7,893 research outputs found
The PNPLA3 I148M variant and chronic liver disease: When a genetic mutation meets nutrients
No full textAbstractThe isoleucine to methionine substitution at position 148 in the patatin-like phospholipase domain containing 3 protein (PNPLA3; I148M variant, rs738409) is associated with liver fat accumulation and an increased risk of chronic liver disease ranging from hepatitis to hepatocellular carcinoma. This review discusses the interaction between the PNPLA3 I148M variant and obesity/intake of specific nutrients in determining the susceptibility to liver disease. We present the results of several studies showing that obesity or alcohol abuse enhances the effect of the PNPLA3 I148M variant on the liver. We also show that specific nutrients interact with the PNPLA3 I148M variant in modulating liver disease susceptibility
Michelstaedter Carlo
No full textPressoché tutti gli scritti di Carlo Michelstaedter furono pubblicati solo dopo il suo sucidio, prima dagli amici V. Arangio-Ruiz e G. Chiavacci e, più recentemente, in molte altre edizioni che l’hanno reso uno dei filosofi italiani più letti e studiati del primo Novecento. La sua riflessione si radica in un contesto mitteleuropeo attraversato da crisi esistenziali e influenze filosofiche che spaziano da Parmenide e Eraclito fino a Ibsen e Nietzsche. Egli critica la “rettorica”, che rappresenta la sottomissione agli interessi egoistici e alle strutture di potere; alla retorica egli contrappone il “benificio”, inteso come apertura disinteressata all’altro, e la “persuasione” quale aspetto soggettivo di colui che agisce il beneficio: la carica emotiva che lo abita. Figure esemplari di persuasione sono in Michelstaedter non solo esponenti del pensiero filosofico e artistico, ma anche grandi riferimenti religiosi come l’autore dell’Ecclesiaste e Cristo.
Parole chiave: Carlo Michelstaedter; persuasione e rettorica; beneficio; Ecclesiaste; Cristo
Almost all of Carlo Michelstaedter’s writings were published only after his suicide, first by friends V. Arangio-Ruiz and G. Chiavacci, and more recently in many other editions that have made him one of the most read and studied Italian philosophers of the early twentieth century. His reflection is rooted in a Central European context marked by existential crises and philosophical influences ranging from Parmenides and Heraclitus to Ibsen and Nietzsche. He criticizes ‘rhetoric,’ which represents submission to selfish interests and power structures; against rhetoric, he opposes ‘benefit,’ understood as a disinterested openness to the other, and ‘persuasion’ as the subjective aspect of the one who acts for the benefit: the emotional charge that inhabits him. Exemplary figures of persuasion in Michelstaedter are not only representatives of philosophical and artistic thought but also great religious references such as the author of Ecclesiastes and Christ.
Keywords: Carlo Michelstaedter; persuasion and rhetoric; benefit; Ecclesiastes; Chris
Enhancing quasi-Monte Carlo methods via delta dimension and directional control technique
No full textMolecular genetics of patatin-like phospholipase domain-containing 3 and chronic liver disease
No full textChronic liver disease is a major health burden worldwide. Major determinants of this condition are viral infections, alcohol abuse and obesity. Genetic background modulates the effect of damaging agents on the liver. The genetic variant rs738409 in the patatin-like phospholipase domain-containing 3 (PNPLA3) gene associates with increased susceptibility to the entire spectrum of chronic liver disease, and in particular with non-alcoholic fatty liver disease. The variant results in an isoleucine to methionine substitution at position 148 (I148M) of the amino acidic sequence and was first associated with increased hepatocyte fat content. Despite the strength of the genetic association, the mechanisms causing liver fat accumulation and hepatocyte damage are not yet understood.
In this thesis, we tested the following hypotheses: 1) PNPLA3 is involved in hepatic very low density lipoprotein secretion 2) the protein acts as a glycerolipid hydrolase and the 148M mutation is a loss of function 3) PNPLA3 has a specific role in retinol metabolism in hepatic stellate cells. We tested the first hypothesis measuring VLDL secretion in a cohort of 55 individuals genotyped for the I148M variant and we found that carriers of the 148M allele secret less VLDL for a given amount of liver fat. We confirmed this result in vitro by measuring APOB secretion in cell lines stably overexpressing the 148I or the 148M PNPLA3. We tested the second hypothesis performing enzymatic activity assays using purified 148I and 148M recombinant proteins. The wild type protein had glycerolipid hydrolase activity and the 148M mutation induced a loss of function. Finally, we tested the third hypothesis assessing the effect of PNPLA3 up- and down-regulation on hepatic stellate cell retinyl palmitate content and retinol release. We found that PNPLA3 insulin–mediated up-regulation induces retinol release from hepatic stellate cells and that this effect is abolished by PNPLA3 silencing. We confirmed this finding by looking at human circulating levels of RBP4, a reliable marker of retinol plasma levels, in 146 individuals genotyped for the I148M variant. We found carriers of the M allele to have lower RBP4 plasma levels, confirming the role of PNPLA3 in retinol metabolism.
