Contrôle tridimensionnel de bactéries magnétotactiques agissant comme microrobots pour le transport actif de médicament vers une tumeur

RÉSUMÉ En 2012, le cancer se classait comme première cause de mortalité au Canada. Parmi les traitements disponibles pour contrer cette maladie, la chimiothérapie demeure un des traitements les plus utilisés. Malgré les progrès au niveau du développement de nouveaux agents thérapeutiques utilisés en chimiothérapie, leur manque de spécificité envers les cellules cancéreuses entraîne d’importants effets secondaires chez les patients. En effet, le fonctionnement de cette thérapie, administrée de façon systémique, repose sur la diffusion passive du médicament à travers l’organisme du patient dans l’espoir qu’une portion de la dose administrée entre en contact et affecte les cellules cancéreuses. Malheureusement, en utilisant un tel système de livraison d’agents thérapeutiques, la dose thérapeutique administrée au patient dépasse largement celle que le site tumoral nécessite et l’excédent affecte négativement les régions saines. Le laboratoire de NanoRobotique de l’École Polytechnique de Montréal mise actuellement sur une nouvelle plateforme de livraison de médicaments qui permettra de complémenter les traitements de chimiothérapie. Cette plateforme cherche à exploiter les progrès technologiques en microrobotique afin de d’utiliser un microrobot autopropulsé et dirigeable à distance pouvant être guidé activement vers un site tumoral. La charge thérapeutique requise serait établie, ajoutée au biotransporteur et dirigée directement dans la tumeur. Ce faisant, les effets secondaires indésirables que les traitements de chimiothérapie causent actuellement aux régions saines du corps seraient réduits au grand bénéfice du patient. Le microbiotransporteur retenu consiste en des bactéries magnétotactiques MC-1 ne mesurant que 2 μm de diamètre. Celles-ci peuvent être contrôlées à distance par l’intermédiaire de champs magnétiques. En effet, ces bactéries ont la capacité de s’orienter en fonction du champ magnétique grâce à la présence d’une chaîne de nanoparticules magnétiques contenues dans leur cellule. L’objectif de ce projet de recherche était de développer une plateforme de contrôle beaucoup plus avancée pour regrouper les bactéries magnétotactiques en agrégats et de les diriger à distance et de façon tridimensionnelle à l’aide de techniques informatiques nouvellement crées et de valider nos résultats par des essais sur des animaux, anticipant la possibilité d’éventuellement l’appliquer à l’être humain.----------ABSTRACT In 2012, cancer was ranked as the leading cause of death in Canada. Among the treatments available for this disease, chemotherapy remains one of the most used treatments. Despite progress in the development of new therapeutic agents used in chemotherapy, their lack of specificity to reach cancer cells results in significant side effects in patients. Indeed, the application of this systemically administered therapy is based on the passive diffusion of the drug throughout the patient's body in the hope that a sufficient quantity will reach the cancer cells. Unfortunately, this method of delivering therapeutic agents requires doses that far exceed the dose required for the tumor and the excess negatively affects healthy regions. The NanoRobotics laboratory of École Polytechnique de Montreal is currently developing a new drug delivery platform that could complement chemotherapy treatment. The platform seeks to exploit technological advances in microrobotics to make use of a self-propelled microrobot that can be remotely guided to a tumor site. The proper amount of medication would be determined, loaded onto the microrobot and channeled directly to the tumor. In doing so, the adverse side-effects that chemotherapy treatment to non-selected areas of the body now causes would be reduced to benefit of the patient’s well-being. The microbiotransporter is made up of MC-1 magnetotactic bacteria measuring only 2 μm in diameter. They can be remotely controlled via magnetic fields. Indeed, these bacteria have the ability to be guided by the magnetic field due to the presence of a chain of magnetic nanoparticles contained in the cell. The objective of this research project was to develop a more advanced control platform to aggregate magnetotactic bacteria and remotely direct them in a three-dimensional manner using newly created computer software and to validate our results by experiments on animals, anticipating the opportunity of applying this technology on humans. An analysis was first conducted on the behavior of magnetotactic bacteria when exposed to high intensity magnetic fields in order to assess their control limitations. A description of the newly designed experimental platform is presented. Also described is the simulation software that was conceived to predict the behavior of these organisms when exposed to the platform’s magnetic fields

Combustion of a coal char particle in a stream of dry gas.

