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Critical care has undergone several developments in the recent years leading to improved survival. However, acquired muscle weakness in the intensive care unit (ICU) is an important complication that affects severely ill patients and can prolong their ICU stay. Critical illness myopathy (CIM) is the progressive decline in the function and mass of the limb muscles in response to exposure to the ICU condition, while ventilator-induced diaphragm dysfunction (VIDD) is the time dependent decrease in the diaphragm function after the initiation of mechanical ventilation. Since the complete underlying mechanisms for CIM and VIDD are not completely understood, there is a compelling need for research on the mechanisms of CIM and VIDD to develop intervention strategies targeting these mechanisms. The aim of this thesis was to investigate the effects of several intervention strategies and rehabilitation programs on muscle wasting associated with ICU condition. Moreover, muscle specific differences in response to exposure to the ICU condition and different interventions was investigated. Hence, a rodent ICU model was used to address the mechanistic and therapeutic aspects of CIM and VIDD. The effects of heat shock protein 72 co-inducer (HSP72), BGP-15, on diaphragm and soleus for rats exposed to different durations of ICU condition was investigated. We showed that 5 and 10 days treatment with BGP-15 improved diaphragm fiber and myosin function, protected myosin from posttranslational modification, induced HSP72 and improved mitochondrial function. Moreover, BGP-15 treatment for 5 days improved soleus muscle fibers function, improved mitochondrial structure and reduced the levels of some ubiquitin ligases. In addition to BGP-15 treatment, passive mechanical loading of the limb muscles was investigated during exposure to the ICU condition. We showed that mitochondrial dynamics and mitophagy gene expression was affected by Mechanical silencing while mechanical loading counteracted these effects. Our investigation for other pathways that can be involved in muscle wasting associated with ICU condition showed that the Janus kinase 2/ Signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is differentially activated in plantaris, intercostals and diaphragm. However, further studies are required with JAK2/STAT3 inhibitors to fully examine the role of this pathway in the pathogenesis of CIM and VIDD prior to translation to clinical research.

La valorisation des réservoirs gaziers compacts, dits Tight Gas Reservoirs (TGR), dont les découvertes sont importantes, permettrait d’augmenter significativement les ressources mondiales d’hydrocarbures. Dans l’objectif d’améliorer la production de ces types de réservoirs, nous avons mené une étude ayant pour but de parvenir à une meilleure compréhension de la relation entre l’endommagement et les propriétés de transport des géomatériaux. L’évolution de la microstructure d’éprouvettes qui ont été soumises préalablement à des chargements dynamiques est étudiée. Une estimation de leurs perméabilités avec l’endommagement est tout d’abord présentée à l’aide d’un modèle de pores parallèles couplant un écoulement de Poiseuille avec la diffusion de Knudsen. Nous avons ensuite mené des travaux expérimentaux afin d’estimer l’évolution de la perméabilité avec l’endommagement en relation avec l’évolution de la distribution de tailles de pores. Les mesures de perméabilité sont effectuées sur des cylindres en mortier similaire aux roches tight gas, soumis à une compression uniaxiale. La caractérisation des microstructures des mortiers endommagés est réalisée par porosimétrie par intrusion de mercure. Afin d’estimer l’évolution de la perméabilité, un nouveau modèle hiérarchique aléatoire est présenté. Les comparaisons avec les données expérimentales montrent la capacité de ce modèle à estimer non seulement les perméabilités apparentes et intrinsèques mais aussi leurs évolutions sous l’effet d’un chargement introduisant une évolution de la distribution de taille de pores. Ce modèle, ainsi que le dispositif expérimental employé, ont été étendus afin d’estimer à l’avenir les perméabilités relatives de mélanges gazeux. Le dernier chapitre présente une étude de l’adsorption de méthane dans différents milieux fracturés par chocs électriques. Les résultats, utiles pour l’estimation des ressources en place, ont montré que la fracturation permet de favoriser l’extraction du gaz initialement adsorbé. / The valorization of compact gas reservoirs, called tight gas reservoirs (TGR), whose discoveries are important, would significantly increase the global hydrocarbon resources. With the aim of improving the production of these types of gas, we have conducted a study to achieve a better understanding of the relationship between damage and the transport properties of geomaterials. The microstructure evolution of specimens, which were submitted beforehand to dynamic loading, has been investigated. An estimation of their permeability upon damage is first presented with the help of a bundle model of parallel capillaries coupling Poiseuille flow with Knudsen diffusion. Then, we have carried out an experimental work to estimate the permeability evolution upon damage in relation to the evolution of the pore size distribution in uniaxial compression. The measurements of permeability have been performed on mortar cylinders, designed to mimic typical tight rocks that can be found in tight gas reservoirs. Microstructural characterization of damaged mortars has been performed with the help of mercury intrusion porosimetry (MIP). To estimate the permeability evolution, a new random hierarchical model has been devised. The comparisons with the experimental data show the ability of this model to estimate not only the apparent and intrinsic permeabilities but also their evolutions under loading due to a change in the pore size distribution. This model and the experimental set up have been extended to estimate the relative permeabilities of gas mixtures in the future. The final chapter presents a study of the adsorption of methane on different porous media fractured by electrical shocks. The results, concerning the estimation of the in-place resources, have shown that fracturing can enhance the extraction of the initial amount of adsorbed gas.

