1,721,001 research outputs found
On-chip drug testing of an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor by kinase activity profiling.
No full textOn-chip drug testing of an aggressive intra-abdominal variant of inflammatory myofibroblastic tumor by kinase activity profiling.
No full textPeptide substrate-assisted study of O-GlcNAc transferase and O-GlcNAcylation
No full textO-GlcNAcylation is a post translational modification (PTM) that corresponds to the addition of a single β-linked N-Acetyl-D-glucosamine (GlcNAc) sugar moiety onto the hydroxyl group of serine and threonine residues in numerous proteins. The addition of O-GlcNAc to proteins is catalyzed by O-GlcNAc transferase (OGT), while its removal is catalyzed by O-GlcNAcase (OGA). In contrast to complex glycans that typically function on the cell surface by mediating numerous ligand-receptor interactions, O-GlcNAc modifications of proteins ubiquitously occur inside the cells where they regulate many basic cellular processes such as gene expression, cell cycle, metabolism, cellular stress response, insulin signaling, and proteostasis. Aberrant regulation of O-GlcNAcylation has been linked to chronic diseases such as type 2 diabetes, cancer and Alzheimer’s Disease (AD). Although advanced mass spectrometry and protein analysis techniques have been used for the study of O-GlcNAcylation of proteins, it is still a challenging task to study this modification at the protein level and in living systems. In this thesis, we studied O-GlcNAcylation at the peptide level, taking advantage of peptide chemistry and the power of peptide display techniques. We developed a dynamic peptide microarray approach to discover novel OGT substrates and study its catalytic properties. With this approach, the O-GlcNAcylation of hundreds of peptides immobilized on the microarray can be monitored in parallel by a fluorescent labeled anti O-GlcNAc antibody. Another important feature of this microarray-based assay is the kinetics readout of the O-GlcNAcylation process. This approach will likely prove valuable in diagnosis of GlcNAcylation-linked disease. The peptide microarray-based approach was further used to study the cross-talk between O-GlcNAcylation and tyrosine phosphorylation in a direct manner. From 256 known tyrosine kinase peptide substrates, we found that the phosphorylation of 6 peptides by Jak2 inhibited their subsequent O-GlcNAcylation while O-GlcNAcylation had no detectable effect on their subsequent phosphorylation. This type of crosstalk might prove to be more general with additional studies. These findings provide a glimpse of a possible new paradigm for cellular signaling control by cross-talk, although these results have to be validated on proteins and in living systems. Selective and potent inhibitors are valuable tools for deeper investigation of the biological functions of OGT. We found that two excellent OGT peptide substrates in which the O-GlcNAcylation site was replaced with an alanine, which can’t be O-GlcNAcylated, exhibited significant inhibitory effect on OGT activity. These data suggest that residues around the O-GlcNAc site maintain important interactions with the protein which could possibly be utilized to design selective OGT inhibitor. In addition, we used an mRNA display-based approach to discover short peptide substrates of OGT by taking advantage of its fast selection of peptides of interest from a library with a large diversity and complexity (5.12 x109 peptides). High-throughput sequencing of the selected libraries would yield information that can be used to compare the relative abundance of each sequence in the same selected population, which in our case might help identify the detailed substrate preference of OGT
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
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