1,720,962 research outputs found
Mechanistic Studies on the Copper-Catalyzed N-Arylation of Amides
No full textThe copper-catalyzed N-arylation of amides, i.e., the Goldberg reaction, is an efficient method for the construction of products relevant to both industry and academic settings. Herein, we present mechanistic details concerning the catalytic and stoichiometric N-arylation of amides. In the context of the catalytic reaction, our findings reveal the importance of chelating diamine ligands in controlling the concentration of the active catalytic species. The consistency between the catalytic and stoichiometric results suggests that the activation of aryl halides occurs through a 1,2-diamine-ligated copper(I) amidate complex. Kinetic studies on the stoichiometric N-arylation of aryl iodides using 1,2-diamine ligated Cu(I) amidates also provide insights into the mechanism of aryl halide activation.National Institutes of Health (U.S.) (GM 58160)American Chemical SocietyMerck & Co., Inc.Novartis (Firm
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
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Elucidating the Molecular Mechanism of the Proteasome-Associated Deubiquitinase UCH37/UCHL5
No full textDeubiquitinases (DUBs) are a group of enzymes that regulate myriad biological processes by removing ubiquitin posttranslational modifications. They can either cleave ubiquitin directly from a substrate protein or disassembling a ubiquitin chain. Currently, about 100 human DUBs were identified and they were classified into seven families, and majority of them are cysteine proteases. DUBs exhibit distinct activities and preferences towards a wide variety of complex Ub chain with different linkages and architectures. Understanding how DUB achieves the selectivity towards specific substrates is important to elucidate how Ub system is regulated. This dissertation discusses our efforts to investigate the molecular mechanism of DUB, specifically the proteasome associated DUB UCH37/UCHL5. We have combined biochemical assay, biophysical characterization, mass spectrometry, and cell biology to address how DUB interacts with different ubiquitin chains to achieve substrate specificity. These lead us to uncover a novel mechanism that DUBs may use distinct surfaces for distinct activities. Finally, the discovery of the new mechanism of DUB would also provide new avenues for the DUB inhibitors development for therapeutics.ChemistryDoctor of Philosophy (Ph.D.
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
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Utilizing Mass Spectrometry to Study Ubiquitination and Degradation
No full textProtein ubiquitination is a post-translational modification that affects many aspects of cellular processes, including the stability of proteins, activation of cellular signaling pathways and response to DNA damage. This versatility arises from the ability of ubiquitin (Ub) to form structurally and functionally distinct polymers, using one of the seven lysine residues (K6, K11, K27, K29, K33, K48, K63) or the N-terminal methionine, M1, through an enzymatic cascade involving Ub-activating (E1), Ub-conjugating (E2), and Ub-ligase (E3) enzymes. These Ub subunits can be extended in homotypic Ub chains, where all linkages are the same chain type, or heterotypic Ub chains that comprise alternating linkage types or branches. This dissertation introduces new methods for studying the formation and cleavage of branched Ub chains. Complementary approaches of biochemistry, mass spectrometry, and cell biology were utilized to 1) quantitate the formation of phosphorylated heterotypic chains, 2) elucidate the debranching activity of UCH37, and 3) detail a method in isolating specific proteasome complexes to investigate proteasomal-bound deubiquitinases. These findings contribute to the growing information about branched Ub chains that will aid in the development of biochemical strategies for studying their impact in many cellular processes.ChemistryDoctor of Philosophy (Ph.D.
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ELUCIDATING THE INTERACTIONS OF K48-LINKED UBIQUITIN CHAINS WITH UCH37/UCHL5
No full textDegradation of proteins by the 26S proteasome is a highly regulated process that is mediated by the type of ubiquitin (Ub) modification present on the substrate. Ub can form polyubiquitin chains by modifying itself on any of its seven surface Lys residues and the N-terminal Met. This leads to a multitude of different chain architectures that can decorate substrates. Branched Ub chains, where a single Ub is modified at two different sites, have been shown to be particularly potent signals for degradation. UCH37 is a proteasome associated deubiquitinase (DUB), which is recruited to the proteasome by RPN13. Our lab has shown that the UCH37-RPN13 complex selectively cleaves K48 linked chains when they are part of a branch point, thereby promoting degradation. This thesis addresses how this enzyme selectively binds to K48 linked chains and discriminates between branched and nonbranched ubiquitin. For this we utilized a number of biophysical techniques including HDX-MS, NMR, chemical crosslinking and molecular docking. Our results uncover a novel ubiquitin binding site on the α5-α6 motif of iv UCH37. This site is required for K48 chains binding and debranching. Our results also suggest that two binding poses are possible for a K48 linked chain, however only one pose is likely to enable debranching. Furthermore, using NMR spectroscopy, we also studied the interactions of a K6/K48 branched trimer with UCH37. We have shown that all three subunits of the trimer interact with the enzyme and show unique chemical shifts. We identified a unique set of peaks in the K48-distal subunit of the branched trimer corresponding to a conformation unique to the branched trimer when in complex with UCH37. Our results suggest that stabilization of this unique conformation could be the explanation for branched point selectivity.ChemistryDoctor of Philosophy (Ph.D.
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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