1,720,976 research outputs found
Functional and genetic studies in MEN2 and Hirschsprung disease
Get PDFHirschsprung disease (HSCR) and Multiple Endocrine Neoplasia type 2 (MEN2) are two seemingly unrelated neural crest-associated disorders that can be caused by germline mutations in RET. HSCR and MEN2 have distinct characteristics and different tissues are affected in each disease. However, in both diseases the basic problem is the disruption of signal transduction pathways required for normal physiological functions. This thesis presents a functional and genetic study on HSCR and MEN2, and aimed at unravelling the protein networks involved in the development of these disorders.
Part I of this thesis focuses on HSCR, which is an inherited disorder characterized by the absence of enteric neurons in the distal part of the colon. It can occur as an isolated trait, but is frequently associated with other congenita malformations present in rare, recessive syndromes. The study of the genes involved in these syndromes can yield new insights into the HSCR-related protein network and may help identify new HSCR candidate genes. One of these rare, recessive syndromes is called Goldberg-Shprintzen syndrome, for which mutations in KBP/KIAA1279 were found to be the causal entity. In Chapter 2 the function of the protein encoded by KBP/KIAA1279, the Kinesin-Binding Protein (KBP) was studied. Since the KBP function was largely unclear, we performed expression studies in zebrafish and found that KBP is expressed in the central and enteric nervous system. In addition, we showed that KBP is involved in neuronal differentiation and neurite outgrowth. In order to determine the KBP protein network, a yeast two-hybrid screen was performed.
Several kinesin-like proteins were found to interact with KBP, as expected. KBP was also found to interact with SCG10, a microtubule-destabilizing protein. This interaction was further confirmed by co-immunoprecipitation, co-localization and by epistasis experiments in zebrafih, thus linking KBP to microtubule dynamics. Since a direct interaction between KBP and microtubules could not be found, it is likely that KBP exerts its effect via SCGlO interaction
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
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
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