1,720,985 research outputs found

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    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

    Systematic interaction interface and variant characterization using protein interaction profiling

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    Eine vielversprechende Strategie, das Edgotyping, nutzt Protein-Protein-Interaktionsnetzwerke (PPI) zur systematischen Charakterisierung von Varianten und zur Aufdeckung von Krankheitsmechanismen, indem getestet wird, wie sich pathogene und nicht charakterisierte Mutationen auf Proteininteraktionen auswirken (Vidal et al. 2011; Sahni et al. 2013; Sahniet al. 2015; Fragoza et al. 2019; Cheng et al. 2023). Es wurden mehrere Versuche mit dem Edgotyping-Ansatz durchgeführt. So identifizierten Sahni et al. (2015) 197 Mutationen in 89 Wildtyp-Proteinen, wobei 26% einen vollständigen Verlust der Interaktion aufwiesen, 31% edgetisch waren und 43% unverändert blieben, unter Verwendung von Y2H. Unter Verwendung desselben Ansatzes bewerteten Fragoza et al. (2019) 1.676 Missense-Varianten in 4.109 Protein-Varianten-Interaktionen und identifizierten 298 störende Varianten, die 669 PPIs betreffen, und untersuchten deren funktionelle Auswirkungen. Dieser experimentelle Ansatz hat das Potenzial, uncharakterisierte Varianten zu adressieren, bleibt aber aufgrund der großen Anzahl dieser Varianten teuer und arbeitsintensiv. In dieser Arbeit wird eine systematische Strategie zur Charakterisierung von Varianten an- hand von vorhergesagten und experimentell validierten DMI-Schnittstellen durch PPI-Profiling vorgeschlagen. Kapitel 2 befasst sich mit der Erstellung der ORFeome-Sammlung, der Bewertung der BRET-Empfindlichkeit und der Entwicklung einer Klonierungspipeline mit mittlerem Durch-satz sowie eines BRET-basierten Assays zur experimentellen Validierung von DMIs. Artikel I zeigt die erfolgreiche Anwendung von Klonierung und ortsgerichteter Mutagenese mit geringem Durchsatz, gefolgt von BRET-Assays mit mittlerem Durchsatz, um DMI-vermittelte PPIs, die am Spleißen beteiligt sind, experimentell zu validieren. Artikel II stellt eine optimierte plattenbasierte Klonierungspipeline und einen BRET-Assay zur Validierung neuartiger vorhergesagter Schnittstellen und zur Analyse von Mutantenpositionen und deren Potenzial zur Unterbrechung dieser Schnittstellen vor, basierend auf vorhergesagten Schnittstellenstrukturen aus AF-MM. Somit zeigen sowohl Artikel I als auch Artikel II die Etablierung eines systematischen Ansatzes für die experimentelle Validierung mutmaßlicher DMIs. Kapitel 3 beschreibt die Entwicklung des DMI-Prädiktors und seine Anwendung bei der Vorhersage und Kartierung dieser DMIs anhand von HuRI-PPI-Daten, gefolgt von der Integration von ClinVar-Mutationsdaten mit vorhergesagten DMIs. Außerdem wird die Auswahl der PPIs beschrieben, die mit DMIs kartiert wurden und für eine experimentelle Validierung geeignet sind. Im Ergebnis konnten wir 46 von 96 PPIs mit dem BRET-Assay bestätigen. Von diesen haben wir die vorhergesagten DMIs von 22 Interaktionen weiter ausgewertet und 6 Kandidatenproteine (CTBP1, WWOX, PPP3CA, REPS1, SPOP und IQCB1) identifiziert. Dies zeigt, dass die Integration von DMI-Informationen mit der Erstellung von Proteininteraktionsprofilen dazu beitragen kann, Varianten zu charakterisieren, unser Verständnis der Auswirkungen von Varianten auf PPIs zu verbessern und tiefere Einblicke in die Mechanismen dieser Varianten und ihre potenziellen Beiträge zu Krankheiten zu liefern.263 Seiten ; Diagramm

    Variations on the Author

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    “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

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    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

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    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

    Author Index

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    On the characterization of protein interaction interfaces with computational approaches and experimental validations

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    Proteins play crucial roles in virtually all cellular processes, and their functions are of- ten realized through interactions with other proteins via different interfaces. Thus, for a comprehensive understanding of protein functions, it is important to investigate the molecular mechanisms of protein-protein interactions (PPIs) by characterizing their interaction interfaces. Unfortunately, due to most high-throughput assays detecting only PPIs and not their interfaces, mechanistic information is scarce for most PPI data. The current thesis presents a collection of studies exploring the characterization of different types of PPI interfaces in the human protein interactome. Domains and motifs are two types of conserved functional modules that enable PPIs by forming domain-domain interfaces (DDIs) and domain-motif interfaces (DMIs). Chapter 2 and Article I delved into the characterization of DMIs and DDIs in PPIs by leveraging information from existing databases. Chapter 2 centered on automating the detection and scoring of DMIs in PPIs through a computer program. Article I focused on evaluating the DDIs annotated in the 3did database by manually curating a reference dataset of DDIs and identifying useful features to further score them. The program developed in Chapter 2 and the high-confidence DDIs from 3did were applied to PPIs detected in the human protein interactome to characterize their interfaces. AlphaFold-Multimer (AF-MM) is an artificial intelligence (AI)-based tool for pre- dicting the structures of protein complexes. Article II and III investigated the use of AF-MM to predict novel PPI interfaces. As there is a lack of a comprehensive as- sessment of AF-MM and its metrics, Article II systematically benchmarked AF-MM’s ability to predict different types of interfaces and established criteria for discriminat- ing good from bad structural models. Testing AF-MM using sequences longer than minimal interacting regions revealed that they are detrimental to AF-MM’s prediction performance, prompting the development of a fragmentation-based approach to en- hance AF-MM’s sensitivity. The approach was applied to PPIs detected in the human protein interactome to predict their interfaces, and some predicted interfaces were ex- perimentally validated. Similarly, article III applied the fragmentation approach on a protein pair whose interaction is important for piRNA amplification. Subsequent experimental validation also confirmed the interaction interface predicted by AF-MM. This thesis provides various approaches to leverage existing knowledge on different PPI interface types to predict PPI interfaces in the human protein interactome, paving the way towards a mechanistically annotated human protein interactome.vii, 207 Seiten ; Illustrationen, Diagramm

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    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
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