1,720,956 research outputs found
Suche nach Interaktionsgeometrien in Sammlungen von Proteinstrukturen
No full textDie vorliegende Arbeit beschreibt die Entwicklung von neuen Methoden zur Suche nach Interaktionsgeometrien in Proteinstruktursammlungen. Die Bindung zwischen einem Protein und einem kleinen Molekül oder zwischen zwei Proteinen ist ein fundamentaler Prozess in lebenden Zellen. Ein vollständiges Verständnis darüber warum zwei Moleküle binden und dessen Manipulation ist ein wichtiger Aspekt im Bereich des strukturbasierten Wirkstoffentwurfs. Die Basis von molekularer Bindung sind nicht kovalente Interaktionen zwischen Atomen. Methoden, die in der Lage sind die wachsende Menge an Daten nach geometrischen Präferenzen dieser Interaktion zu durchsuchen können helfen die treibenden Kräfte hinter diesen Bindungen besser zu verstehen. Existierende Methoden in diesem Feld bieten jedoch nicht genung Flexibilität und Präzision bezogen auf die möglichen Suchanfragen und in die analysierten Daten.
In dieser Arbeit wurden zwei Methoden entwickelt die das beschriebene Problem von verschiedenen Standpunkten betrachten. Die erste Methode (Pelikan) ermöglicht die Suche nach spezifischen Interaktionsmustern an der Schnittstelle zwischen Protein und Ligand. Damit können sogenannte Bioisostere und Chemoisistere entdeckt werden, die insbesondere dann von Nutzen sind, wenn spezifische Substrukturen in Liganden ausgetauscht oder mögliche Nebenenffekte eines Liganden vorhergesagt werden sollen. Die zweite Methode (NAOMI nova) berechnet geometrische Verteilungen von
interagierenden Atomen im Umfeld von molekularen Substrukturen aus Proteinstruktursammlungen.
Aus diesen Verteilungen können bevorzugte Interaktionsrichtungen abgeleitet werden, die beim Optimieren von Liganden und der Affinitätsvorhersage von Nutzen sind.
Beide Methoden benutzten eine server-lose Datenbank um die benötigten Daten effizient zu speichern. Hierfür wurden schnelle und flexible Suchverfahren entwickelt, die über existierende Methoden hinausgehen. Im Fall von Pelikan werden flexible und präzise 3D Anfragen auf atomarem Level unterstützt. Die Methode in NAOMI nova arbeitet mit benutzerspezifizierten molekularen Substrukturen und unterstützt verschiedene Attribute von Substrukturen und interagierenden Atomen in den Anfragen. Zusätzlich können die für die Suche genuzten Daten angepasst werden. Die Korrektheit, das Leistungsspektrum und die Anwendbarkeit beider Methoden werden in dieser Arbeit demonstriert. Darüber hinaus wurden grafische Oberflächen entwickelt, welche eine intuituve Benutzung durch Forscher aus dem Bereich der Lebenswissenschaften ermöglicht.The thesis at hand presents the development of new methods for the mining of interaction geometries in collections of protein structures. The binding between a protein and a small molecule or between two proteins is a fundamental event in all processes in living cells. Its complete understanding and manipulation is key in the field of structure-based drug design. The basis of molecular recognition are non-covalent interactions between atoms. Tools which can be used to mine the ever-growing data for specific spatial preferences of these interactions can help understanding the nature of molecular recognition. However, existing tools suffer from low variability and low precision of the used data and of the possible queries.
In this thesis, two methods have been developed which tackle the problem from two different perspectives. The first method, Pelikan, allows a user to search for specific interaction patterns in the interface between proteins and ligands. Using this methodology, bioisosters and chemoisosters can be found. This is particular useful if specific substructures in a ligand are to be replaced or a potential side-effect of a ligand is to be determined. The second method, NAOMI nova, calculates and presents distributions of interacting atoms in the vicinity of molecular substructures in collections of protein structures. From these distributions, preferred interaction directions can be deduced which is of major importance in the process of ligand optimization and affinity prediction during a drug design project.
For both methods, a serverless database system is used to efficiently store the relevant data. Fast and flexible retrieval systems have been developed for these database systems which go beyond existing methods. The retrieval system of Pelikan supports flexible as well as precise 3D queries on an atomic level. The NAOMI nova method handles user-defined molecular substructures and supports queries using different attributes of substructures and interacting atoms. In addition, the data used for the search processes is highly flexible and can be easily adapted. The correctness and the performance of the retrieval systems are demonstrated in this work and their applicability is shown in different examples. In addition, graphical user interfaces have been developed as part of this work which allow immediate and intuitive usage of the methods by life-science researchers
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
Re-Evaluating Exceptional Circumstances: Will IMS Create a New Legal Test for Compulsory Licensing?
No full textVariations 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
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