561 research outputs found
Chemical and Structural Strategies to Selectively Target mTOR Kinase
No full textDysregulation of the mechanistic target of rapamycin (mTOR) pathway is implicated in cancer and neurological disorder, which identifies mTOR inhibition as promising strategy for the treatment of a variety of human disorders. First-generation mTOR inhibitors include rapamycin and its analogues (rapalogs) which act as allosteric inhibitors of TORC1. Structurally unrelated, ATP-competitive inhibitors that directly target the mTOR catalytic site inhibit both TORC1 and TORC2. Here, we review investigations of chemical scaffolds explored for the development of highly selective ATP-competitive mTOR kinase inhibitors (TORKi). Extensive medicinal chemistry campaigns allowed to overcome challenges related to structural similarity between mTOR and the phosphoinositide 3-kinase (PI3K) family. A broad region of chemical space is covered by TORKi. Here, the investigation of chemical substitutions and physicochemical properties has shed light on the compounds’ ability to cross the blood brain barrier (BBB). This work provides insights supporting the optimization of TORKi for the treatment of cancer and central nervous system disorders
Phu mkhar rdzong, un lieu de pèlerinage au Ladakh
No full textAbstract Phu mkhar rdzong, a pilgrimage site in Ladakh This paper describes the pilgrimage of Phu mkhar rdzong, a sacred place "opened" by Padmasambhava and still venerated by Buddhists, but situated in Purig (Western Ladakh), a region inhabited mostly by Ladakhi Muslims. The description of the place given in "the new explanation of the holy site" (gnas bshadgso ma), written in 1993 by rTogs Jdan Rin po che, the head of the 'Bri gung pa school in Ladakh who had a long career in Ladakhi politics, is compared with the discourse and behaviour of lay pilgrims. On the basis of this study, the author questions the revitalisation of the pilgrimage and, more generally, the awakening of "national" consciousness among Ladakhi Buddhists along religious / communal lines.Dollfus Pascale. Phu mkhar rdzong, un lieu de pèlerinage au Ladakh. In: Bulletin de l'Ecole française d'Extrême-Orient. Tome 86, 1999. pp. 33-64
El boom latinoamericano y la movilidad de los polisistemas: una discusión a la propuesta de Pascale Casanova
No full textThis article attempts to establish a theoretical discussion before its application. Its starting point is Pascale Casanova’s thesis about the universalism of French literature, which will later be contested. Using comparative studies, the article will seek to challenge the static and stable concept of the world system that was developed by the French author. To achieve this, the proposed dialogue will explore Even-Zohar’s theory of polysytems, along with Françoise Perus´s ideas about the Latin American reality of heterogeneity being established from birth. This dialectical discussion will then be substantiated through a brief review of the circumstances and consequences of the Latin American boom, which was born in the ‘60s and ‘70s.El presente artículo, cuyo objetivo es establecer una discusión teórica antes que aplicada, tiene como punto de partida la tesis de Pascale Casanova sobre el universalismo de la literatura francesa, pero con la finalidad de controvertirla. Desde la perspectiva de los estudios comparados, se pretende cuestionar aquí el estático y estable concepto de sistema mundial desarrollado por la autora francesa. Con el fin de lograr dicho objetivo, se establece un diálogo tanto con la teoría de los polisistemas de Even-Zohar como con las ideas de Françoise Perus sobre la realidad latinoamericana en cuanto marcada por la heterogeneidad desde su nacimiento. Tal recorrido dialéctico se consuma y concreta a través de una breve revisión de las circunstancias y consecuencias del boom latinoamericano nacido en los 60 y 70
« Cet obscur objet du désir » : l’objet de collection dans la fiction fitzgeraldienne
No full textThis paper seeks to demonstrate both the strategic and the heuristic role of collections in Fitzgerald's fiction. While they reveal the heroes' (sexual) desire, they also expose a double system of reference which is both mimetic and reflexive. They are thus symptomatic objects exhibiting a close link not only between desire and fiction but also between collector and author throughout the novelist's work.Antolin Pascale. « Cet obscur objet du désir » : l’objet de collection dans la fiction fitzgeraldienne. In: Revue Française d'Etudes Américaines, N°78, octobre 1998. L'édition américaine en mouvement. pp. 112-122
Conservation ou rénovation ? Transitions de la politique culturelle
No full textConservation or Renovation ? Transitions in the Arts Policy.
Pascale Laborier [111-132].
The transfer of the West German federal system in the arts sector in ex-GDR has faced the institutional and political actors with numerous difficultes related to both the destruction of the old system and the construction of a role of law and an efficient political system. A series of interviews with actors working in regional and municipal departments for the arts, theatre, museum and cabaret directors, artists and MP's allows the author to capture the diverse representations that these persons in charge of the administrative reconstruction have of a legitimate cultural action. In terms of its modalities and content. An analysis using the notion of repertoire allows to test both the fiction of a simple return to the German «cultural nation» and the simplistic interpretation of the rational transfer of one system to another.Conservation ou rénovation ? Transitions de la politique culturelle.
