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Characterization of the folding of yeast frataxin: comparing hot and cold denaturation and defining the role of protein frustration
No full textUnderstanding the process leading a polypeptide chain to its native state is one of the unsolved
problems of modern Biochemistry. Even if the sequence of a protein contains all the information
necessary to guide the folding process, it has been demonstrated that the residual structure
eventually present in the denatured state can tune the folding process. For this reason, studying the
characteristics of the denatured state has become an useful tool to understand better the folding
process.
In this work the attention has been focused on yeast frataxin, a mitochondrial protein orthologous of
human frataxin, which is involved in several processes required for the cellular regulation of iron
homeostasis.
Yeast frataxin is an interesting system because it undergoes cold denaturation at physiological
conditions and at temperature above the freezing point of water. Therefore, it gives the chance to
study the folding process taking into account both the cold and hot denatured states.
The first part of this thesis is thus focused on the characterization of the hot and cold denaturation
processes. Analysis of thermal denaturation experiments and kinetic experiments revealed a simple
two state folding process. Then the transition states of the reaction have been characterized by using
a Φ-value analysis at two different temperatures, in combination with molecular dynamics
simulations. The differences in the cold and hot folding processes have been established by
comparing the structure of the denatured states with the one of the transition states.
The second part is focused instead on the characterization of another interesting aspect of yeast
frataxin: the competition between folding and function and its consequences for misfolding and
aggregation. Kinetic experiments have been performed on yeast frataxin by using urea as a
chaotropic agent. By analyzing the chevron plots obtained under different pH conditions, it has been
established that frataxin folds via a broad free energy barrier. This feature has been associated with
protein frustration and it gives the possibility to analyze both the early and late events of folding. In
order to do that, a Φ-value analysis has been performed and the data obtained have been used in
molecular dynamics simulations.
In this way it has been demonstrated that at the early stage of folding a significative fraction of
nonnative contacts can be observed. The prediction of molecular dynamics simulation has been
confirmed by a second round of mutagenesis, mutating those residues that are supposed to result in
non canonical Φ-values, confirming a high level of frustration in such regions and a propensity of
frataxin to misfold at the early stage of the folding process
Assessing customer centricity: a new framework for manufacturing companies
No full textAs a direct result of the changeable market conditions, manufacturing companies are currently shifting
their focus from goods to services. Given this process of servitization, customer’s needs and preferences are
becoming more and more relevant for companies. In this context, it becomes strategic and essential for companies
to adopt a customer centricity approach: a strategy that puts customer needs at the center of all business processes
and decisions. This paper aims to develop a new framework that identifies the elements characterizing the customer
centricity paradigm in manufacturing companies and supports companies in the evaluation of the customer
orientation level. Moreover, by applying the new framework in practice, this paper also discusses how it can helps
manufacturing companies in designing a structured customer centricity paradigm and in consistently identifying the
actions needed to implement it
Carlo Levi e il documentario italiano del secondo dopoguerra: influenze, suggestioni, immaginari.
No full textPercorso attraverso le influenze della letteratura e della pittura di Carlo Levi nel cinema documentario di matrice antropologica degli anni cinquanta e sessanta
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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