1,720,956 research outputs found
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
Unterschiedliche Autoregulation am PU.1 Lokus in B -Zellen und myeloischen Zellen
Get PDFAls Schlüsselfaktor des hämatopoietischen Systems spielt PU.1 eine ent-scheidende Rolle in der Entwicklung der meisten hämatopoietischen Li-nien. Das PU.1 Expressionslevel bestimmt das Differenzierungspotential hämatopoietischer Stammzellen und Vorläufer. In den unterschiedlichen Zelltypen werden verschiedene Expressionsstärken etabliert. Wie diese zelltypischen Expressionslevel vonPU.1 generiert werden, ist bisher weit-gehend unbekannt. In der vorliegenden Doktorarbeit wurde mit Hilfe eines transgenen Maus-modells die cis-regulatorische Einheit von PU.1 definiert, um mit nachfol-genden molekularbiologischen und genomweiten Ansätzen Mechanismen der zellspezifischen Regulation von PU.1 zu aufzuzeigen. Die Definition der cis-regulatorischen Einheit von PU.1 erfolgte mit Hilfe eines transgenen Mausmodells, welches ein humanes PU.1 BAC Kons-trukt trägt. Es konnte gezeigt werden, dass humanes und murines PU.1 substituierbar sind und den gleichen Regulationsmechanismen unterlie-gen. Mit Hilfe genomweite DNaseI hypersensitivity Analysen, Methylie-rungs- und Bindungsstudien konnte ein neuer Regulationsmechanismus beschrieben werden, der eine spezifische kombinatorische Interaktion verschiedener cis-regulatorischer Elemente erfordert. Durch Reportergenassays in verschiedenen Zelltypen war es möglich, einen myeloischen Enhancer zu identifizieren. Es konnte gezeigt werden, dass PU.1 mit zelltyp-spezifischen Transkriptionsfaktoren interagiert, um unterschiedliche Bindungsmuster an seinen regulatorischen Elementen zu etablieren. Dadurch kommt es zu den spezifischen Expressionstärken von PU.1The transcription factor PU.1 occupies a central role in controlling myeloid and early B cell development and its correct lineage-specific expression is critical for the differentiation choice of hematopoietic progenitors. However, little is known of how this tissue-specific pattern is established. We previously identified an upstream regulatory cis-element (URE) whose targeted deletion in mice decreases PU.1 expression and causes leukemia. We show here that the URE alone is insufficient to confer physiological PU.1 expression, but requires the cooperation with other, previously unidentified elements. Using a combination of transgenic studies, global chromatin assays and detailed molecular analyses we present evidence that PU.1 is regulated by a novel mechanism involving cross-talk between different cis-elements together with lineage-restricted autoregulation. In this model, PU.1 regulates its expression in B cells and macrophages by differentially associating with cell-type specific transcription factors at one of its cis-regulatory elements to establish differential activity patterns at other elements
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
Analysis and prediction of selectivity in biological and chemical space
Get PDFSmall molecules can be designed to interact with a specific protein or proteins, and, by
extension, to modulate the biological pathways in which the respective protein is involved. Small molecules can thus influence a disease phenotype on a cellular, tissue, or
organism level. However, some compounds, so-called ‘promiscuous’ compounds, modulate the phenotype by binding to a wide range of on- and off-targets. In the case of
drugs, this binding to off-targets can be responsible for side effects, as the perturbation
of other biological pathways can lead to severe or even lethal side effects. ‘Selective’
compounds target only one protein or a small set of closely related targets, the ‘ontargets’, at a given bioactivity range. Contrary to promiscuous small molecules, they
should have a low number of off-targets.
The selectivity or promiscuity of a compound is dependent on both protein and ligand
structural features. I am the first to explore the inclusion of individual residue movement
as a descriptor in random forest models. Using simple 2D flexibility descriptors, I
show that I can identify flexible regions, depending on the data set. However these
flexibility values are too uniform and coarse to be used as descriptors in the random
forest algorithm to identify up discriminating features.
I also show that the current 2D random forest models and the available kinase data are
sufficient to correctly predict the activity of selective compound-target pairs depending
on previous data.
Lastly, I investigated the use of 3D protein-ligand interaction features in filtering out
selective (and promiscuous) compounds and the use of interaction grids to classify candidate compounds in different binding affinity ranges. Both promiscuous ligands and
selective compounds active against closely related targets tend to have a conserved binding mode across their kinase targets. Additionally, binding features cannot be used to
separate strong or weak binders for a given target ; however, a separation based on a
3D grid might be promising.
However, from a biological perspective, the often unknown involvement of a target in
other pathways (‘pathway crosstalk’) might add confounding biological readouts and
thus unexpected side effects, even if the compound is selective against the target of
interest. Hence, I explored drug targets from a pathway-centric perspective. I show
that the overall number of pathways associated with all drug targets of a drug does
not correlate with its success or its withdrawal. Lastly, I show that - depending on
target class - drug targets are generally associated with a wider range of pathways
than ‘undrugged’ proteins, highlighting either a research bias towards drug targets or
possibly that drug targets are chosen due to a higher involvement in pathway crosstalk.
I also found that pathways could be targeted for the same disease area using multiple
associated targets, thus highlighting a potential for finding novel drug targets outside
the traditional ‘target class’-centric paradigm.
In conclusion: in order to study selectivity, I have focused on a widely studied target
class, namely kinases. My results indicate promise in using 3D-based selectivity models
to derive kinase inhibitors, especially combined with the use of a standardized nomenclature across kinase binding pockets. Secondly, I also show the necessity of using a
more ‘pathway-centric’ exploration of drug targets instead of the current, traditional
‘target class’-centric approaches
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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