Pascale Laborier [111-132].
Le transfert du système fédéraliste ouest-allemand dans le secteur «culturel» en ex-RDA a confronté les acteurs institutionnels et politiques à de nombreuses difficultés qui résident, d'une part, dans la destruction de l'ancien système et d'autre part, dans la construction d'un État de droit et d'un système politique efficace. Une série d'entretiens menés dans les nouveaux Länder en 1992 auprès de responsables des nouveaux ministères régionaux et des services municipaux de la culture, de directeurs de musée, de théâtre ou de cabaret, d'artistes, de députés, etc. permet ici de saisir les diverses représentations que ces acteurs (Allemands de l'Ouest et de l'Est) de la reconstruction administrative se faisaient d'une action culturelle légitime, non seulement quant aux modalités de l'intervention mais aussi quant à ses contenus afin d'exposer les mécanismes par lesquels un système fédéraliste a été «transféré» sur les ruines d'un système centralisé. L'analyse en termes de répertoires permet d'éprouver tant la fiction du simple retour à la «nation culturelle» allemande que l'interprétation simplificatrice du transfert rationnel d'un système à l'autre.Laborier Pascale. Conservation ou rénovation ? Transitions de la politique culturelle. In: Politix, vol. 9, n°33, Premier trimestre 1996. Allemagnes, année zéro, sous la direction de Patrick Hassenteufel et Yves Déloye. pp. 111-132
Estratégias acadêmicas como alternativa de avaliação de desempenho docente: o caso da Faculdade Estácio de Sá de Santa Catarina
No full textTese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-Graduação em Engenharia de ProduçãoA avaliação assume a partir da década de 90 um papel de destaque no contexto das Instituições de Ensino Superior, tanto por proporcionar mais informações para gestão e qualificação dos serviços educacionais prestados à sociedade brasileira, quanto para embasamento das políticas governamentais que regem a sua expansão. Assim, o presente trabalho tem por objetivo geral apresentar um modelo de avaliação de desempenho docente, a partir das estratégias acadêmicas constantes nos Projetos Pedagógicos dos cursos de graduação da Faculdade Estácio de Sá de Santa Catarina. Num segundo momento, a pesquisa faz uma análise da evolução histórica do ensino superior no Brasil, com o objetivo de evidenciar o ambiente competitivo que bem caracteriza o mercado da educação neste nível de ensino. Neste contexto, procura-se evidenciar a importância de novos instrumentos de gestão para o sucesso das instituições de ensino superior, principalmente para uma eficaz administração do corpo docente nas estratégias delineadas para consecução dos objetivos organizacionais.Assim sendo, a pesquisa evidencia os principais modelos de avaliação no contexto da educação superior, a importância da avaliação de desempenho e das estratégias para consecução dos objetivos e alcance dos resultados planejados pela organização, com vistas à proposição de um modelo de avaliação com base no desempenho docente nas estratégias acadêmicas em Instituições de Ensino Superior. A pesquisa em pauta é do tipo exploratória, descritiva e avaliativa. O método utilizado é o histórico interpretativo e o modo de investigação o estudo de caso. Os dados foram coletados através de entrevistas do tipo não-estruturadas, análise documental, observação e questionários. O tratamento dos dados se dá de forma qualitativa e quantitativa.O modelo de avaliação com base no desempenho docente nas estratégias acadêmicas é validado no Curso de Administração e Ênfases da Faculdade Estácio de Sá de SC, sendo importante frisar que permite analisar com detalhes a atuação de cada professor no alcance dos objetivos traçados pela Instituição, isto dentro dos parâmetros de gestão estabelecidos pelos administradores acadêmicos. Assim sendo, evidencia tanto os pontos vulneráveis que merecem maior atenção dos gestores acadêmicos, quanto àqueles que estão no caminho certo e precisam tão somente ser mantidos e aperfeiçoados. Portanto, o modelo proposto configura-se como uma nova e importante ferramenta de gestão para instituições de ensino superior, pois permite ao administrador maximizar a eficácia das organizações neste nível de ensino
Inventaire des manuscrits du Pseudo-Phocylide
No full textA scholarly text, the Sentences of the Pseudo-Phocylides exist in a large number of manuscripts, both medieval and later. As a preliminary to a new critical edition, the author has drawn up for the first time an exhaustive list of nearly 160 copies, dating from the tenth to the nineteenth centuries, which have been conserved in the main libraries of Europe and the Near-East.Texte scolaire, les Sentences du Pseudo-Phocylide figurent dans un nombre considérable de manuscrits, médiévaux ou plus tardifs. En préliminaire à une nouvelle édition critique, l'auteur dresse pour la première fois un inventaire exhaustif de près de 160 copies, s'échelonnant du Xe au XIXe siècle, et conservées dans les principales bibliothèques d'Europe et du Proche-Orient.Derron Pascale. Inventaire des manuscrits du Pseudo-Phocylide. In: Revue d'histoire des textes, bulletin n°10 (1980), 1982. pp. 237-247
L'Académie royale des sciences et les grandes commissions d'enquête et d'expertise à la fin de l'Ancien Régime
