Ension

Plusieurs projets de développement, avec l’ambition explicite d’associer mise en patrimoine et développement local, ont été créés récemment au Maroc, dans le sillage des activités génératrices de revenus ou du pro-poor tourism. À partir de l’analyse d’une initiative de logement chez l’habitant dans la médina de Fès, nous adoptons une approche territoriale du patrimoine et du tourisme. En considérant le territoire de la médina de Fès comme une ressource touristique et patrimoniale, nous montrons que sa valeur est variable en fonction de chaque acteur. La production patrimoniale de la médina apparaît tributaire des tensions entre ceux qui veulent profiter de l’activité touristique pour préserver le patrimoine de la médina et ceux qui s’appuient sur sa valeur patrimoniale pour développer une activité touristique.

Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, β-hydroxy-β-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5 mM), alanine (0.5 mM), valine (0.5 mM), EX527 (SIRT1 inhibitor, 25 μM), and Compound C (AMPK inhibitor, 25 μM) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

Purpose: Computational fluid dynamics (CFD) is increasingly common in optimization of blood pump designs. Ension is leveraging CFD techniques for analysis of a novel pump-oxygenator which utilizes a hollow fiber membrane (HFM) rotor. This application is unusually demanding due to the geometric complexity of the HFM rotor over traditional pump vanes. The purpose is to identify a porous media analog of the HFM rotor to reduce the computational demands of CFD analysis. Methods: A miniature HFM rotor was developed to minimize the fluid domain and allow direct modeling of each fiber geometry in the rotor. A computational mesh was created in Gambit (∼12 million cells) and simulated in Fluent v6 (Fluent, Inc. Lebanon, NH). After completion of the direct model analysis, a periodic interstitial fluid domain of the HFM rotor was modeled and simulated at flow velocities observed in the direct model simulations allowing derivation of porous media characteristics of the HFM rotor. A new computational model of the miniaturized rotor was developed, replacing the individual fiber geometries with a porous media region. Results: Both the direct fiber and porous media models were verified with experimental data and showed good agreement. The porous media approach allowed for a reduction of the computational mesh from 12 million to 2 million cells, with very little loss in accuracy. This strategy is being used by Ension to model and optimize full-scale pump-oxygenator configurations.

Current mass exchange technology is not suitable for chronic applications - particularly in adult patients. One clinically important example is the absence of an extended pulmonary support system for use in bridge-to-transplant applications. Such a system presents unique and challenging functionality and biocompatibility requirements. A development effort is ongoing at the Universities of Pittsburgh and Maryland to develop a novel, active-mixing, pump-oxygenator as an adult bridge-to-transplant system. The rotating porous impeller simultaneously affects gas exchange and blood pumping. Our goal is a pump-oxygenator containing less than 0.5 m/sup 2/ of total fiber surface area capable of sustaining basal gas exchange rates of 250 ml O/sub 2//min and 200 ml CO/sub 2//min at a blood flow rate of 5 lpm and a device life of 21 days. Prototype devices have demonstrated exceptionally efficient oxygen and carbon dioxide exchange and acceptable blood pumping and biocompatibility characteristics both in vitro and ex vivo in studies up to 5 days in duration.