1,721,013 research outputs found
The Dynamics of the Chaperone Folding Machinery
No full textLe proteine chaperone, una famiglia di cui Hsp90 e Hsp70 sono membri fondamentali, formano un meccanismo essenziale per mantenere sano il proteoma, controllando il folding e l'attivazione di proteine substrato, dette client. Ciò avviene attraverso un processo in cui le chaperone sono finemente regolate da specifici co-chaperoni, ciclo ATPasico e modifiche post-traslazionali (PTMs). Nonostante gli impressionanti progressi nelle tecniche di risoluzione strutturale, i meccanismi alla base dei diversi livelli di regolazione rimangono ancora elusivi. In questa tesi indagheremo la dinamica del meccanismo di folding delle chaperone mediante simulazioni di dinamica molecolare (MD). Integrando simulazioni ed esperimenti abbiamo studiato gli effetti di singole PTM sulla chaperone Grp94 (glicosilazione) e sul co-chaperone Hop (fosforilazione). Attraverso una combinazione di simulazioni all'equilibrio e fuori equilibrio, abbiamo svelato importanti dettagli alla base del meccanismo di regolazione da parte dei nucleotidi nel complesso macchinario delle chaperone. Abbiamo guidato computazionalmente lo sviluppo di chemical tools in grado di legare sia Hsp70 che Hsp90, i quali rappresentano la base per la progettazione di inibitori a doppia azione. Nel complesso, questa tesi aggiunge importanti tasselli al puzzle del chaperone code: dall'illuminazione dell'esclusiva regolazione glicosidica di una chaperone allo sviluppo di chemical tools a doppia azione.Chaperone proteins, a family of which Hsp90 and Hsp70 are integral members, form an essential machinery to maintain healthy proteomes by controlling the folding and
activation of a plethora of substrate client proteins. This is achieved through cycles in which chaperones are finely regulated by task-specific co-chaperones, ATP processing and Post-Translation Modifications (PTMs). Despite impressive advances in structural knowledge, the mechanism underlying the different levels of regulation still remain elusive. In this thesis, we investigate the dynamics of the chaperone folding machinery by means of Molecular Dynamics (MD) simulations. We integrate simulations and experiments to unveil the effects of single PTMs on the Endoplasmatic Reticulum paralog of Hsp90, namely Grp94 which is modified by glycosylation and on the co-chaperone Hop, modified by phosphorylation. Through a combination of equilibrium and out-of-equilibrium MD simulations, we unveil with unprecedented detail the mechanisms that underpin nucleotide signalling in chaperone machineries. Furthermore, we computationally design the development of chemical tools able to bind both Hsp70 and Hsp90, which represent the first reported dual-acting inhibitors. Overall, this thesis adds important pieces to the puzzle of the chaperone code: from the illumination of unique PTM regulation mechanisms of a chaperone to the development of dual-acting chemical tools
Il contributo di Giorgio Amendola alla formazione del pensiero europeista del Pci: una prospettiva di indagine storica (1962-1980)
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il "dominio economico tedesco" e la propaganda antieuropea ai tempi della Guerra fredda: il caso italiano
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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
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