No full textPascale Mafarette-Dayries, The Royal Academy of Sciences and problems of public interest at the end of the Ancien Régime : Commissions of Inquiry and Expertise
Created by Colbert, the Royal Academy of Sciences remained intimately connected to the state and regularly served in pursuit of its utilitarian goals. Preparing maps and plans, as well as examining memoirs in order to grant permission for publication, the Academy was at the same time expert, judge, investigator and the author of scientific projects. During the last years of the Ancien Régime, it was more than ever solicited by the government, which used the Academy's reports to support its many goals. Within the Academy, major commissions of inquiry and expertise were charged with familiarizing themselves with and reporting on work which went beyond the scope of its traditional sphere of competence. The coincidence of the Baron de Breteuil's and Lavoisier's aspirations undoubtedly favored the emergence of these new structures for the work. The Academy of Sciences progressively became an indispensable auxiliary of the state in its task of informing itself with respect to questions of public interest. In parallel, the Academy imposed its own orientation with respect to new scientific and technical issues. The Revolutionary assemblies were not to be fooled by the Academy.Création de Colbert, l'Académie royale des sciences reste intimement liée à l'État dont elle sert régulièrement les visées utilitaires. Établissement de cartes et de plans, examen de mémoires pour la délivrance des privilèges, l'Académie est tout à la fois expert, juge, enquêteur et auteur de projets scientifiques. Au cours des dernières années de l'Ancien Régime, elle est plus que jamais sollicitée par le gouvernement, qui s'appuie sur ses rapports pour soutenir ses multiples ambitions. En son sein, de grandes commissions d'enquête et d'expertise sont chargées de connaître et de rendre compte de travaux débordant le cadre de ses compétences traditionnelles. La rencontre des aspirations respectives du baron de Breteuil et de Lavoisier a incontestablement favorisé l'émergence de ces nouvelles structures de travail. L'Académie des sciences devient progressivement l'auxiliaire indispensable de l'État pour connaître des questions d'intérêt public. Parallèlement, elle impose ses orientations face aux nouveaux enjeux scientifiques et techniques. Les assemblées révolutionnaires ne s'y tromperont pas.Mafarette-Dayries Pascale. L'Académie royale des sciences et les grandes commissions d'enquête et d'expertise à la fin de l'Ancien Régime. In: Annales historiques de la Révolution française, n°320, 2000. pp. 121-135
El boom latinoamericano y la movilidad de los polisistemas : una discusión a la propuesta de Pascale Casanova
No full textEl presente artículo, cuyo objetivo es establecer una discusión teórica antes que aplicada, tiene como punto de partida la tesis de Pascale Casanova sobre el universalismo de la literatura francesa, pero con la finalidad de controvertirla. Desde la perspectiva de los estudios comparados, se pretende cuestionar aquí el estático y estable concepto de sistema mundial desarrollado por la autora francesa. Con el fin de lograr dicho objetivo, se establece un diálogo tanto con la teoría de los polisistemas de Even-Zohar como con las ideas de Françoise Perus sobre la realidad latinoamericana en cuanto marcada por la heterogeneidad desde su nacimiento. Tal recorrido dialéctico se consuma y concreta a través de una breve revisión de las circunstancias y consecuencias del boom latinoamericano nacido en los 60 y 70.This article attempts to establish a theoretical discussion before its application. Its starting point is Pascale Casanova's thesis about the universalism of French literature, which will later be contested. Using comparative studies, the article will seek to challenge the static and stable concept of the world system that was developed by the French author. To achieve this, the proposed dialogue will explore Even-Zohar's theory of polysytems, along with Françoise Perus's ideas about the Latin American reality of heterogeneity being established from birth. This dialectical discussion will then be substantiated through a brief review of the circumstances and consequences of the Latin American boom, which was born in the '60s and '70s
Letture di Temistio tra il XIV e il XV secolo
No full textThis paper aims to complete the survey of all extant witnesses of Themi- stius, orationes IV-V-VII-IX-X (a corpusculum of late antique origin), by means of analysis and collation of the text transmitted by four mss. which contain excerpts or single speeches: namely mss. Heidelberg, Universitätsbibliothek, Pal. gr. 129 (K); Torino, Biblioteca Nazionale Universitaria, B.V.33 (T); Firenze, Biblioteca Riccardiana, 12 (E); Paris, Bibliothèque nationale de France, gr. 2967 (c). A brief description of the manuscripts is provided and their relationships with other wit- nesses of Themistius’ speeches are established; hence the four mss. find place in the stemma codicum drawn up by the author in a previous work. Finally, the re- sults of new research about some important witnesses of Themistius’ speeches are presented: in particular, most of the manuscripts appear to have beeen copied and studied during the Palaeologan Period (XIII-XIV century), between Thessaloniki and Constantinople
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