Philosophy and Exegesis in al-Fârâbî, Averroes, and Maimonides

À plusieurs égards, il est vrai d’avancer que Maïmonide et Averroès poursuivent le même projet philosophique et religieux. D’autant plus que tous deux ont été décrits comme des disciples d’al-Fârâbî, le fondateur de l’école de l’aristotélisme arabe (falsafa). Cependant, à première vue, leur oeuvre ne pouvait pas être moins ressemblante : Averroès n’a écrit presque exclusivement que des commentaires sur Aristote, cependant que Maïmonide n’est l’auteur d’aucune oeuvre qui appartienne à un genre philosophique dans le sens strict. Il est, d’un autre côté, un commentateur distingué lui aussi — sauf qu’il n’explique pas Aristote, mais commente et met de l’ordre dans la Loi de Moïse. La question principale dont je traite dans cet article, est celle de savoir si ce rapport tellement différent à la philosophie et à l’exégèse chez Averroès et Maïmonide peut être compris comme deux façons d’implémenter le cadre conceptuel établi par al-Fârâbî. Je commence par examiner le projet d’al-Fârâbî, que j’essaie d’expliquer par deux objectifs : reprendre et continuer le projet de la philosophie antique et définir sa place dans une société, dans laquelle l’autorité de la Loi divine n’est pas mise en question. Ensuite, je montre que, tandis que l’oeuvre d’Averroès peut être comprise, dans l’ensemble, comme une continuation du projet d’al-Fârâbî, cela n’est pas vrai de la même façon pour l’oeuvre de Maïmonide qui en partie transforme al-Fârâbî de manière créative et en partie utilise des prémisses dont on ne trouvera pas la source en al-Fârâbî. La position de Maïmonide en ce qui concerne la philosophie et l’exégèse se distingue significativement de la position habituelle adoptée par les falâsifa, ce qui a eu des conséquences importantes pour la philosophie juive médiévale après Maïmonide.Maimonides and Averroes shared in many respects a philosophical-religious outlook and have been described as disciples of al-Fârâbî, the founder of the school of Arabic Aristotelianism (falsafa). At first view, however, their legacy could hardly be more different : while Averroes wrote almost only commentaries on Aristotle, Maimonides did not write a single work that, strictly speaking, falls into a traditional philosophical genre. He is, on the other hand, a prominent commentator as well — only that instead of explicating Aristotle, he comments on the Law of Moses. The main question I address in this paper is whether this strikingly different relation to philosophy and exegesis in Averroes and Maimonides can be explained as two ways of implementing a conceptual framework established by al-Fârâbî. I first examine al-Fârâbî’s project, which I suggest is determined by a twofold task : to take up and continue the project of ancient philosophy and to define its place in a society in which the authority of the divine Law is undisputed. Then I argue that while Averroes’ work can on the whole be understood as continuing al-Fârâbî’s project, this is only in a qualified way true for Maimonides who in part creatively transforms al-Fârâbî and in part relies on premises that can clearly not be derived from al-Fârâbî. Maimonides’ position on philosophy and exegesis is in important respects different from the standard position of the falâsifa — and this had far-reaching implications for later medieval Jewish philosophy

A filosofia em um mundo dividido: Beatrice Wilford entrevista Carlos Fraenkel

Nesta entrevista, Carlos Fraenkel recomenda aqueles que considera os melhores livros de filosofia para um mundo dividido.  Philosophy in a divided world: Beatrice Wilford interviews Carlos Frankel - Abstract: In this interview, Carlos Fraenkel recommends the best books on Philosophy in a divided world. (Originally published in Five Books: http://fivebooks.com/interview/carlos-fraenkel-on-philosophy-in-a-divided-world/,  

Electrostatic hot spot on DNA-binding domains mediates phosphate desolvation and the pre-organization of specificity determinant side chains

A major obstacle towards elucidating the molecular basis of transcriptional regulation is the lack of a detailed understanding of the interplay between non-specific and specific protein–DNA interactions. Based on molecular dynamics simulations of C2H2 zinc fingers (ZFs) and engrailed homeodomain transcription factors (TFs), we show that each of the studied DNA-binding domains has a set of highly constrained side chains in preset configurations ready to form hydrogen bonds with the DNA backbone. Interestingly, those domains that bury their recognition helix into the major groove are found to have an electrostatic hot spot for Cl− ions located on the same binding cavity as the most buried DNA phosphate. The spot is characterized by three protein hydrogen bond donors, often including two basic side chains. If bound, Cl− ions, likely mimicking phosphates, steer side chains that end up forming specific contacts with bases into bound-like conformations. These findings are consistent with a multi-step DNA-binding mechanism in which a pre-organized set of TF side chains assist in the desolvation of phosphates into well defined sites, prompting the re-organization of specificity determining side chains into conformations suitable for the recognition of their cognate sequence

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Introduction: Debates on Experience and Empiricism in Nineteenth Century France

The lasting effects of the debate over canon-formation during the 1980s affected the whole field of Humanities, which became increasingly engaged in interrogating the origin and function of the Western canon (Gorak 1991; Searle 1990). In philosophy, a great deal of criticism was, as a result, directed at the traditional narrative of seventeenth-and eighteenth-century philosophies—a critique informed by postcolonialism (Park 2013) as well as feminist historiography (Shapiro 2016). D. F. Norton (1981), L. Loeb (1981) and many others1 attempted to demonstrate the weaknesses of the tripartite division between rationalism, empiricism and critical philosophy.2 As time went on, symptoms of dissatisfaction with what has been called the “standard narrative” ( Vanzo 2013) and the “epistemological par-adigm” (Haakonssen 2004, 2006) only increased. Indeed, at present, a consensus has been reached that the narrative of the antagonism between “Continental rationalism” and “British empiricism”, and the consequent Aufhebung provided by “German critical philosophy,” has been unable to make sense of the complexity, variety and dynamics of early modern.Fil: Antoine-Mahut, Delphine. Ecole Normale Supérieure; FranciaFil: Manzo, Silvia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones en Humanidades y Ciencias Sociales. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación. Instituto de Investigaciones en Humanidades y Ciencias Sociales; Argentin

A filosofia em um mundo dividido: Beatrice Wilford entrevista Carlos Fraenkel

Nesta entrevista, Carlos Fraenkel recomenda aqueles que considera os melhores livros de filosofia para um mundo dividido.  Philosophy in a divided world: Beatrice Wilford interviews Carlos Frankel - Abstract: In this interview, Carlos Fraenkel recommends the best books on Philosophy in a divided world. (Originally published in Five Books: http://fivebooks.com/interview/carlos-fraenkel-on-philosophy-in-a-divided-world/,