1,720,963 research outputs found
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
Variations on the Author
No full text“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
No full textWe 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
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
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
The Power of Fragments FBLD approach to investigate protein structures
No full textFragments are small chemical entities with the extraordinary advantage of belonging to a wide variety of functional groups able to explore various chemical spaces, penetrate small protein pockets and allow the mapping of various protein binding sites. Nowadays, fragment-based lead discovery (FBLD) is the method of choice to screen fragment libraries and plays an increasingly important role in the drug development process. It becomes therefore particularly important to have a general-purpose fragment library ready to use. In our group a 96-fragment library was validated on eight protein targets, which was designed in a joint project between the HZB MX-group at BESSY II (AG Weiss) and the Institute of Pharmaceutical Chemistry, University of Marburg (AG Klebe) (Part I). Among the eight validated proteins, there are Thermolysin (TLN, Part II) and Trypanosoma cruzi Farnesyl Pyrophosphate Synthase (T. cruzi FPPS, Part III) which were the main focus of the present study. The 96-fragment library was therefore used as primary X-ray crystallographic screening method to search for novel chemical scaffolds. However, a new soaking protocol had to be established prior to the fragment screening. In fact, unlike the typical TLN inhibitor, fragments usually have insufficient affinity to displace on their own the autoproteolitically product Val-Lys dipeptide which occupies the TLN active site. The protein crystals were therefore incubated in an isopropanol solution able to displace the dipeptide and subsequentially screened against the fragment library resulting in seven crystallographic fragment hits. Unlike TLN which is usually used as a model protein, T. cruzi FPPS is a key enzyme involved in the mevalonate pathway and is essential for sterol production. T. cruzi and T. brucei parasites cause Chagas disease (CD) and human African trypanosomiasis (HAT) respectively and inhibition of FPPS in these species is therefore a valid target to fight these two tropical diseases. The present work focused first on optimizing the stability of protein samples in solution using various techniques such as thermal shift assay (TSA) and light scattering (LS). A crystallization and soaking protocol were subsequently established prior to performing a crystallographic fragment screening of the above-mentioned 96 fragment library. In addition, the role of the magnesium ion as cofactor of the enzyme was also elucidated, either alone or in complex with isopentenyl pyrophosphate (IPP) or bisphosphonates (BPs). Based on the discovery by Jahnke et al. of a new allosteric pocket in human FPPS, it was assumed that a similar pocket was also present in the Trypanosoma species which was therefore the main target-site of the present work. The fragment screening project resulted in three crystallographic hits, one of which binding the allosteric pocket while the other two in a new pocket whose function is still unknown. They can serve as good candidates for the design of a new series of lead compounds.
In addition to the 96-fragment library, other series of compounds of fragment-size were screened against Endothiapepsin (EP, Part IV) and different human Carbonic Anhydrase (hCA, Part V) isoforms. In particular, a series of tetrazole compounds were crystallographically screened against EP in order to validate a novel pipeline for the rapid development of novel aspartyl protease inhibitors using an anchoring approach. The hydrazide moiety was here chosen as fragment-anchor able to bind the catalytic dyad in the EP active site. Moreover, in addition to X-ray crystallography which was the dominant screening method used in the present thesis, a series of para-substituted benzenesulfonamide were screened against different hCAs isoforms using Surface Plasmon Resonance (SPR). According to Gaspari et al., the kinetics of binding of hCAII depend on the nature of the substituent that decorate the benzenesulfonamide moiety. In particular, the association rate kon becames faster by increasing the hydrophobic nature of the para-alkyl chain due to a pre-binding event. This finding was also confirmed in the present study. However, it seems that more than one features contribute to the trends in kon and koff. Furthermore, in contrast with hCAII, hCAXII showed a faster dissociation rate by increasing the length of the para-alkyl chain, probably due to the higher surface hydrophilicity. The nature of the surface around the active site of hCAs plays therefore an important role in the kinetics of binding. In conclusion, fragments are powerful molecules able to explore and discover new protein pockets, to evolve into more potent lead compounds and often they are used as starting point in several screening methods in the field of FBLD.Fragmente sind kleine organische Moluküle mit einer großen zahl funktioneller Gruppen, die in der Lage sind, verschiedene chemische Räume zu erforschen, in kleine Proteintaschen einzudringen und Proteinbindungsstellen zu finden. Heutzutage ist die Fragment-basierte Leitstrukturentwicklung(FBLD) die Methode der Wahl, um Bindungsstelle in Proteienen zu suchen und spielt eine immer wichtigere Rolle in der Medikamentenentwicklung. Daher ist es notwendig, eine universell
