1,720,979 research outputs found
From High-Throughput Analysis of Genetic Variants to the Experimental Validation of Putative Protein Function
Get PDFThe state-of-the-art approach for the genetic molecular cause research relies on massively parallel gene sequencing, which represents a challenge both in data handling and variant prioritization. The univocal assignment of disease pathogenicity to the sequence variants is often difficult, and requires the integration of different lines of evidence for a comprehensive interpretation. During my thesis, I contributed to the development of novel approaches to evaluate rare variant contribution to the clinical phenotype. These methods were presented and evaluated at the Critical Assessment of Genome Interpretation, ranking among top programs considering either performance or the number of correct assigned disease predictions. A similar strategy was employed for identification of disease genes linked to neurodevelopmental disorders (NDDs) comorbidity. In this case, computational methods were applied to select the most promising candidate genes for the design of diagnostic panel, which is currently used for patient screening at Pediatrics Clinic of the University of Padova. The variants found within the panel genes have been selected according frequency, pathogenicity prediction and variant segregation analysis within the family. Furthermore, I took advantage of different computational tools to investigate the mutated gene function, and used this information to demonstrate the impact of likely pathogenic variant on clinical phenotype. In several cases, likely pathogenic mutations mapped to intrinsically disordered regions (IDRs), which lack a fixed three-dimensional structure. Coherently, several studies demonstrate that mutations in IDRs are often associated with the pathogenesis of various human diseases. Thus, IDRs classification could represent a critical step for understanding the impact of possibly disease-causative variants mapping in these regions. Due to the influence of intrinsically disordered proteins (IDPs) in diseases, I participated to the manual curation and update of entries in the DisProt database, the primary repository of disorder-related data on sequence. Interestingly, increasing evidence from literature highlights the IDPs involvement in neuronal signal transduction. Among the proteins encoded by diagnostic panel genes, TANC2 especially emerged as intrinsically disordered protein with a possible role in synaptic signal transduction. As TANC2 and its protein family function was poorly characterized, I performed an in silico analysis to characterize the TANC protein activity, and the implicated biological processes. The functional hypothesis emerged from the bioinformatics analysis was used to drive further experimental investigations. In vitro validation of predicted TANC2-CDKL5 interaction highlighted the relevance of the IDRs in regulating degradation of CDKL5, whose mutations are associated with a heterogeneous set of NDD phenotypes. Furthermore, I demonstrated that TANC2 contributes to downregulate CDKL5 expression levels. For this reason, TANC2 protein could represent a novel therapeutic target to design new drugs for the treatment of CDKL5 over-expression associated diseases
A case of reversible splenial lesion syndrome (Resles) related to neuroleptic malignant syndrome in a schizophrenic patient
Get PDFObjective: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological condition characterized by a transient lesion in the splenium of the corpus callosum. Method: A systematic search of the literature has highlighted a possible correlation between this rare condition and neuroleptic malignant syndrome (NMS) despite only few cases have been reported. Results: This paper reports a case of RESLES syndrome in a 36-years old male patient with NMS who was undergoing psychiatric treatment for schizophrenia. Conclusions: The reported clinical case highlights the possibility of including NMS as one of the differential diagnosis in RESLES syndrome
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
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
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