1,720,973 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

    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

    Generation and characterisation of laminopathy-specific antibodies

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    Laminopathien sind eine Gruppe von Krankheiten die hauptsächlich von Mutationen in den A-typ Laminen verursacht werden. Die meisten dieser Mutationen verursachen einen Austausch von nur einer Aminosäure, die meistens autosomal-dominant vererbt werden. Die molekularen Mechanismen von Laminopathien und deren Krankheitsursache, sind aufgrund des Fehlens von spezifischen Forschungswerkzeugen, die das Studieren von den mutanten Proteinen in Patientenzellen erlauben würden, hingegen nur wenig bekannt. Basierend auf dem Ergebnis, dass die im Ogris Labor entwickelten Antikörper gegen Isoformen von Protein Phosphatase 2A (PP2A) Untereinheiten zwischen Isoformen unterscheiden können, die sich nur in einer Aminosäure des entsprechenden Epitops unterscheiden, meinten wir, dass es möglich wäre Antikörper zu entwickeln, die spezifisch das Wildtyp oder die mutanten A-typ Laminproteine, die sich nur in einer Aminosäure unterscheiden, erkennen würden. Solche Antikörper wären für die detailierte Charakterisierung des pathologischen Zustandes und zur Aufklärung der Krankheitsenstehung auf zellulärer Ebene sehr hilfreich. Deshalb hatten wir die Absicht, monoklonale Antikörper spezifisch für autosomal-dominant Emery Dreifuss Muskuläre Dystrophie (EDMD), familiäre partielle Lipodystrophie (FPLD), und dilatierte Kardiomyopathie (DCM) verursachende Punktmutationen in den A-typ Laminen zu entwickeln, die es erlauben würden, zwischen Proteinen, die nur in einer einzigen Aminosäure verschieden sind, zu unterscheiden, um so die speziellen molekularen Eigenschaften des Wildtyp oder des mutanten Proteins zu untersuchen. Um zu solchen Antikörpern zu gelangen wurden drei Ansätze der Antigenpräsentation angewandt. Diese inkludierten den Gebrauch von kurzen Peptiden gekoppelt an das Keyhole limpet hemocyanin (KLH) Protein, rekombinante Proteine bestehend aus der Lamin A/C C-terminalen Ig-fold Domäne fusioniert mit dem Hepatitis B Virus Core Protein (HBcAg), und rekombinante Proteine bestehend aus kurzen Peptiden, mit den gewünschten Lamin A/C Epitopen, fusioniert an HBcAg. Die Entwicklung eines EDMD relevanten punktmutation-spezifischen Antikörpers gegen die Lamin A/C Mutante R453W war mit dem KLH-Peptid Ansatz erfolgreich. Zusätzlich wurde ein Lamin A/C Ig-fold spezifischer monoklonaler Antikörper entwickelt. Bedeutend ist auch, dass Immunisierungen mit dem rekombinanten HBcAg-lamin A/C Ig-fold R482W Fusionsprotein zu einem punktmutations-spezifischen Antikörper führten. Das deutet darauch hin, dass Immunisierungen mit einer ganzen Proteindomäne eine punktmutation-spezifische Immunantwort auslösen können. Bedeutend ist, dass Experimente mit primären EDMD Patientenzellen zeigten, dass der neu entwickelte anti-Lamin A/C R453W Antikörper spezifisch die mutanten Proteine immunpräzipitieren, und die mutanten Proteine in der Immunfluoreszenz und im Immunblotting detektieren konnte. Mit dem anti-lamin A/C R453W Antikörper werden Funktionen der mutanten A-typ Lamine in primären Zellen von EDMD leidenden Patienten untersucht.Laminopathies are a group of diseases caused mainly by mutations in A-type lamins. The vast majority of these mutations cause single amino acid substitutions inherited in an autosomal-dominant way. The molecular mechanisms of laminopathies and their etiology, however, are still poorly understood, mostly because of the lack of specific research tools to study the mutant proteins in patient cells. Based on the finding from the Ogris lab that antibodies against protein phosphatase 2A (PP2A) subunit isoforms can discriminate between isoforms differing only in one amino acid at the respective epitope, we thought that it would be feasible to develop antibodies recognizing specifically the wild-type or the mutant A-type lamin proteins, which are differing only in one amino acid. These antibodies would be extremely helpful for a detailed characterization of the pathological conditions and the elucidation of the disease pathogenesis at the cellular level. Therefore we aimed to develop mouse monoclonal antibodies specific for autosomal-dominant Emery Dreifuss Muscular Dystrophy (EDMD), Familial Partial Lipodystrophy (FPLD), and Dilated Cardiomyopathy (DCM) causing point-mutations in the A-type lamins, which would allow to distinguish between proteins differing in a single amino acid, and thus to study the special molecular features of the wild-type and the mutant proteins, respectively. To obtain such antibodies we made use of three different approaches of antigen presentation. These include the use of short peptides coupled to the keyhole limpet hemocyanin (KLH) protein, recombinant proteins consisting of the lamin A/C C-terminal Ig-fold domain fused to the Hepatitis B virus core protein (HBcAg), and recombinant proteins consisting of short peptides corresponding to the desired lamin A/C epitopes fused to HBcAg. We were successful in developing an EDMD relevant point-mutations specific antibody against the lamin A/C mutant R453W by the KLH-peptide approach. In addition, a lamin A/C Ig-fold specific monoclonal antibody was developed. Importantly, we could also show that a recombinant HBcAg-Lamin A/C Ig-fold R482W fusion protein elicited a humoral immune response resulting in the production of lamin A/C R482W point-mutant specific antibodies, indicating that immunizations with a whole protein domain can elicit a point-mutant specific immune response. Importantly, experiments using primary EDMD patient cells showed that the newly developed anti-lamin A/C R453W antibody could be used to specifically immunoprecipitate the mutant proteins, and to detect the mutant proteins in immunofluorescence and immunoblotting. The anti-lamin A/C R453W antibody will be used to examine the functions of the mutant A-type lamins in primary cells from EDMD patients

