Trade, innovation and optimal patent protection

This paper provides a first comprehensive quantitative analysis of optimal patent policy in the global economy. We introduce a new framework, which combines trade and growth theory into a tractable tool for quantitative research. Our application delivers three main results. First, the potential gains from international cooperation over patent policies are large. Second, only a small share of these gains has been realized so far. And third, the WTO's TRIPS agreement has been counterproductive, slightly reducing welfare in the Global South and for the world. Overall, there is substantial scope for policy reform

Rational Design and Characterization of D-Phe-Pro-D-Arg-Derived Direct Thrombin Inhibitors

The tremendous social and economic impact of thrombotic disorders, together with the considerable risks associated to the currently available therapies, prompt for the development of more efficient and safer anticoagulants. Novel peptide-based thrombin inhibitors were identified using in silico structure-based design and further validated in vitro. The best candidate compounds contained both l- and d-amino acids, with the general sequence d-Phe(P3)-Pro(P2)-d-Arg(P1)-P1′-CONH2. The P1′ position was scanned with l- and d-isomers of natural or unnatural amino acids, covering the major chemical classes. The most potent non-covalent and proteolysis-resistant inhibitors contain small hydrophobic or polar amino acids (Gly, Ala, Ser, Cys, Thr) at the P1′ position. The lead tetrapeptide, d-Phe-Pro-d-Arg-d-Thr-CONH2, competitively inhibits α-thrombin's cleavage of the S2238 chromogenic substrate with a Ki of 0.92 µM. In order to understand the molecular details of their inhibitory action, the three-dimensional structure of three peptides (with P1′ l-isoleucine (fPrI), l-cysteine (fPrC) or d-threonine (fPrt)) in complex with human α-thrombin were determined by X-ray crystallography. All the inhibitors bind in a substrate-like orientation to the active site of the enzyme. The contacts established between the d-Arg residue in position P1 and thrombin are similar to those observed for the l-isomer in other substrates and inhibitors. However, fPrC and fPrt disrupt the active site His57-Ser195 hydrogen bond, while the combination of a P1 d-Arg and a bulkier P1′ residue in fPrI induce an unfavorable geometry for the nucleophilic attack of the scissile bond by the catalytic serine. The experimental models explain the observed relative potency of the inhibitors, as well as their stability to proteolysis. Moreover, the newly identified direct thrombin inhibitors provide a novel pharmacophore platform for developing antithrombotic agents by exploring the conformational constrains imposed by the d-stereochemistry of the residues at positions P1 and P1′

Bradynectes ensifer n. sp. (Platyhelminthes: Macrostomorpha) from North Carolina, USA

Bradynectes ensifer is a new species of Macrostomorpha from shallow subtidal sediment in Bogue Inlet, NC, USA. It differs primarily from all other named members of the genus in the radically different shape of its copulatory stylet. We also consider historical records of currently unnamed specimens with similar stylet morphology collected from the NC coast by the late Dr. Reinhard M. Rieger and his students

Cinéma élargi

Le dossier du numéro 21-22 de la revue Décadrages constitue le second volume en langue française consacré au phénomène du cinéma élargi, pratique intermédiatique par excellence. Mais à la différence d’Extended cinéma : le cinéma gagne du terrain (édité par Philippe Dubois, Frédéric Monvoisin et Elena Biserna, Campanotto Editore, 2010), actes d’un colloque portant sur un ensemble de pratiques qui ne recoupent que périodiquement le cinéma élargi tel qu’entendu historiquement, le dossier de Décadrages s’attache à circonscrire les principaux dispositifs à travers lesquels se déploie ces manifestations, depuis les années 1960 jusqu’à la période contemporaine. Soulignant l’hétérogénéité du cinéma élargi, qui met en crise l’idéologie moderniste de la spécificité des supports d’expression, les études réunies dans ce numéro se concentrent sur des études de cas, mettant en évidence l’hybridation du cinéma avec la scène musicale underground (les performances de l’Exploding Plastic Inevitable de Warhol, la manifestation itinérante « Underground Explosion »), le happening ou les events (autour de Fluxus), l’art contemporain (à travers les œuvres de Barba, Borinski et Maljkovic), la conférence illustrée (par le biais de Frampton) ou encore la photographie (ou plutôt l’absence d’une prise en compte de la « paraphotographie » dans les études photographiques). D’autres essais, investiguant des corpus plus larges, examinent la situation au Japon ou en Allemagne. Par ailleurs, Ken Jacobs et Malcolm Le Grice, qui nous ont accordé un entretien, reviennent sur leur propre pratique, tandis que trois artistes (Borinski, Copeland & Decrauzat, Winterling) proposent des interventions sur le plan visuel