Étude de méthodes arborescentes de Monte-Carlo pour un problème de déplacement de pièces dans un atelier d'assemblage

National audienceLa recherche arborescente Monte-Carlo (MCTS) connaît un développement important pour la résolution de problèmes d'optimisation combinatoire, en particulier, lorsque les mécanismes d'inférence ne passent pas à l'échelle, ou sont trop faibles pour réduire l'espace de recherche. Dans cet article, nous appliquons la méthode MCTS à un problème de voyageur de commerce avec fenêtres de temps et contraintes de capacité, issu d'une chaîne de montage dans la construction automobile. Des adaptations du MCTS de base sont proposées et analysées via une étude expérimentale afin de dégager des pistes génériques pour la résolution de problème d'optimisation combinatoire

Role of P Glycoprotein in the Course and Treatment of Encephalitozoon Microsporidiosis

Encephalitozoon microsporidia are obligate intracellular protozoan parasites that proliferate and differentiate within a parasitophorous vacuole inside host cells that are usually epithelial in nature. Isolates of the three species of the Encephalitozoon microsporidia, E. cuniculi, E. hellem, and E. intestinalis, were obtained from AIDS patients and cultured in green monkey (E6) kidney cells. Anti-P-glycoprotein (anti-Pgp) and anti-multidrug resistance-associated protein (anti-MRP) monoclonal antibodies were used to probe for multidrug resistance (MDR) pump epitopes and verapamil- or cyclosporin A- and probenecid-modulated intracellular calcein fluorescence were used to assess the expression of Pgp and MRP respectively in uninfected and infected cells. Pgp, but not MRP, was detected immunocytochemically and by verapamil- and cyclosporin A-potentiated intracellular fluorescence in both host cells and parasite developing stages. When an in vitro infection assay was employed, verapamil and cyclosporin A acted as chemosensitizing agents for the antiparasitic drug albendazole. These observations suggest that inhibiting host cell and perhaps parasite MDR pumps may increase the efficacy of antiparasitic agents in these and other microsporidia species

Antibacterial effects of poly(2-(dimethylamino ethyl)methacrylate) against selected gram-positive and gram-negative bacteria

Antimicrobial coatings can reduce the occurrence of medical device-related bacterial infections Poly(2-(dimethylamino (dimethylamino ethyl)methacrylate) (pDMAEMA) is One Such polymer that is being researched ill this regard The aims of this study Were to (1) elucidate pDMAEMA's antimicrobial activity against a range of Gram-positive and Gram-negative bacteria and (2) to investigate its antimicrobial mode of action. The methods used include determination of minimum inhibitory concentration (MIC) values against Various bacteria and the effect of pH and temperature oil antimicrobial activity The ability of pDMAEMA to permeabilise bacterial membranes was determined using the dyes 1-N-phenyl-naphthylamine and calcein-AM, Flow cytometry was used to investigate pDMAEMA's capacity to be internalized by bacteria and to determine effects oil bacterial cell cycling. pDMAEMA was bacteriostatic against Gram-negative bacteria with MIC values between 0.1-1 mg/mL. MIC values against Gram-positive bacteria were variable pDMAEMA was active against Gram-positive bacteria around its pK(a) and at lower pH values, while it was active against Gram-negative bacteria around its pK(a) and at higher pH values. pDMAEMA inhibited bacterial growth by binding to the outside of the bacteria, permeabilizing the outer membrane and disrupting the cytoplasmic membrane By incorporating pDMAEMA with erythromycin, it was found that the efficacy of the latter was increased against Gram-negative bacteria. Together, the results Illustrate that pDMAEMA acts in a similar fashion to other cationic biocides

Optimization of the Antitumor Activity of Sequence-specific Pyrrolobenzodiazepine Derivatives Based on their Affinity for ABC Transporters

Pyrrolobenzodiazepine (PBD) derivatives are highly potent sequence-specific DNA cross-linking agents. The present study aimed to identify key physicochemical properties influencing the interaction of a series of PBDs (four dimers and 12 monomers) with the three major human ATP-binding cassette (ABC) transporters (P-gp, ABCG2, and MRP1). Isogenic cell lines expressing P-gp and ABCG2, cell lines with acquired resistance to cytotoxic agents due to the high expression of ABC transporters, and specific inhibitors against P-gp, ABCG2, and MRP1 were used. P-gp and ABCG2 decreased the permeability of the PBD dimers across cell membranes and their interaction with DNA, reducing DNA damage and the overall cytotoxic effect. PBD monomer SG-2823 formed a conjugate with glutathione and interacted with MRP1, reducing its cytotoxic effect in A549 cells. Structure–activity relationship revealed that the interaction of PBDs with the transporters could be predicted considering the molecular weight, the lipophilicity, the number of (N + O) atoms and aromatic rings, the polar surface area, the hydrogen bonding energy, and electrophilic centers. A rational design of novel PBDs with increased potency and reduced interaction with the ABC transporters is proposed