Can A State Commit A Crime? Definitely, Yes!

As is well known, the International Law Commission (ILC) decided in 1976 to include an article in its Draft Articles on State Responsibility that makes a distinction between normal international wrongful acts, which it called delicts, on the one hand, and exceptionally grave breaches of international law which it called international crimes, on the other hand

The Charter of the United Nations: A Commentary of Bruno Simma\u27s Commentary

Review of The Charter of the United Nations: A Commentary (Bruno Simma, Hermann Mosler, Albrecht Randelzhofer, Christian Tomuschat, Rüdiger Wolfrum, Andreas Paulus, Eleni Chaitobu eds.

The Charter of the United Nations: A Commentary of Bruno Simma\u27s Commentary

Review of The Charter of the United Nations: A Commentary (Bruno Simma, Hermann Mosler, Albrecht Randelzhofer, Christian Tomuschat, Rüdiger Wolfrum, Andreas Paulus, Eleni Chaitobu eds.

SR120819A, an orally-active and selective neuropeptide Y Y1 receptor antagonist

AbstractAn orally-active antagonist of neuropeptide Y (NPY) Y1 receptors, SR 120819A, has been characterized. This compound displays highly selective and competitive affinity for rat, guinea-pig and human (Ki = 15 nM) NPY Y1 receptors. In vitro, SR 120819A blocks the inhibitory effect of NPY on adenylyl cyclase activity in human SK-N-MC cells and that of the selective Y1 agonist, [Leu31,Pro34]NPY, on rabbit vas deferens contraction (pA2 = 7.20 ± 0.07). In vivo, by intravenous route, this compound acts as an antagonist in anesthetized guinea-pigs and, notably, after oral administration, SR 120819A counteracts the pressor response of [Leu31,Pro34]NPY (5 μg/kg i.v.) with a long duration of action (>4 h at 5 mg/kg p.o.). Thus, SR 120819A is the first orally-effective NPY Y1 receptor antagonist yet descrobed. It could be a useful tool for exploring the role of NPY and the therapeutic relevance of an antagonist at NPY Y1 receptors

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

Reservations to Treaties and the Integrity of Human Rights

International audience[No abstract

Roumanie c. Ukraine - un arrêt refondateur

International audience[No abstract