Le sepsis est défini par l’apparition de dysfonctions d’organes, multiples et mortelles, causées par une réponse de l’hôte dérégulée suite à une infection. L’hétérogénéité de la maladie représente un défi clinique majeur au regard de la prise en charge thérapeutique, et à ce jour les marqueurs proposés ne suffisent pas à stratifier les patients. Les rétrovirus endogènes humains (HERV) pourraient être des marqueurs pertinents,compte tenu des propriétés immunosuppressives de leurs enveloppes et de leur expression dans des maladies inflammatoires et auto-immunes. Cette thèse a pour objectif de savoir dans quelle mesure les HERV sont exprimés et modulés, dans des conditions d’inflammation et d’immunosuppression. Pour cela,nous avons utilisé une puce à ADN haute densité permettant (i) l’analyse de la transcription de 363 689HERV et 1500 gènes, et (ii) une lecture fonctionnelle de l’activité des LTR. L’expression des HERV a été objectivée (i) dans un modèle ex-vivo de tolérance à l’endotoxine sur des cellules mononuclées du sang périphérique (PBMC) d’individus sains et (ii) sur sang total provenant d’individus sains et de patients en choc septique, stratifiés ou non en fonction du statut immunitaire. (1) De 5,6% à 6,9% des HERV sont exprimés dans le compartiment sanguin et environ 20% des LTR possèdent une fonction promotrice ou polyA, les deux fonctions étant mutuellement exclusives. (2) Le contenu du transcriptome HERV est modulé ex vivo dans le contexte de tolérance à l’endotoxine laissant apparaitre deux grands phénotypes transcriptionnels. L’expression de certains loci HERV est corrélée au statut immunitaire de patient septique.L’évaluation d’une signature moléculaire complexe sur une cohorte de validation, permet la séparation en deux groupes présentant des critères de sévérité distincts, suggérant les HERV/MaLR comme biomarqueurs de stratification. (3) L’analyse de la co-expression des gènes et des HERV a permis d’intégrer ceux-ci au sein de réseaux associées à la réponse de l’hôte et de proposer des hypothèses fonctionnelles. / Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.The heterogeneity of the disease present a major clinical challenge with regard to the therapeutic coverage,and this day the proposed markers are not enough to stratify patients. The human endogenous retrovirus(HERV) could be relevant markers, considering the immunosuppressives properties of their envelopes andtheir expression in inflammatory and autoimmune disease. The aim of this thesis is to know to what extentthe HERVs are expressed and modulated, in inflammatory and immunocompromised contexts. For this, weused a high density DNA chip allowing (i) the transcription analysis of 363,689 HERV and 1500 genes,and (ii) a functional reading of LTRs activities. The HERVs expression was objectified (i) in endotoxintolerance ex vivo model in peripheral blood mononuclear cells (PBMCs) of healthy volunteers and (ii) inwhole blood of healthy volunteers and septic shock patients, stratified or not according to immunity state.(1) Of 5,6% at 6,9% of HERVs are expressed in the blood compartment and around 20% of LTRs have apromoter or polyA function, both functions being mutually exclusive. (2) The HERV transcriptome ismodulated in ex vivo endotoxin tolerance model letting appear two higher transcriptional phenotypes. Theexpression of some HERVs loci are correlated of the immunity state of the septic shock patients. Theevaluation of molecular signature in validation cohort, allowed to separate in two patients groupspresenting different severity criteria, suggesting HERV/MaLR as biomarkers of stratification. (3) The coexpressedanalysis of genes and HERVs allowed to integrate these within signaling pathways associated atthe host immune response and to provide functional hypothesis.

