3,258 research outputs found
Insulin signaling network: mathematical modeling and parameter estimation from experimental data
No full textThe insulin signaling network (ISN) is an important metabolic network that, upon the insulin binding to its receptor at the cell surface, triggers the glucose uptake into the cell. The study of this mechanism within muscle cells, hepatocytes and cells of the adipose tissue is of major interest since it is crucial for understanding more clearly the factors that may induce the insulin resistance. However, the structure and the behaviour of the insulin signaling network are only partially known and the current research on this topic is
fragmented into various lines of investigation. Because of the high degree of complexity of the ISN, it is diffcult to understand, without a theoretical framework, how the network responses evidenced from the experimental data determine the cell behaviour.
In the present thesis, we proposed a detailed mathematical model of the ISN in order to investigate the factors that affect the basal concentrations and the dose-response curves (i.e., the steady state concentrations at given insulin levels) of the main components of the whole network. Our model concentrated particularly on single and double phosphorylation of Akt protein, and hypothesized the existence of a putative factor released by the small intestine that induces insulin resistance by activating the mammalian target
of rapamycin complex 2 (mTORC2) in an insulin-independent manner and possibly operating through the IGF-1 receptor. Such hypothesis is based on clinical and experimental observations.
The parameters of the ISN model were estimated from the experimental data of two skeletal muscle cell lines using a least squares approach. As the available data consisted in the equilibrium concentrations of many of the known signaling components at given values of the insulin, we derived the concentrations of the chemicals at the steady-state from the kinetic equations and then we implemented an algorithm that minimizes the distance between the model outputs and the data. For the numerical solution, we used a local optimization routine based on a derivative-free algorithm for bound constrained optimization.
The ISN model was able to adequately fit the available experimental data. The model could thus become a useful tool to generate and test hypotheses, leading to a deeper understanding of the molecular mechanisms underlying insulin resistance and, in future perspective, to find drugs able to counterbalance the effects of this disease.
Finally, as it is now widely recognized that Akt and mTOR complexes have a major role also in the regulation of cell proliferation, and then in cancer development, we combined the ISN model with a mathematical model that described the evolution of a AML (acute myeloid leukemia) cell population in order to investigate the effects of mTOR inhibitors with antitumor activity on the ISN and on the cell population response. Based on literature data of AML cell response to mTOR inhibitors with antitumor activity (the dual ATP-competitive mTOR inhibitor AZD8055), the two models provided simple relationships between the concentrations of proteins of the ISN and parameters representative of cell cycle progression and cell death
A imagem de Alessandro Baricco no Brasil
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Comunicação e Expressão, Programa de Pós-Graduação em Estudos da Tradução, Florianópolis, 2013.Com a intenção de delinear o modo pelo qual o escritor italiano Alessandro Baricco se inseriu no sistema literário brasileiro e os caminhos percorridos pelos seus livros traduzidos, esta dissertação dá voz às experiências tradutórias de seus tradutores. A inserção de Bariccono Brasil tem seu início em 1997, através de uma proposição da Profa. Dra. Roberta Barni à editora Iluminuras da tradução de Oceano Mare. A partir daí, outras sete obras foram publicadas no Brasil, sendo três delas traduzidas por Roberta Barni e as outras quatro por quatro tradutores diferentes. De um lado, considera-se o tradutor como figura principal namediação entre culturas, e, de outro, se analisa a realidade desta figuradentro do sistema literário, sua invisibilidade, seus limites e o exercíciode sua profissão. A pesquisa conta, ainda, com críticas e resenhas referentes ao autor italiano publicadas em jornais consagrados no Brasil, considerando estas como parte constituinte da imagem de Baricco refletida em território nacional. Abstract : Intending to delineate the way the Italian writer Alessandro Baricco has been inserted in the Brazilian literary system and the paths his translated books have followed, this thesis gives voice to the translating experiences of his translators. Baricco's insertion in Brazil began in 1997, through a personal project of Dr. Roberta Barni, with her translation of Oceano Mare. Since then, seven other of his works have been published in Brazil, three of which were translated by Roberta Barni and the other four by four different translators. On the one hand,the translator is considered as the main figure in mediation betweencultures and, on the other, this figure's reality is analyzed within theliterary system: its invisibility, its limits and its professional practice. Criticisms and reviews of this Italian author published in well established Brazilian newspapers are also considered, with the understanding that they are part of Baricco's image reflected here
Tandem Functionalization‐Carboxylation Reactions of π‐Systems with CO 2