einsetzbare Fragmentbibliothek zu haben. In unserer Gruppe wurde eine 96-Fragment-Bibliothek an acht Protein-Targets validiert, die in einem Gemeinschaftsprojekt zwischen der HZB MX-Gruppe am BESSY II (AG Weiss) und dem Institut für Pharmazeutische Chemie der Universität Marburg (AG Klebe) entwickelt wurde (Part I). Unter den acht validierten Proteinen sind Thermolysin (TLN, Part II) und Trypanosoma cruzi Farnesyl Pyrophosphate Synthase (T. cruzi FPPS, Part III), die im Mittelpunkt der vorliegenden Studie standen. Die 96-Fragment-Bibliothek wurde daher als primäre röntgenkristallographische Screeningmethode zur Suche nach neuartigen chemischen Gerüsten eingesetzt. Allerdings musste vor dem Fragmentscreening ein neues Soaking-Protokoll erstellt werden. Tatsächlich haben die Fragmente im Gegensatz zum typischen TLN-Inhibitor in der Regel keine ausreichende Affinität, um das Autoproteolyseprodukt Val-Lys-Dipeptid, das das aktive Zentrum von TLN besetzt, allein zu verdrängen. Die Proteinkristalle wurden daher in einer Isopropanol-Lösung inkubiert, die in der Lage ist, das Dipeptid zu verdrängen, und anschließend gegen die Fragmentbibliothek gescreent, was zu sieben kristallographischen Fragmenthits führte. Im Gegensatz zu TLN, das üblicherweise als Modellprotein verwendet wird, ist T. cruzi FPPS ein Schlüsselenzym im Mevalonatweg beteiligt und für die Sterolproduktion unerlässlich ist. T. cruziund T. brucei-Parasiten verursachen die Chagas-Krankheit (CD) bzw. die humane afrikanische Trypanosomiasis (HAT). Die Hemmung von FPPS bei diesen Spezies ist daher ein gültiges Ziel zur Bekämpfung dieser beiden Tropenkrankheiten. Die vorliegende Arbeit konzentrierte sich zunächst auf die Optimierung der Stabilität von Proteinproben in Lösung unter Verwendung verschiedener Techniken wie dem Thermal shift-Assay (TSA) und der Lichtstreuung (LS). Anschließend wurde einKristallisations- und Soaking-Protokoll erstellt, bevor ein kristallographisches Fragmentscreening der oben erwähnten 96-Fragment-Bibliothek durchgeführt wurde. Darüber hinaus wurde auch die Rolle des Magnesium-Ions als Kofaktor des Enzyms aufgeklärt, entweder allein oder im Komplex mitIsopentenylpyrophosphat (IPP) oder Bisphosphonaten (BPs). Basierend auf der Entdeckung einer neuen allosterischen Tasche in humanem FPPS durch Jahnke et al. wurde angenommen, dass eine ähnliche Tasche auch in der Spezies Trypanosoma vorhanden ist, die daher Gegenstand der
vorliegenden Arbeit war. Das Fragment-Screening-Projekt ergab drei kristallographische Hits, von denen einer in die allosterische Tasche bindet, während die beiden anderen in einer neuen Tasche binden, deren Funktion noch unbekannt ist. Sie können als gute Kandidaten für das Design einer neuen Serie von Leitstrukturen dienen. Neben der 96-Fragment-Bibliothek wurden weitere Reihen von Verbindungen mit Fragment-Größe gegen Endothiapepsin (EP, Part IV) und verschiedene humane Carboanhydrase-Isoformen (hCA, Part V) gescreent. Insbesondere wurde eine Reihe von Tetrazol-Verbindungen kristallographisch gegen EP gescreent, um eine neue Pipeline für die schnelle Entwicklung neuer Aspartyl-Protease-Inhibitoren mit einem Verankerungsansatz zu validieren. Die Hydrazideinheit wurde hier als Fragment-Verankerung gewählt, die in der Lage ist, an die katalytische Dyade im aktiven Zentrum des EP zu binden. Zusätzlich zur Röntgenkristallographie, die in der vorliegenden Arbeit die dominierende Screeningmethode war, wurde eine Reihe von parasubstituiertem Benzolsulfonamiden gegen verschiedene hCAs Isoformen mittels Oberflächenplasmonenresonanz (SPR) gescreent. Nach Gaspari et al. hängt die Assoziationskinetik der Bindung von hCAII von der Art des Substituenten ab, den das Benzolsulfonamidgerüst trägt. Speziell wird die Assoziationsrate kon durch die Bildung eines hydrophoben Kontakts bestimmt, dessen Bildung mit der vergrößerten Oberfläche der Liganden begüntstigt wird. Dieser Befund wurde auch in der vorliegenden Studie bestätigt. Es scheint jedoch, dass mehr als ein Merkmal zu den Trends bei kon und koff beiträgt. Darüber hinaus zeigte hCAXII im Gegensatz zu hCAII eine schnellere
Dissoziationsrate durch die Verlängerung der para-Alkylkette, wahrscheinlich aufgrund der höheren Oberflächenhydrophilie. Die Beschaffenheit der Oberfläche um das aktive Zentrum von hCAs spielt daher eine wichtige Rolle für die Bindungskinetik. Zusammenfassend lässt sich sagen, dass Fragmente mächtige Moleküle sind, die in der Lage sind, neue Proteintaschen zu erforschen und zu entdecken, um zu potenteren Leitverbindungen entwickelt zu werden, und sie werden oft als Ausgangspunkt für verschiedene Screening-Methoden im FBLD verwendet
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