Many studies of the fire induced thermal and structural behaviour in large compartments, carried out over the past two decades, show a great deal of non-uniformity, unlike the homogeneous compartment temperature assumption in the current fire safety engineering practice. Furthermore, some large compartment fires may burn locally and they tend to move across entire floor plates over a period of time as the fuel is consumed. This kind of fire scenario is beginning to be idealized as 'travelling fires' in the context of performance‐based structural and fire safety engineering. However, the previous research of travelling fires still relies on highly simplified travelling fire models (i.e. Clifton's model and Rein's model); and no equivalent numerical tools can perform such simulations, which involves analysis of realistic fire, heat transfer and thermo-mechanical response in one single software package with an automatic coupled manner. Both of these hinder the advance of the research on performance‐based structural fire engineering. The author develops an extended travelling fire method (ETFM) framework and an integrated comprehensive tool with high computational expediency in this research, to address the above‐mentioned issues. The experiments conducted for characterizing travelling fires over the past two decades are reviewed, in conjunction with the current available travelling fire models. It is found that no performed travelling fire experiment records both the structural response and the mass loss rate of the fuel (to estimate the fire heat release rate) in a single test, which further implies closer collaboration between the structural and the fire engineers' teams are needed, especially for the travelling fire research topic. In addition, an overview of the development of OpenSees software framework for modelling structures in fire is presented, addressing its theoretical background, fundamental assumptions, and inherent limitations. After a decade of development, OpenSees has modules including fire, heat transfer, and thermo‐mechanical analysis. Meanwhile, it is one of the few structural fire modelling software which is open source and free to the entire community, allowing interested researchers to use and contribute with no expense. An OpenSees‐based integrated tool called SIFBuilder is developed by the author and co‐workers, which can perform fire modelling, heat transfer analysis, and thermo-mechanical analysis in one single software with an automatic coupled manner. This manner would facilitate structural engineers to apply fire loading on their design structures like other mechanical loading types (e.g. seismic loading, gravity loading, etc.), without transferring the fire and heat transfer modelling results to each structural element manually and further assemble them to the entire structure. This feature would largely free the structural engineers' efforts to focus on the structural response for performance-based design under different fire scenarios, without investigating the modelling details of fire and heat transfer analysis. Moreover, the efficiency due to this automatic coupled manner would become more superior, for modelling larger structures under more realistic fire scenarios (e.g. travelling fires). This advantage has been confirmed by the studies carried out in this research, including 29 travelling fire scenarios containing total number of 696 heat transfer analysis for the structural members, which were undertaken at very modest computational costs. In addition, a set of benchmark problems for verification and validation of OpenSees/SIFBuilder are investigated, which demonstrates good agreement against analytical solutions, ABAQUS, SAFIR, and the experimental data. These benchmark problems can also be used for interested researchers to verify their own numerical or analytical models for other purposes, and can be also used as an induction guide of OpenSees/SIFBuilder. Significantly, an extended travelling fire method (ETFM) framework is put forward in this research, which can predict the fire severity considering a travelling fire concept with an upper bound. This framework considers the energy and mass conservation, rather than simply forcing other independent models to 'travel' in the compartment (i.e. modified parametric fire curves in Clifton's model, 800°C‐1200°C temperature block and the Alpert's ceiling jet in Rein's model). It is developed based on combining Hasemi's localized fire model for the fire plume, and a simple smoke layer calculation by utilising the FIRM zone model for the areas of the compartment away from the fire. Different from mainly investigating the thermal impact due to various ratios of the fire size to the compartment size (e.g. 5%, 10%, 25%, 75%, etc.), as in Rein's model, this research investigates the travelling fire thermal impact through explicit representation of the various fire spread rates and fuel load densities, which are the key input parameters in the ETFM framework. To represent the far field thermal exposures, two zone models (i.e. ASET zone model & FIRM zone model) and the ETFM framework are implemented in SIFBuilder, in order to provide the community a 'vehicle' to try, test, and further improve this ETFM framework, and also the SIFBuilder itself. It is found that for 'slow' travelling fires (i.e. low fire spread rates), the near‐field fire plume brings more dominant thermal impact compared with the impact from far‐field smoke. In contrast, for 'fast' travelling fires (i.e. high fire spread rates), the far‐field smoke brings more dominant thermal impact. Furthermore, the through depth thermal gradients due to different travelling fire scenarios were explored, especially with regards to the 'thermal gradient reversal' due to the near‐field fire plume approaching and leaving the design structural member. This 'thermal gradient reversal' would fundamentally reverse the thermally‐induced bending moment from hogging to sagging. The modelling results suggest that the peak thermal gradient due to near‐field approaching is more sensitive to the fuel load density than fire spread rate, where larger peak values are captured with lower fuel load densities. Moreover, the reverse peak thermal gradient due to near‐field leaving is also sensitive to the fuel load density rather than the fire spread rate, but this reverse peak value is inversely proportional to the fuel load densities. Finally, the key assumptions of the ETFM framework are rationalised and its limitations are emphasized. Design instructions with relevant information which can be readily used by the structural fire engineers for the ETFM framework are also included. Hence more optimised and robust structural design under such fire threat can be generated and guaranteed, where we believe these efforts will advance the performance‐based structural and fire safety engineering.

