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    Legemiddelindustriens troverdighet

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    Activation of ERK1/2 by the human 5-HT7 serotonin receptors

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    Receptor tyrosine kinases (RTKs) activate the mitogen-activated protein (MAP) kinases called extracellular signal-regulated kinases 1 and 2 (ERK1/2) through a signaling cascade involving proteins such as Shc, Grb2, SOS, Ras, Raf-1 and MEK. Activation of ERK1/2 directs proliferation and differentiation in a wide array of cell types. G-protein-coupled receptors (GPCRs) of many types have been shown to activate the ERK cascade, but the complete mechanisms are yet to be elucidated. Gs-coupled receptors activate adenylyl cyclase (AC) leading to a rapid increase in cyclic AMP (cAMP), and the main targets for cAMP are protein kinase A (PKA) and the Exchange Protein directly Activated by cAMP (Epac) specific for the small G-protein Rap1. It has been proposed for the Gs-coupled â2-adrenergic receptor that activation of ERK1/2 proceeds through Rap1 and B-Raf in a manner independent of Ras. However, for the human Gs-coupled serotonin receptors 5-HT4(b) and 5-HT7(a) it has been shown that ERK1/2 activation occurs independently of Rap1, relying instead on PKA and Ras. In this project we have explored various signaling mechanisms originating from the human Gs-coupled 5-HT7 serotonin receptors, with particular interest in the mechanisms of activation of ERK1/2. We demonstrate the activation of ERK1/2 in HEK293 cells transfected with 5-HT7(b) and 5-HT7(d) receptors subsequent to stimulation with serotonin. For the 5-HT7(b) receptors, we show that the observed activation of ERK1/2 is dependent on cAMP and Ras, but not on Epac and Rap1. Furthermore, direct cytosolic calcium measurements have shown that treatment with serotonin leads to a rapid but transient elevation in intracellular calcium in HEK293 cells stably transfected with 5-HT7(b) receptors, and the observed phosphorylation of ERK1/2 is mediated, at least partly, through a calcium-dependent pathway. We show that HEK293 cells endogenously express the Ras specific, Ca2+/calmodulin-dependent guanine nucleotide exchange factor Ras-GRF1. Ras-GRF1 becomes phosphorylated subsequent to 5-HT stimulation of 5-HT7(b) receptors, and it has previously been demonstrated that this phosphorylation enhances its towards Ras. This indicates that Ras-GRF1 has a role in the observed Ras-dependent activation of ERK1/2 mediated through 5-HT7(b) receptors

    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

    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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    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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