In conclusion, we identified two possible mechanisms underlying the susceptibility to chronic liver disease in carriers of the PNPLA3 mutation: 1) reduced intracellular triglyceride mobilization leading to hepatocyte damage 2) impaired hepatic stellate cell retinol metabolism causing abnormal response of hepatocytes to damaging agents
Carlo Vallini: restless spirit between dannunzianism and crepuscolarism
No full textopenIl progetto di tesi riguarda una ricerca bibliografica da me condotta sull'iter poetico del poeta, drammaturgo e docente Carlo Vallini, personalità vissuta a cavallo fra XIX e XX secolo. Tale figura è stata letterariamente influenzata da altre figure italiane di grande spicco, quali, fra i principali, Giovanni Pascoli e Gabriele D'Annunzio, incuneandosi però anche nella stagione poetica contrassegnata dal movimento del crepuscolarismo (in particolare, stretto legame con Guido Gozzano). Il taglio della mia ricerca verte quindi su un'analisi delle opere principali di Carlo Vallini, maggiormente esprimenti la sua personalità, dando voce ad un autore in bilico fra dannunzianesimo e crepuscolarismo.The thesis project concerns a bibliographic research I conducted on the poetic career of poet, playwright and teacher Carlo Vallini, a personality who lived at the turn of the 19th and 20th centuries. This figure was literarily influenced by other prominent Italian figures, such as, among the main ones, Giovanni Pascoli and Gabriele D'Annunzio, wedging himself, however, also into the poetic season marked by the Crepuscolarismo movement (in particular, close ties with Guido Gozzano). Therefore, the focus of my research is on an analysis of Carlo Vallini's major works, most expressive of his personality, giving voice to an author poised between D'Annunzianism and Crepuscolarism
Carlo Ferdinando Russo, Aristophanes, An Author for the Stage.
No full textByl Simon. Carlo Ferdinando Russo, Aristophanes, An Author for the Stage.. In: L'antiquité classique, Tome 65, 1996. p. 296
Carlo Ferdinando Russo, Aristophanes, An Author for the Stage.
No full textByl Simon. Carlo Ferdinando Russo, Aristophanes, An Author for the Stage.. In: L'antiquité classique, Tome 65, 1996. p. 296
Valuation of R&D Sequential Exchange Options using Monte Carlo approach
No full textThis article describes a methodology for evaluating R&D investment projects using Monte Carlomethods. R&D projects generally involves multiple phases with or without overlapping. R&D investments are made often in a phased manner, with the commencement of subsequent phase being dependent on the successful completion of the preceding phase, it is known as sequential investment. Moreover, each stage creates an opportunity (option) for subsequent investment. Therefore, R&D projects can be considered as ‘Compound Options' in which investments present uncertainty both in the gross project value and in costs. It is possible to use exchange options to value the R&D investment opportunities. In this paper, we propose to value the European and American Real Compound Exchange options through Monte Carlo simulation. We also provide a set of numerical experiments to provide evidence for the accuracy of the proposed methodology.Pseudo Compound American Exchange option; R&D;Monte Carlo Methods.
The Fan and the Idol: Re-tracing Authorship in “The Author of Beltraffio”
No full textThis article is an investigation of the theme of authorship in Henry James’s tale “The author of Beltraffio.” Written at a crucial stage of James’s career, this tale stands at the crossroads between James’s high realism, his uneasy flirting with aestheticism, and his more experimental narrative turns. The article argues that in this story authorship is step by step not only mobilized, but also vampirized and dispossessed by the narrator, who exchanges the intimacy with the author and his individuality for commodities to be consumed. Authorship, Martinez contends, is figured in the tale as the result of a social discourse, where the veneration of the narrator for the “author of Beltraffio” borders on the relationship between “fan” and “idol.” Such a gesture is located within the broader cultural concerns James was dealing with at the time: the establishment of literary realism in America; the reconfiguration of the relation between private and public experience; the emergence of a mass readership; and a growing bifurcation between the mutually constituting high-brow and low-brow cultural spheres
The Fan and the Idol: Re-tracing Authorship in “The Author of Beltraffio”
No full textThis article is an investigation of the theme of authorship in Henry James’s tale “The author of Beltraffio.” Written at a crucial stage of James’s career, this tale stands at the crossroads between James’s high realism, his uneasy flirting with aestheticism, and his more experimental narrative turns. The article argues that in this story authorship is step by step not only mobilized, but also vampirized and dispossessed by the narrator, who exchanges the intimacy with the author and his individuality for commodities to be consumed. Authorship, Martinez contends, is figured in the tale as the result of a social discourse, where the veneration of the narrator for the “author of Beltraffio” borders on the relationship between “fan” and “idol.” Such a gesture is located within the broader cultural concerns James was dealing with at the time: the establishment of literary realism in America; the reconfiguration of the relation between private and public experience; the emergence of a mass readership; and a growing bifurcation between the mutually constituting high-brow and low-brow cultural spheres
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