The medical use of marijuana is increasing, yet little is known about the exposure-response relationships resulting in its psychoactive effects. Δ9-tetrahydrocannabinol (THC) and its active metabolite (11-hydroxy-THC; THC-OH) are the principal psychoactive components in marijuana. It is well known that the plasma concentrations of the psychoactive components of marijuana do not directly relate to the observed psychoactive effects. The presence of a counter-clockwise hysteresis in the plasma concentrations-effect plot demonstrates a temporal delay between the plasma concentrations and observed effect following the intravenous administration of THC. The overarching objective of this research was to better understand the relationship between the plasma and brain concentrations of the psychoactive components (THC and THC-OH) and the observable psychoactive effects after intravenous administration of THC, utilizing model-based approaches. Specifically, the pharmacokinetics were explored using population pharmacokinetic (Pop PK) and physiologically-based pharmacokinetic (PBPK) modeling whereas the pharmacodynamics (PD) of the psychoactive effect (“highness”) were explored using effect-compartment modeling and linking the PD to the PBPK-derived concentrations predicted in the brain and an assumed effect-site. A “hypothetical” effect compartment model was developed to characterize the observed delay in peak “highness” ratings. A direct relationship was established between the reported psychoactive effects (“highness” or intoxication) and the predicted effect-site concentrations of both components (THC and THC-OH) using this effect-compartment modeling approach. The faster plasma to effect compartment equilibration for THC-OH indicated a more rapid equilibration of the active metabolite between plasma and the effect-site (biophase) than for the parent THC. In addition, a PBPK modeling approach was pursued to predict and relate the brain concentrations of THC and THC-OH to the psychoactive effect. The relationship between the effect and the predicted unbound brain concentration of THC indicated an indirect relationship, suggesting a temporal delay between brain concentrations of THC and observed effect. However, a direct relationship was observed between the observed effect and the unbound brain THC-OH concentrations. In addition, the unbound concentrations of THC-OH in the brain were predicted to be higher than the corresponding THC concentrations. These findings highlight the importance for the inclusion of THC-OH, in addition to THC, when relating the observed effect to the concentrations of the psychoactive components of marijuana. These models contribute to the understanding of the PK-PD relationships associated with marijuana use and are important steps in the prediction of the pharmacodynamic effects related to the psychoactive components in marijuana and establish an approach for investigating other THC-related effects.

En el presente trabajo, utilizamos técnicas de microfabricación, simulaciones numéricas, experimentos de electrofisiología para explorar la viabilidad en me- jorar la interface ordenador-neurona a través de microcanales, y la biofísica para la generación de señales en los dispositivos con microcanales. También demos- tramos que los microcanales pueden ser usados como una técnica prometedora con alto rendimiento en el muestreo automático de canales iónicos a nivel subce- lular. Finalmente, se ha diseñado, fabricado y probado el micropozo-microcanal como modificación adicional a los arreglos de multielectrodos, permitiendo una alta ganancia en la relación señal/ ruido (en inglés Signal to Noise Ratio SNR), y el registro de múltiples-lugares en poblaciones de baja densidad de redes neu- ronales del hipocampo in vitro. Primero, demostramos que son de alto rendimiento los microcanales de bajo costo con interface neurona-electrodo, para el registro extracelular de la activi- dad neuronal con baja complexidad, por periodos estables de larga duración y con alta ganancia SNR. En seguida, se realiza un estudio mediante experimentos y simulaciones nu- méricas de la biofísica para la generación de las señales obtenidas de los dispositi- vos con microcanales. Basados en los resultados, racionalizamos y demostramos como es que la longitud del canal (siendo 200 μm) y la sección transversal del microcanal (siendo 12 μm2) canaliza a los potenciales de acción para