No full textThe tandem catalytic functionalization/carboxylation of double as well as triple carbon-carbon bonds with CO2 represent an emerging research area in synthetic organic methodology. In particular, the combination of mild reaction conditions, stoichiometric acceptor/donorless conditions (visible light photoredox catalysis) and chiral catalysts contributed to a rapid development of this intriguing research area capable of creating chemical diversity/ complexity from readily available unsaturated hydrocarbons and CO2 as a C1-buinding block. The most recent developments in the field have been collected in the present review article and organized, based on the different sets of π-systems/intermediates/reactive partners employed (i.e., nickelalactones, organo-halides) as well as synthetic strategies (i.e., visible-light photo redox catalysis)
La maturità di Alessandro Fei del Barbiere, in bilico tra Maniera e Riforma
No full textThis article studies the mature career of the Florentine painter Alessandro Fei del Barbiere (1537-1592), beginning with the rediscovery of the 'Ascension' altarpiece formerly in the Albizi Chapel in the destroyed church of San Pier Maggiore, Florence. Studying this painting and others recorded in 1584 by the biographer Raffaello Borghini, such as the two altarpieces for Santa Maria delle Grazie and the Madonna dell'Umiltà in Pistoia, the author reconstructs a body of works showing how in the 1580s Fei gradually went beyond the archaic style of his apprenticeship - he had been trained by Ridolfo del Ghirlandaio and Pierfrancesco Foschi, but was also marked by the Maniera of Vasari - evolving towards naturalism in both mimesis and pictorial handling. In Florence, his development partly parallels that of Santi di Tito and his circle, but Fei was also influenced by a probable sojourn during the early part of that decade in Rome, where he could have been inspired by Girolamo Muziano and the painters working for Pope Gregory XIII. Among other proposals, the author suggests that the artist was responsible for decorating the chancel of Fiesole Cathedral (c. 1584-1589), which consisted of an altarpiece, only rarely discussed by scholars, and a cycle of frescoes hitherto attributed to Nicodemo Ferrucci
Tra socialdemocrazie e Perestrojka. Le relazioni internazionali del Pci attraverso le carte di Alessandro Natta
No full textThis essay reconstructs the foreign policy of the Italian Communist Party during the four
years of Alessandro Natta’s secretariat (1984-1988) through largely original archival documentation,
from the Alessandro Natta Fonds of the Historical Archive of the Chamber of
Deputies. Natta’s papers are also cross-referenced with those kept in the PCI Archive at the
Gramsci Foundation. The author analyses the relationship that the PCI establishes with
Gorbachev’s Perestroika, Deng’s China, and European social democracies during the last
years of the Cold War
Volta Alessandro
No full textThe New Dictionary of Scientific Biography (extension and updating of the Dictionary of Scientific Biography) is one of the most substantial reference works in the field of the history of science. An up-to-date overview on Alessandro Volta's science with new perspectives offered by the author. Information and critical analysis is also provided on the main secondary literature produced on this main protagonist of enlightenment science after the 1976 entry "Volta Alessandro" in the Dictionary of Scientific Biography
"Muy señor nuestro Alessandro Varaldo". La ricognizione del mondo spagnolo e portoghese per riscoprire un autore italiano di successo ma dimenticato
No full textWho is Alessandro Varaldo (1876-1953)? This first analysis about what was said, adapted and translated of Varaldo’s work in the Iberian Peninsula and South America, maybe the only areas outside Italy where some traces of Italian author can be found, is a chance to go along his literary paths that overtook two temporal barriers (1900 and 1950), although it has not overtaken the oblivion’s threshold.Questa è una prima ricognizione di ciò che è stato detto, adattato e tradotto di Alessandro Varaldo (1876-1953) nella Penisola iberica e in Sud America, che si sospetta siano gli unici territori stranieri dove si riesca a ritracciare qualcosa dell’autore italiano, ed è un’occasione per ripercorrerne la traiettoria letteraria che ha superato due transenne temporali come il 1900 e il 1950 ma non quella della dimenticanza
Lean six sigma in a call centre : a case study
No full textThis paper, a case study, aims to illustrate the application of lean six sigma in a call centre of a service industry corporation. The study draws on process information and primary data from a real project. The study describes improvements in the operation of the call centre attributable to lean six sigma: increase in first-call resolution ratio, reduction in operator turnover and streamlining of processes. The introduction of lean six sigma into the call centre daily operations' management may have organizational benefits. Although lean six sigma has been extremely successful in the last two decades in the manufacturing sector, its applicability to the service sector has been a controversial topic. This study illustrates its application to a fast-growing area of the service sector, assisting companies in identifying areas of development for their call centres
First person – Alessandro Soloperto
No full textABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Alessandro Soloperto is the first author on ‘Mechano-sensitization of mammalian neuronal networks through expression of the bacterial large-conductance mechanosensitive ion channel’, published in Journal of Cell Science. Alessandro is a PhD student in the lab of Francesco Difato at Istituto Italiano di Tecnologia, Genoa, Italy, investigating the potential of targeted modulation of the neuronal Ca2+ activity via remote mechanical stimulation.</jats:p
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