings wird die Anti-Angiogenese Behandlung von Krebs oft von starken Nebenwirkungen begleitet und Krebspatienten neigen dazu eine Resistenz gegen die Behandlung zu entwickeln. Daher könnten strukturelle Studien dieses Rezeptorsystems weiter dazu beitragen den molekularen Mechanismus, der der Rezeptoraktivierung unterliegt, aufzuklären, als auch helfen neue Medikamente zu entwickeln die benötigt werden um bestehende Therapien zu erweitern.
Während dieses Projektes, habe ich gezeigt, dass die Bindung der einzelnen VEGFR-1 Liganden in ähnlichen Liganden/VEGFR-1 ECD Konformationen resultierte. Die Komplexe sind neben der Dimerisierung durch den Liganden durch weitere homotypische Rezeptor/Rezeptor Interaktionen in den membrannahen Ig-homologen Domänen geprägt. Ausserdem, ist dies die erste Studie, die die thermodynamische Beteiligung individueller Ig-homologie Domänen zum Prozess der Ligandenbindung behandelt. Dabei habe ich gezeigt, dass VEGFR-1 Domäne 4-7 eine positive Beteiligung am Prozess der Ligandenbindung besitzt, was durch niedrigere Affinitäten der Liganden für VEGFR-1 D1-7 im Vergleich zur minimalen Ligandenbinde Domäne gezeigt wurde. Überraschenderweise, habe ich entdeckt dass Ig-homologie Domäne 1 die PlGF-1 Bindung an VEGFR-1 D1-3 aber nicht die Bindung an D1-7 behindert. Der genaue Mechanismus, der dieses Verhalten erklären würde, ist jedoch unklar.
In einem zweiten Projekt, zeigen wir dass Ig-homologie Domäne 4 und 7 unersetzlich für die VEGFR-2 Aktivierung sind. Innerhalb der Ig-homologie Domäne 7 ist es der Loop, der β-Strang E und F verbindet, der die wichtigen Elemente für die Rezeptoraktivierung beinhaltet. Dieser Loop interagiert mit demselben Loop in der Ig-homologie Domäne 7 der zweiten Rezeptorkette im dimerisierten Komplex. Daher haben wir DARPins generiert die spezifisch die niedrigaffinen Rezeptor/Rezeptor-Interaktionen anzielen, die sich durch die Ligandenbindung bilden. Wir beschreiben einen DARPin, der Ig-homologie Domäne 4 bindet und der zu einer verringerten VEGFR-2 Phosphorylierung führt ohne dabei die Ligandenbindung zu stören. Dieser Inhibitor wirkt sich auch auf Abwärtssignalwege zu PLCγ1 aus und inhibiert die Bildung von neuen Trieben von Endothelzellen. Diese Art von Inhibition stellt einen neuen Inhibitionsmechanismus für VEGFR-2 dar, der komplementär zu anderen Behandlungen benutzt werden kann um die Effizienz der Anti-Angiogenese Therapie zu verbessern
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
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
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