3,068 research outputs found
Rozpor ako východisko, láska ako smer u Simone Weilovej (Contradiction as base, Love as direction in writings of Simone Weil)
No full textArticle is explaining contradiction and love, Simone Weil‘s essential terms of hermeneutics of human Being. It introduces close relation of these terms with her understanding of God as well as with her overall concept of religion. Author also mentions Simone Weil‘s inspirations with philosophical and spiritual concepts of the East
p38α, the β-catenin chromatin associated kinase, as promising target in colorectal cancer stem cells for personalized therapy
No full textColorectal cancer (CRC) is the third most frequent malignancy, but the second cause of death for tumor in the western population. Only 14% of patients with advanced and metastatic disease survive five years from diagnosis. Recently, it has been shown that tumor relapse and chemoresistance depend on a small population of cells, called cancer stem cells (CSCs). Current evidence indicates that the Wnt cascade is the main driver in controlling CSC fate; the key player in this pathway is β-catenin, a cytoplasmic protein whose stability is regulated by the so-called “destruction complex”. During carcinogenesis, the increasing amount of β-catenin resulting from APC inactivation translocates into the nucleus, causing the transcriptional activation of several mitogenic genes, including c-Myc. c-Myc is one of the most important factors involved in CRC initiation and progression; indeed, it functions as a link connecting malignancy with stemness. During colorectal carcinogenesis, c-Myc is maintained upregulated through β-catenin-mediated transcriptional activation and ERK-mediated post-translational stabilization. Our data showed that p38α, a kinase involved in CRC metabolism and survival, contributes to both mechanisms. Previous reports in other tissues provided evidence that Wnt3a can activate p38, and the p38 pathway feeds into the canonical Wnt/β-catenin pathway at least at the level of GSK3β. Our findings also highlighted that CRC cells and colorectal cancer stem cells (CRC-SCs) have higher levels of activated p38 than their normal counterparts, and experiments using kinase-specific inhibitors revealed that these cells are “addicted” to p38 activity. Importantly, we found that p38α co-immunoprecipitates with β-catenin in both normal and cancer cells; however, these proteins are confined to the cytoplasm in colonocytes, while they significantly occupy discrete nuclear regions in CRC cells, CRC-SCs, and in vivo models. These data were further corroborated by the inhibitory effect of p38α blockade on several β-catenin-responsive genes (i.e. c-Myc, cyclin D1/2, survivin, and others). This functional interaction was further characterized by chromatin immunoprecipitation experiments, which demonstrated that p38α is a chromatin-associated β-catenin kinase required for the transcriptional induction of several Wnt target genes, including c-Myc. Additionally, we demonstrated that p38α, like ERK, stabilizes c-Myc protein levels by preventing its ubiquitination. The finding that the phenotypes arising after APC loss in the intestine are fully dependent on c-Myc target gene expression suggests that c-Myc inhibition may be a good target for chemoprevention in CRC. These considerations underline the relevance of molecular profiling and preclinical investigation in order to achieve more efficient and accurate therapies. Indeed, our study identifies p38α as a promising therapeutic target acting directly on c-Myc and CRC-SCs, which are thought to be responsible for tumor proliferation, metastatic dissemination, and chemoresistance
Consolidamenti e stimoli fiscali nell’UE: un’analisi empirica
No full textIl volume raccoglie i risultati di una ricerca del CREI di Roma Tre, su "Legge di Stabilità e politica economica europea" svolta da Lilia Cavallari, Stefano D'Addona, Rama Dasi Mariani, Francesco Forte, Marilena Giannetti, Valerio Intraligi, Filippo Lepore, Cosimo Magazzino, Olga Marzovilla, Marco Mele, Paolo Naticchioni, Gian Cesare Romagnoli, Simone Romano e Gaetana Trupiano. La Legge di stabilità per il 2015 segnala un cambio di stagione importante, anche se non è risolutiva, di per sé, in termini di spinta alla crescita e alla riduzione del debito pubblico. La novità sostanziale è data da una riduzione consistente del cuneo fiscale, come parte di una nuova politica industriale basata soprattutto sulle riforme strutturali, che il Paese attende da anni. Essa si accompagna al Jobs Act da cui pure si attende una ripresa della crescita.
Le risorse di gettito aggiuntive prodotte dalla più rapida crescita saranno destinate ad addolcire l'onere dell'aggiustamento fiscale per famiglie e imprese. La Legge di Stabilità trova un soddisfacente punto di incontro tra austerity e crescita e si collega alle politiche di exit strategy dalla crisi economica che beneficeranno della riduzione degli spread attesa anche dal Quantitative Easing.
