1,720,990 research outputs found
Characterization of disturbed neural crest migration as mechanism of developmental toxicity of prescription drugs
No full textIn the last years, different individual human embryonic stem cell-based developmental toxicity test systems have been established and have been proven to offer new possibilities to explore toxicological hazard directly on relevant and non-transformed human cells. A further achievement has been the combination of these assays to comprehensive batteries able to predict human developmental toxicity. In the framework of the European project ESNATS (Embryonic Stem cell-based Novel Alternative Testing Strategies), we developed a test battery which allows the inclusion of any developmental toxicity assay, and that explores the responses of such test systems to a wide range of compounds. As a first step, we selected and characterized a heterogeneous group of compounds with a wide applicability domain, which ranged from environmental pollutants to several prescription drugs. To evaluate the feasibility of the suggested test framework, we performed the initial screen in a well-characterized assay that evaluates ‘migration inhibition of neural crest cells’ (MINC assay), which finally resulted in the identification of 11 hits (e.g. geldanamycin, arsenite, PBDE-99). Next, transcriptome analysis for some selected MINC hits was performed. The transcriptome changes triggered by these substances in human neural crest cells (NCC) were recorded and analyzed. Transcript profiling allowed a clear separation of different toxicants. Furthermore, a diagrammatic system was developed to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. KEGG pathways or overrepresented gene ontology terms). Finally, the transcript data were mined for potential markers of toxicity. We found that the inclusion of transcriptome data largely increased the information from the MINC phenotypic test. As a final step, one of the MINC-positive compounds, the prescription drug interferon-β (IFNβ), was chosen to be further characterized as potential developmental toxicity hazard. We could confirm the adverse effects of IFNβ on NCC migration in different functional assays. The analysis of transcriptome changes suggested a role of altered JAK-STAT signaling in toxicity, which was confirmed by detailed measurements of interferon effects on signaling in the presence of specific kinase inhibitors.publishe
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
Variations 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
On the usefulness of animals as a model system (part II) : Considering benefits within distinct use domains
No full textIn many countries, animal experiments can only be performed when their necessity has been demonstrated in a legal document. As the usefulness of animals in research is also a significant societal and political issue, criteria to structure debates and evaluations are needed. Here, background information is given on laboratory animal studies. Moreover, parameters that may be considered in judging their usefulness are suggested. The discussion is strictly focused on animals used as tools/test systems/models to provide information on humans. In this context, general features and performance characteristics of models are discussed. Examples are given for well-recognized criteria (e.g., robustness, relevance, predictivity) to judge the usefulness of predictive models. The main hypothesis put forward here is that a benefits evaluation (usefulness metrics) is only possible within sharply circumscribed "use domains". Examples are given for the research fields of drug and vaccine research, toxicology, disease pathogenesis, and basic biological research. Efficacy, safety, and quality studies are highlighted as "use domains" within the field of drug discovery and production. A further separation into individual diseases, drug targets or symptoms is suggested for, e.g., efficacy studies or pathophysiology. Finally, an outlook is given on the evaluation of model advantages and disadvantages to arrive at their "net benefit". Moreover, the need to compare the net benefits of animal models versus that of their alternatives is highlighted.publishe
- …