estar dentro del rango de milivolts. A pesar del bajo grado de complexidad envuelto en la fabricación y aplicación, los dispositivos con microcanales otorgan una sola media de valor SNR de 101 76, lo cual es favorablemente comparable con la SNR que se obtiene de desarrollos recientes que emplean electrodos curados con CNT y Si-NWFETs. Más aún, nosotros demostramos que el microcanal es una técnica promete- dora para el alto rendimiento del muestro automático de canales iónicos a nivel subcelular: (1) Información experimental y simulaciones numéricas sugieren que las señales registradas sólo afectan los parches membranales localizados dentro del microcanal o alrededor de 100 μm de las entradas del microcanal. (2) La transferencia de masa de los componentes químicos en los microcanales fue ana- lizada por experimentos y simulaciones FEM. Los resultados muestran que los microcanales que contienen glía y tejido neuronal pueden funcionar como barre- ra de fluido/química. Los componentes químicos pueden ser solamente aplicados a diferentes compartimentos a nivel subcelular. Finalmente, basado en simulaciones numéricas y resultados experimentales, se propone que del micropozo-microcanal, obtenido de la modificación de MEA (MWMC-MEA), la longitud óptima del canal debe ser 0,3 mm y la posición 1 óptima del electrodo intracanal, hacia la entrada más cercana del microcanal, debe ser 0,1 mm. Nosotros fabricamos un prototipo de MWMC-MEA, cuyo hoyo pasante sobre las películas de Polydimethylsiloxane (PDMS) fue microtrabajado a través de la técnica de grabados reactivos de plasma de iones. La baja densidad del cultivo (57 neuronas /mm2) en el MWMC-MEAs permitió que las neuronas vivieran al menos 14 días, con lo que la señal neuronal con la máxima SNR obtenida fue de 142. 2 / In this present work, we used microfabrication techniques, numerical simulations, electrophysiological experiments to explore the feasibility of enhancing neuron-computer interfaces with microchannels and the biophysics of the signal generation in microchannel devices. We also demonstrate the microchannel can be used as a promising technique for high-throughput automatic ion-channel screening at subcellular level. Finally, a microwell-microchannel enhanced multielectrode array allowing high signal-to-noise ratio (SNR), multi-site recording from the low-density hippocampal neural network in vitro was designed, fabricated and tested. First, we demonstrate using microchannels as a low-cost neuron-electrode interface to support low-complexity, long-term-stable, high SNR extracellular recording of neural activity, with high-throughput potential. Next, the biophysics of the signal generation of microchannel devices was studied by experiments and numerical simulations. Based on the results, we demonstrate and rationalize how channels with a length of 200 μm and channel cross section of 12 μm2 yielded spike sizes in the millivolt range. Despite the low degree of complexity involved in their fabrication and use, microchannel devices provided a single-unit mean SNR of 101 76, which compares favourably with the SNR obtained from recent developments employing CNT-coated electrodes and Si-NWFETs. Moreover, we further demonstrate that the microchannel is a promising technique for high-throughput automatic ion-channel screening at subcellular level: (1) Experimental data and numerical simulations suggest that the recorded signals are only affected by the membrane patches located inside the microchannel or within 100 μm to the microchannel entrances. (2) The mass transfer of chemical compounds in microchannels was analyzed by experiments and FEM simulations. The results show that the microchannel threaded by glial and neural tissue can function as fluid/chemical barrier. Thus chemical compounds can be applied to different subcellular compartments exclusively. Finally, a microwell-microchannel enhanced MEA (MWMC-MEA), with the optimal channel length of 0.3 mm and the optimal intrachannel electrode position of 0.1 mm to the nearest channel entrance, was proposed based on numerical simulation and experiment results. We fabricated a prototype of the MWMCMEA, whose through-hole feature of Polydimethylsiloxane film (PDMS) was micromachined by reactive-ion etching. The low-density culture (57 neurons/mm2) were survived on the MWMC-MEAs for at least 14 days, from which the neuronal signal with the maximum SNR of 142 was obtained.