<p dir="ltr">In structural metallic components, a material’s lifecycle begins with the processing route, to produce a desired structure, which dictates the in-service performance. The variability of microstructural features as a consequence of the processing route has a direct influence on the properties and performance of a material. In order to correlate the influence processing conditions have on material performance, large test matrices are required which tend to be time consuming and expensive. An alternative route to avoid such large test matrices is to incorporate physics-based process modeling and lifing paradigms to better understand the performance of structural materials. By linking microstructural information to the material’s lifecycle, the processing path can be modified without the need to repeat large-scale testing requirements. Additionally, when a materials system is accurately modeled throughout its lifecycle, the performance predictions can be leveraged to improve the design of materials and components.</p><p dir="ltr">Ni-based superalloys are a material class widely used in many critical aerospace components exposed to coupling thermal and mechanical loads due to their increased resistance to creep, corrosion, oxidation, and strength characteristics at elevated temperatures. Many Ni-based superalloys undergo high-temperature forging to produce a desired microstructure, targeting specific strength and fatigue properties in order to perform under thermo-mechanical loads. When in-service, these alloys tend to fail as a consequence of thermo-mechanical fatigue (TMF) from either inclusion- or matrix- driven failure. In order to produce safer, cheaper and more efficient critical aerospace components, the micromechanical deformation and damage mechanisms throughout a Ni-based superalloy’s lifecycle must be understood. This research utilizes process modeling as a tool to understand the damage and deformation of inclusions in a Ni-200 matrix throughout radial forging as a means to optimize the processing conditions for improved fatigue performance. In addition, microstructural sensitive performance modeling for a Ni-based superalloy is leveraged to understand the influence TMF has on damage mechanisms.</p><p dir="ltr">The radial forging processing route requires both high temperatures and large plastic deformation. During this process, non-metallic inclusions (NMIs) can debond from the metallic matrix and break apart, resulting in a linear array of smaller inclusions, known as stringers. The evolution of NMIs into stringers can result in matrix load shedding, localized plasticity, and stress concentrations near the matrix-NMI interface. Due to these factors, stringers can be detrimental to the fatigue life of the final forged component. By performing a finite element model of the forging process with cohesive zones to simulate material debonding, this research contributes to the understanding of processing induced deformation and damage sequences on the onset of stringer formation for Alumina NMIs in a Ni-200 matrix. Through a parametric study, the interactions of forging temperature, strain rate, strain per pass, and interfacial decohesion on the NMI damage evolution metrics are studied, specifically NMI particle separation, rotation, and cavity formation. The parametric study provides a linkage between the various processing conditions parameters influence on detrimental NMI morphology related to material performance.</p><p dir="ltr">The microstructural characteristics of Ni-based superalloys, as a consequence of a particular processing route, creates a variability in TMF performance. The micromechanical failure mechanisms associated with TMF are dependent on various loading parameters, such as temperature, strain range, and strain-temperature phasing. Insights on the complexities of micromechanical TMF damage are studied via a temperature-dependent, dislocation density-based crystal plasticity finite element (CPFE) model with uncertainty quantification. The capabilities of the model’s temperature dependency are examined via direct instantiation and comparison to a high-energy X-ray diffraction microscopy (HEDM) experiment under coupled thermal and mechanical loads. Unique loading states throughout the experiment are investigated with both CPFE predictions and HEDM results to study early indicators of TMF damage mechanisms at the grain scale. The mesoscale validation of the CPFE model to HEDM experimental data provides capabilities for a well-informed TMF performance paradigm under various strain-temperature phase profiles. </p><p dir="ltr">A material’s TMF performance is highly dependent on the temperature-load phase profile as a consequence of path-dependent thermo-mechanical plasticity. To investigate the relationship between microstructural damage and TMF phasing effects, the aforementioned CPFE model investigates in-phase (IP) TMF, out-of-phase (OP) TMF, and iso-thermal (ISO) loading profiles. A microstructural sensitive performance modeling framework with capabilities to isolate phasing (IP, OP, and ISO) effects is presented to locate fatigue damage in a set of statistically equivalent microstructures (SEMs). Location specific plasticity, and grain interactions are studied under the various phasing profiles providing a connection between microstructural material damage and TMF performance.</p>