    Endothelial CCR2 Promotes Pulmonary Metastasis

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    Nine out of ten cancer patients die due to metastasis. The generation of them is dependent on several factors, including the recruitment of inflammatory monocytes and activation of endothelial cells at the pre-metastatic niche. It is at these sites where cancer cell seeding of the targeted secondary tissue is taking place. Inflammatory chemokines, especially the chemokine ligand CCL2 and its receptor CCR2, are regulating several aspects of the metastatic cascade, including monocyte recruitment to the metastatic niche and induction of vascular permeability enabling cancer cell trans-endothelial migration. We aimed to target the CCL2-CCR2 signaling axis at the pre-metastatic niche by pharmacological inhibition and a genetic endothelial specific CCR2 knockout (CCR2ecKO) mouse model. A mutant signaling deficient dnCCL2-HSA chimera strongly inhibited cancer cell trans-endothelial migration as well as cancer cell seeding to the lung. As a consequence the metastatic burden was strongly decreased in dnCCL2-HSA treated mice. The anti-metastatic effect of dnCCL2-HSA was dependent on its inhibition of cancer cell induced vascular permeability, while recruitment of inflammatory monocytes to the pre-metastatic niche was not impaired. dnCCL2-HSA was found to be present in close proximity to cancer cells in the lung vasculature, indicating that local inhibition of CCR2 signaling is sufficient to prevent metastasis initiation. Furthermore, targeting of cancer cell activated endothelial cells by VCAM-1 binding peptide equipped liposomes loaded with a CCR2 antagonist confirmed that inhibition of CCR2 at sites of activated endothelium is sufficient to prevent the generation of metastases. The spatial inhibition of CCR2 using these liposomes interfered with induction of vascular permeability, but spared any detectable effects on inflammatory monocytes. The endothelial specific CCR2 knockout (CCR2ecKO) mouse model confirmed findings from both inhibitor approaches. Spontaneous lung metastasis was strongly reduced in CCR2ecKO mice compared to control littermates. Leukocyte recruitment to the primary tumor, the pre-metastatic niche, and the metastatic environment however, was not affected due to the endothelial CCR2 knockout.Stimulation of endothelial cells with CCL2 caused phosphorylation of MLC2, which is required for endothelial cell retraction. Overall we could show that endothelial CCR2 is the gatekeeper for cancer cell trans-endothelial migration and thus represents the final check-point for metastasis initiation of colon and lung cancer cells. Targeting endothelial CCR2 at pre-metastatic sites represents a promising treatment strategy to prevent cancer cell seeding and thus metastatic spread to the lung

    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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