Universidad Jean-Jacques Rousseau

ABSTRACTWe designed novel pre-drug compounds that transform into an active form that covalently modifies particular His residue in the active site, a difficult task to achieve, and applied to carbonic anhydrase (CAIX), a transmembrane protein, highly overexpressed in hypoxic solid tumors, important for cancer cell survival and proliferation because it acidifies tumor microenvironment helping invasion and metastases processes. The designed compounds have several functionalities: 1) primary sulfonamide group recognizing carbonic anhydrases (CA), 2) high-affinity moieties specifically recognizing CAIX among all CA isozymes, and 3) forming a covalent bond with the His64 residue. Such targeted covalent compounds possess both high initial affinity and selectivity for the disease target protein followed by complete irreversible inactivation of the protein via covalent modification. Our designed prodrug candidates bearing moderately active pre-vinyl sulfone esters or weakly active carbamates optimized for mild covalent modification activity to avoid toxic non-specific modifications and selectively target CAIX. The lead inhibitors reached 2 pM affinity, highest among known CAIX inhibitors. The strategy could be used for any disease drug target protein bearing a His residue in the vicinity of the active site.

Namen raziskave je preučiti vpliv digitalizacije na visoko šolstvo, predvsem v smiludigitalnihkompetenc,kijihdanespotrebujevisokošolskišudentvštudij skemprocesuinpriizvajanju študijskih obveznosti. V prvem delu smo analizi rali posledice digitalnega preboja v visokem šolstvu, v drugempaidentificirati digitalnekompetence,kijihdanespotrebujevisokošolskištudent.Pritemsmo izhajali iz Evropskega kompetenčnega okvira za razvijanje in razumevanje di gitalne kompetence DigComp, ki opredeljuje pet kompetenčnih področij: in formacije, komunikacijo, ustvarjanje vsebin, varnost in reševanje problemov. Iz analize je razvidno, da so med visokošolskimi študenti najbolj v rabi kom petence, ki se navezujejo na prvo od petih kompetenčnih področij. Analiza odraža razsežnosti akademskega digitalnega okolja in poslovanja ter odpira vprašanje,kjeinkakoštudentomzagotovitirazvojustreznihdigitalnihkompe tenczauspešnodelovanjevdigitalnemvisokošolskemokolju.Vfaziintenzivne digitalizacije poslovnih modelov, tudi v visokem šolstvu, so namreč ustrezno razvite digitalne kompetence izhodišče za uspešno delovanje.

Povzetek V članku je predstavljen model transformacije pehotnega oddelka, voda in čete. Članek se začne z ugotovitvijo, da se je karakter vojne v 21. stoletju spremenil, in ugotavlja tudi, v katerih elementih. Pri tem izhaja iz predpostavke, da so trenutni pehotni oddelek, vod in četa v večini vojsk Nata utemeljeni na karakterju bojevanja iz obdobja obeh svetovnih vojn. Ker se je spremenil bojevanja, bi bilo logično, da so se spremenili tudi pehotni oddelek, vod in četa v smislu doktrine, organizacije, kulture, usposabljanja, tehnologije itn. Toda, kot ugotavljam v članku na podlagi študije primera kopenske vojske ZDA, večinoma ni tako. Zato je v članku na podlagi transformacijske teorije predstavljen model razmišljanja o nujnih spremembah. Ključne besede Pehotni oddelek, pehotni vod, pehotna četa, karakter vojne, transformacijska teorija. Abstract This article offers a model for transforming the infantry squad, platoon and company. It begins by establishing the elements of the changed character of war in the 21st century, the assumption being that the basis for the current infantry squad, platoon and company, in NATO armies, lies in the character of war as it was during the two World Wars. Since the character of war has changed, it should be logical that this is also the case with infantry squad, platoon and company in terms of their doctrine, organization, culture, training, technology, and so on. However, as the article shows, using a US case study, this is not quite the case, so the article uses transformation theory to offer a model of thinking about the necessary changes. Key words Infantry squad, infantry platoon, infantry company, character of war, transformation theory,

Este trabalho buscou entender os conceitos de vontade de todos, vontade do corpo e vontade geral em Rousseau, buscando a relação destes com a ideia de tirania do povo e a participação do povo no poder. Vimos que quem ocupa a centralidade da filosofia política de Rousseau é o seu conceito de vontade geral, regendo o Estado legítimo e retirando a virtude da centralidade do núcleo argumentativo da filosofia política e que a vontade geral lida com a ideia de tirania do povo através de um mecanismo que exclui a vontade de todos e coloca o povo como corpo soberano e legislador, o que define uma boa forma de governo.