The burning rate, surface temperature, drag, and extinction conditions of a single char particle moving in a gas are computed numerically. The effects of the size and velocity of the particle and of the temperature and composition of the gas are examined in the framework of a simple model that includes O2 and CO2 heterogeneous reactions and, in some cases, a diffusion-controlled CO oxidation flame in the gas around the particle. In agreement with known results, the burning rate is found to increase with the velocity of the particle when the Reynolds number of the gas flow ceases to be small. The temperature of the particle increases with the temperature and oxygen mass fraction of the gas and is little affected by the size and velocity of the particle, except in the vicinity of extinction. The drag coefficient is a decreasing function of the particle size and velocity in the range of Reynolds numbers that has been analyzed. The presence of CO2 in the gas may have an important effect on the gasification of small particles

Del empirismo hacia la razón

Palau, X, 183724 o considera impreso en 191

Del empirismo hacia la razón

Palau lo considera impreso en 191

Consommateur responsable : le défaut de séduction

International audienceFace aux enjeux environnementaux de ce début du 21ème siècle, le consommateur réponsable, présenté comme le consommateur « idéal » a fait l'objet de nombreuses recherches identifiant son profil, ses pratiques et motivations. Pourtant, dans les faits, on constate de nombreuses contradictions entre les attitudes favorables énoncées et les comportements réels de consommation « réponsable ». Mobilisant une approche interprétative de type métaphorique, cet article vise à comprendre ces contradictions à partir d'une analyse compréhensive des discours de 35 consommateurs. Quatre métaphores principales (le combat, la prison, le fardeau et le troupeau) éclairent les images négatives latentes liées à la consommation réponsable, et sont ensuite discutées

SMAD4 with R361 Hotspot Mutations Retains the Ability to Bind to LEF1 and Boosts WNT Signaling in Colorectal Cancer Cells

Colorectal cancer (CRC) is one of the leading causes of deaths in the United States. Roughly 150,000 new cases are diagnosed each year, resulting in ~50,000 deaths. About 10-30% of CRC patients harbor either loss of or missense mutations in SMAD4, a critical component of the TGF-β signaling pathway. Our lab and others have shown that complete loss of Smad4 results in the increase in tumor size, microvascular density, and frequency of metastasis in CRC xenograft models. While the role of Smad4 loss in CRC progression has been extensively studied, the pathophysiological function of missense mutations in Smad4 is not fully understood. At the molecular level, these mutations usually map to the MH2 domain and eliminate residues that are involved in the formation of the heteromeric complex with regulatory Smads (R-Smads) such as Smad2/3 and ensuing transcriptional activation. These detrimental effects suggest that SMAD4 missense mutations can be categorized as loss-of-function (LOF). However, uncharacteristically for LOF mutations, they cluster in a few hotspots (e.g., R361), which is more consistent with a gain-of- or neomorphic function. Here, we investigated the functional role of Smad4 R361 mutants in vitro by re-expressing two R361 Smad4 variants in Smad4-null CRC cells. As predicted, R361 mutations disrupted Smad2/3-Smad4 heteromeric complex formation and abolished canonical TGF-β downstream signaling. In that, they were similar to SMAD4 loss. However, RNA sequencing and subsequent RT-PCR revealed that Smad4mut cells possess the known gene signature associated with enhanced LEF1 protein function and increased WNT signaling. Mechanistically, Smad4 mutant proteins retained binding to LEF1 protein and directed a commensurate increase in downstream Wnt signaling as measured by TOP/FOP luciferase assay. Consistent with these findings, human CRCs with SMAD4 missense mutations were less likely to acquire activating mutations in the key Wnt pathway gene CTNNB1 (encoding beta catenin) than CRCs with truncating SMAD4 nonsense mutations. The former was also associated with shorter survival. Collectively, these studies implicate a TGF-β ligand-independent gain of function role for mutant Smad4 in CRC

Transient Electrohydrodynamics of Low–Conductivity Drops

Chemical Engineerin

Mieux comprendre l’image du consommateur responsable : de la personne idéale aux stéréotypes négatifs

International audienc