L’histoire de Cendre ou les fictions de l’arbre

Modèle ou motif, paradigme de l’unicité ou exemplification de la multiplicité, la figure de l’arbre se tient au croisement de deux images du monde. Quand la première est théorique, structurante, et, en dernier lieu, rassurante, la seconde est empirique, ouverte sur les aléas du réel, le hasard, l’accident, la dégradation. Selon que les images de l’arbre apparaissent comme des modélisations du réel, assujetties à un principe d’exactitude et d’objectivité, ou des figures poétiques n’obéissant q..

5-Nitro-3-(2-(4-phenylthiazol-2-yl)hydrazineylidene)indolin-2-one derivatives inhibit HIV-1 replication by a multitarget mechanism of action

In the effort to identify and develop new HIV-1 inhibitors endowed with innovative mechanisms, we focused our attention on the possibility to target more than one viral encoded enzymatic function with a single molecule. In this respect, we have previously identified by virtual screening a new indolinone-based scaffold for dual allosteric inhibitors targeting both reverse transcriptase-associated functions: polymerase and RNase H. Pursuing with the structural optimization of these dual inhibitors, we synthesized a series of 35 new 3-[2-(4-aryl-1,3-thiazol-2-ylidene)hydrazin-1-ylidene]1-indol-2-one and 3-[3-methyl-4-arylthiazol-2-ylidene)hydrazine-1-ylidene)indolin-2-one derivatives, which maintain their dual inhibitory activity in the low micromolar range. Interestingly, compounds 1a, 3a, 10a, and 9b are able to block HIV-1 replication with EC50 < 20 µM. Mechanism of action studies showed that such compounds could block HIV-1 integrase. In particular, compound 10a is the most promising for further multitarget compound development

Extracellular ATP acts on P2Y2 purinergic receptors to facilitate HIV-1 infection

Contact with HIV-1 envelope protein elicits release of ATP through pannexin-1 channels on target cells; by activating purinergic receptors and Pyk2 kinase in target cells, this extracellular ATP boosts HIV-1 infectivity

Thymidine- and AZT-linked 5-(1,3-dioxoalkyl)tetrazoles and 4-(1,3-dioxoalkyl)-1,2,3-triazoles

N3 of thymidine and of 3′-azido-3′-deoxythymidine (AZT) has been linked to a tetrazole ring by condensation of nucleoside-derived 2-oxonitriles with the lithium salt of 5-acetyl-1-(4-fluorobenzyl)tetrazole (obtained by a 'click' reaction). 4-Acetyl-1,2,3-triazole, also prepared by a Cu-catalysed cycloaddition, has been similarly linked. A route for the conjugation of NRTIs with pharmacophoric elements of integrase inhibitors (INIs) has thus been disclosed

Insulated gold micro singularities for high density cell trapping based on dielectrophoresis

International audienceDielectrophoresis (DEP) is broadly used in microfluidic systems for the cell therapies or medical diagnostics [1] because of its capability to handle and sort biological cells [2,3]. In this paper, a new method to trap cells on-chip with high density arraying capabilities is proposed. The principle is based on the use of metallic singularities arrayed within the flowing channel of the biochip. These singularities, even at a floating potential, induce a non uniform electrical field within the structure, responsible of a strong DEP force applied to cells. Indeed, we will demonstrate in the paper that metallic singularities generate stronger DEP forces, compared to more conventional methods where micro-dots of insulating material are arrayed to produce the electrical field traps. [4]. To the best of our knowledge, we report here the first successful use of such floating potential metallic singularities to trap cell

Etude du mode de mise en contact de phases par jets d'impact appliqué aux procédés de génération de particules en milieu supercritique

L objectif de ce travail est d étudier l influence de jets d impact libres utilisés comme mode de mise en contact des phases dans les procédés de recristallisation utilisant un fluide supercritique comme anti-solvant. L influence des variations de plusieurs paramètres opératoires sur l hydrodynamique des jets et sur les caractéristiques des poudres de Sulfathiazole a été étudiée. Les paramètres sont la vitesse des jets (de 0,25 m.s-1 à 25,92 m,s-1), le rapport molaire solvant/CO2 (de 2,5 % à 20 %), la température (de 313 K à 343 K), la pression (10 MPa à 20 MPa) et la concentration du soluté dans la solution (de 0,5 % à 1,8 %). Les conditions de mélange ont été caractérisées par l estimation des puissances dissipées par les jets d impact, variant de 0,1 à 158 W.kg-1 dans les conditions étudiées. Les résultats ont montré que la vitesse des jets et la sursaturation sont deux paramètres-clés contrôlant la cristallisation avec un effet prépondérant de la sursaturation. Les cristaux obtenus ont des tailles, distributions de taille, faciès et nature polymorphique différents selon les conditions. La forme polymorphique la plus stable a été obtenue pure ou en mélange. Une comparaison avec le procédé SAS classique a montré que les particules sont significativement plus petites lorsqu elles sont cristallisées avec les jets d impact, ce qui confirme que ce dispositif créant un mélange plus intense, permet d accélérer la cinétique de nucléation.Ce travail devrait contribuer à une meilleure maîtrise des procédés de cristallisation en milieu supercritique.The aim of this work is to study the influence of free impinging jets used for the fluids introduction in supercritical anti-solvent (SAS) processes. The influence of the variations of several operating parameters upon jets hydrodynamics and upon the powder characteristics is studied. Parameters are jets velocity (0.25 m.s-1 to 25.92 m.s-1), molar ratio solvent / CO2 (2.5 % to 20 %), temperature (313 K to 343 K), pressure (10 MPa to 20 MPa) and solute concentration in the organic solution (0.5 % to 1.8 %). Mixing conditions have been characterized estimating the dissipated powers of the impinging jets, varying from 0,1 à 158 W.kg-1 in the studied conditions. The results showed that jets velocity and supersaturation are two key-parameters controlling the crystallization with a preponderant effect of supersaturation. The obtained crystals have different size, particle size distribution, habit and polymorphic nature depending on the conditions. The most stable polymorphic form has been obtained pure or in mixture.A comparison with the classical SAS process showed that mean particle sizes are significantly smaller with impinging jets device proving that this device, creating a more efficient mixing, enhances the nucleation kinetics.This work may contribute to a better control of processes of crystallization in supercritical media.AIX-MARSEILLE3-Bib. élec. (130559903) / SudocSudocFranceF

Interplay between Intrinsic and Innate Immunity during HIV Infection

International audienc