Los esfuerzos realizados por los diferentes gobiernos en alianza con organizaciones juveniles, empresariales y la OIT han dado, después de muchos años, frutos positivos. Según datos recientes publicados en el informe Tendencia Mundiales del Mercado Juvenil 2015 de la OIT -publicado hace unos meses- existe una tendencia a la disminución del desempleo juvenil y al aumento de la escolaridad en varios países del mundo, lo que representa una gran esperanza para la juventud; sin embargo, como lo expresa el mismo informe esta tendencia no se ha presentado de manera homogénea en todos los países y/o regiones del planeta, por lo que los esfuerzos deben seguir realizándose. En el caso de Nicaragua, las estadísticas de desempleo juvenil siguen estancadas por lo que el llamado a la acción aún está vigente a pesar de las distintas iniciativas, planes, políticas y programas impulsados por los distintos actores sociales y gubernamentales de cara a contrarrestar la crisis del desempleo juvenil. El objetivo del presente trabajo denominado “Nicaragua: ¿hacia una ley del primer empleo juvenil?”, es rescatar una de las iniciativas impulsadas desde la Asamblea Nacional y dar continuidad al debate teórico sobre la importancia de una Ley de primer empleo juvenil en nuestro país.

Nicolas Volcyr fu dottore in teologia, maître ès arts e lettore all’Università. Successivamente divenne segretario del duca Antoine de Lorraine, di cui fu lo storico ufficiale. Tra le sue opere più importanti vengono ricordate un trattato sulla musica gregoriana del 1501, un’epopea sulla gloria del duca di Lorraine del 1526 (L’histoire et recueil de la triomphante et glorieuse victoire obtenue contre les séduits et abusés luthériens), alcuni trattati di polemica religiosa e di storia. Fu trad...

Résumé Dans son article «Vampires» du Dictionnaire philosophique , Voltaire évoque le phénomène de la «peste vampirique» qui a frappé l’Europe centrale des années 30 du XVIII e siècle, aussi bien que les interprétations controversées qui en furent alors données, en France comme dans toute l’Europe. Il profite de cette occasion pour reprendre sa polémique anti-religieuse avec une ironie corrosive qui n’épargne pas même un voltairien sincère, comme Jean-Baptiste Boyer d’Argens, qui avait, avec beaucoup d’acuité, donné lui-même une interprétation du phénomène dans ses Lettres juives . Dans son texte, Voltaire choisit l’arme de la satire plutôt que celle de l’enquête scientifique. Il nous donne ainsi une approche anthropologique assez approximative en révélant par là les limites d’une raison polémique bornée à la simple idéologie.

Influence of Heart Rate and Inhibition of Autonomic Tone on the QT Interval" by Ahnve and Vallin.I Their study confirms observations previously made in man in our laboratory.'Ahnve and Vallin also questioned in their discussion that "both heart rate and adrenergic activity affect the duration of the QT interval, but it is not clear as to what extent these effects are interrelated or whether the heart rate effects are independent of autonomic tone.We demonstrated in intact unanesthesized man and in one patient after cardiac transplantation that intravenous infusion of isoproterenol did not modify the dura- tion of the QT interval independent of its effects on heart rate.3In the patient with the cardiac transplant, the QT interval was markedly short- ened at any given heart rate; however, we did not know whether that could be a normal finding in the denervated human heart.

A field sampling program was conducted on Cattaraugus and Buttermilk Creeks, New York during November and December 1977 to investigate the transport of radionuclides in surface waters as part of a continuing program to provide data for application and verification of Pacific Northwest Laboratory's (PNL) sediment and radionuclide transport model, SERATRA. Suspended sediment, bed sediment, and water samples were collected during mean flow conditions over a 45 mile reach of stream channel. Radiological analysis of these samples included primarily gamma ray emitters; however, some plutonium, strontium, curium, and tritium analyses were also included. The principal gamma emitter found during the sampling program was /sup 137/Cs where, in some cases, levels associated with the sand and clay size fractions of bed sediment exceeded 100 pCi/g. Elevated levels of /sup 137/Cs and /sup 90/Sr were found downstream of the Nuclear Fuel Services Center, an inactive plutonium reprocessing plant and low level nuclear waste disposal site. Based on radionuclide levels in upstream control stations, /sup 137/Cs was the only radionuclide whose levels in the creeks downstream of the site could confidently be attributed to the site during this sampling program. This field sampling effort is the first of a three phase program to collect data during low, medium and high flow conditions.