Con questo scopo, la ricerca ha guardato agli effetti delle politiche fiscale e monetaria europee e alle tendenze del mercato del lavoro in presenza di cambiamento tecnologico e di immigrazione. L'approccio seguito dal governo Renzi è stato quello di impegnarsi sulle riforme istituzionali e strutturali richieste dalla nuova governance europea piuttosto che invocare l'unione politica, per la quale mancano ancora i presupposti, come panacea del debito pubblico. In questa temperie storica, la domanda di unione politica è maggiore dell'offerta e ciò costringe i paesi che la domandano a pagare prezzi più alti in termini di quadro macroeconomico. L'auspicio espresso dalla ricerca effettuata dal CREI nell'anno precedente, che il nuovo governo potesse trarre utili elementi di riflessione dai suoi risultati, anche sul profilo redistributivo di un welfare meno universalistico, ha trovato un riscontro
“I beg you to tell me what has become of Djamila”: The Political Mobilization of Simone de Beauvoir’s Readers During the Boupacha Affair
No full textBy Sophia Millman This is a condensed version of a Masters thesis dedicated to the political mobilization of Simone de Beauvoir’s readers. The citations from the letters were translated from French by the author. *** On June 2, 1960, the French government ordered all copies of the daily Algiers edition of Le Monde seized and destroyed to suppress the publication of Simone de Beauvoir’s article “Pour Djamila Boupacha.” Beauvoir, a self-professed “woman of letters”, not “of action[1]”, and one ..
A. Lepore I datori di lavoro
No full textL'inquadramento previdenziale del datore di lavoro rende edotti dei doveri contributivi del datore di lavor
Smooth Lasso Estimator for the Function-on-Function Linear Regression Model
No full textA new estimator, named S-LASSO, is proposed for the coefficient function of
the Function-on-Function linear regression model. The S-LASSO estimator is
shown to be able to increase the interpretability of the model, by better
locating regions where the coefficient function is zero, and to smoothly
estimate non-zero values of the coefficient function. The sparsity of the
estimator is ensured by a \textit{functional LASSO penalty}, which pointwise
shrinks toward zero the coefficient function, while the smoothness is provided
by two roughness penalties that penalize the curvature of the final estimator.
The resulting estimator is proved to be estimation and pointwise sign
consistent. Via an extensive Monte Carlo simulation study, the estimation and
predictive performance of the S-LASSO estimator are shown to be better than (or
at worst comparable with) competing estimators already presented in the
literature before. Practical advantages of the S-LASSO estimator are
illustrated through the analysis of the \textit{Canadian weather},
\textit{Swedish mortality} and \textit{ship CO\textsubscript{2} emission data}.
The S-LASSO method is implemented in the \textsf{R} package \textsf{slasso},
openly available online on CRAN.Comment: In press on Computational Statistics & Data Analysi
Il controllo nelle società dei servizi pubblici locali: una proposta di inquadramento metodologico
No full textA comparative study of form and theology in the works of Flannery O'Connor and Simone Weil
No full textIn this comparative study of the form and theology of Flannery O'Connor and Simone Weil I interrogate how Weil's philosophical writings and her theology illuminate O'Connor's use of both narrative and non-fictional forms, and her Catholicism. The Introduction analyses how Weil's concept of superposed reading provides a new method of approaching both O'Connor, her writings, and O'Connor
studies, and focuses on how such apparently different women interconnect. Chapter One explores how both Weil and O'Connor attempt to write their theologies on the
souls of their readers yet are each subject to constraints imposed by form. Weil's concept of locating equilibrium between incommensurates is discussed, and her
distinctively philosophical approach to fictions and fictionality is used to investigate O'Connor's notion of prophetic fictions and the writer's role. Chapter Two assesses how both writers revivify Christian paradoxes. Weil's monstrous concept of affiiction, and O'Connor's use of the grotesque genre to jolt secular man into an
awareness of the sacred are scrutinised. Chapter Three studies how both writers consider an encounter between God and man is possible through the action of grace. My Conclusion interrogates how Weil's work can deepen our understanding of O'Connor's writings, and examines how successful O'Connor is at realising a truly
Christian literature. I conclude that despite being a writer of powerful fictions, O'Connor can not be totally successful in her mission as writer-prophet because
ultimately fiction escapes orthodoxy
Colorectal Cancer Chemoprevention: A Dream Coming True?
No full textColorectal cancer (CRC) is one of the deadliest forms of cancer worldwide. CRC development occurs mainly through the adenoma-carcinoma sequence, which can last decades, giving the opportunity for primary prevention and early detection. CRC prevention involves different approaches, ranging from fecal occult blood testing and colonoscopy screening to chemoprevention. In this review, we discuss the main findings gathered in the field of CRC chemoprevention, focusing on different target populations and on various precancerous lesions that can be used as efficacy evaluation endpoints for chemoprevention. The ideal chemopreventive agent should be well tolerated and easy to administer, with low side effects. Moreover, it should be readily available at a low cost. These properties are crucial because these compounds are meant to be used for a long time in populations with different CRC risk profiles. Several agents have been investigated so far, some of which are currently used in clinical practice. However, further investigation is needed to devise a comprehensive and effective chemoprevention strategy for CRC
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