Decapentaplegic (Dpp), a member of the TGF-[Beta] superfamily, acts as a morphogen to direct cell differentiation, determine cell fate and promote cell survival and proliferation in Drosophila wing development. To investigate the role of Dpp in Drosophila wing development, three aspects of the patterning role of Dpp have been analyzed. First, I investigated the cellular responses to Dpp signaling by a loss of function strategy. The consequences of lacking Dpp signal transduction on cell morphology and tissue integrity were analyzed. Second, I investigated whether Dpp signaling is down-stream of Hh signaling to maintain the normal cell segregation at the A/P boundary by clonal analysis. Third, I investigated whether cross talk among the Hh, Dpp and Wg signaling pathways exists and what its relevance for wing patterning is. To investigate the role of Dpp in Drosophila wing development, the general strategies are to look at the phenotypes of loss-of-function and gain-of-function. Mutant clones lacking Dpp signal transduction by knock down Dpp receptor Thick veins (Tkv) do not survive in wing blade due to JNK dependent apoptosis. To get larger mutant clones for analysis, JNK pathway was inhibited by knock down bsk (encodes JNK) in mutant clones lacking Dpp signaling using FLP-FRT system. Clones double mutant for tkv and bsk did not undergo apoptosis, but recovered at very low frequencies compared to sibling clones. Here, I showed that the low recovery of tkv bsk double mutant clones are due to the extrusion of mutant cells. The extrusion of tkv bsk double mutant cells correlated with changes in the actin cytoskeleton and a dramatic loss of the apical microtubule web normally present in these cells. These results suggest that Dpp signaling is required for cell morphogenesis in Drosophila wing development. We propose that Dpp acts as a survival factor in the wing disc epithelium by orchestrating proper cytoskeletal organization and maintaining normal cell-cell contact. Drosophila wing is subdivided into anterior (A) and posterior (P) compartments. This developing into adjacent compartments is crucial for the patterning of Drosophila wing. Previous study has shown that Hedgehog (Hh) signaling is required in A cells to maintain the A/P boundary and is sufficient to specify A type cell sorting. A previous study has in addition implicated the signaling molecule Decapentaplegic (Dpp) in maintaining the A/P boundary. However, this study did not address whether and in which cells, A and/or P, Dpp signal transduction was required to maintain this boundary. Here, I have analyzed the role of components of the Dpp signal transduction pathway and the relation of Dpp and Hh signaling in maintaining the A/P boundary by clonal analysis. I showed that Dpp signaling mediated by the Dpp target gene, T-box protein Optomotor-blind (Omb), is required in A cells, but not in P cells, to maintain the normal position of the A/P boundary. During patterning formation, it is essential for cells to receive precise positional information to pattern the tissue. It has been proposed for a long time that different signaling pathways such as Hedgehog (Hh), Dpp and Wingless (Wg) signaling pathways provide positional information for tissue patterning in an integrated manner. Recently, evidence of interactions between Hh and Dpp as well as Wg and Hh signaling pathways has been reported in Drosophila wing. Here, I have identified additional interactions among Hh, Dpp and Notch/Wg signaling. We propose that the selector gene engrailed, Hh and Dpp signaling interact with each other to regulate target genes expression and thus to pattern the wing along the A/P axis. Further more, I showed that Dpp signaling is also participating in the patterning along the D/V axis by interaction with the selector gene apterous and Notch/Wg signaling.

Helicopters have now become an essential part for civil and military activities, for the next few years a significant increase in the use of this mean of transportation is expected. Unlike many fixed-wing aircraft, helicopters have no need to be pressurized due to their operating at low altitudes. The Environmental Control Systems (ECS) commonly used in fixed-wing aircraft are air cycle systems, which use the engine compressor’s bleed flow to function. These systems are integrated in the aircraft from inception. The ECS in helicopters is commonly added subsequently to an already designed airframe and power plant or as an additional development for modern aircraft. Helicopter engines are not designed to bleed air while producing their rated power, due to this a high penalty in fuel consumption is paid by such refitted systems. A detailed study of the different configurations of ECS for rotorcraft could reduce this penalty by determining the required power resulting from each of the system configurations, and therefore recommend the most appropriate one to be implemented for a particular flight path and aircraft. This study presents the conducted analysis and subsequent simulation of the environmental control system in a selected representative rotorcraft: the Bell206L-4. This investigation seeks to optimize the rotorcraft’s power consumption and energy waste; by taking into consideration the cabin heat load. It consequently aims to minimize these penalties, achieving passenger comfort, an optimally moist air for equipment and a reduction in the environmental impact. For the purpose of this analysis a civil aircraft was chosen for a rotary-wing type. This helicopter was analysed with different air-conditioning packs complying with the current airworthiness requirements. These systems were optimized with the inclusion of different environmental control models, and the cabin heat load model, which provided the best air-conditioning for many conditions and mission scopes, thus reducing the high fuel consumption in engines and hence the emission of gases into the environment. Each of the models was computed in the Matlab-simulink® software. Different case studies were carried out by changing aircraft, the system’s configurations and flight parameters. Comparisons between the different systems and sub-systems were performed. The results of these simulations permitted the ECS configuration selection for optimal fuel consumption. Once validated the results obtained through this model were included in Rotorcraft Mission Energy Management Model (RMEM), a tool designed to predict the power requirements of helicopter systems. The computed ECS model shows that favourable reductions in fuel burn may be achievable if an appropriated configuration of ECS is chosen for a light rotorcraft. The results show that the VCM mixed with engine bleed air is the best configuration for the chosen missions. However, this configuration can vary according to the mission and environment.

Neuronal networks produce reliable functional output throughout the lifespan of an animal despite ceaseless molecular turnover and a constantly changing environment. The cellular and molecular mechanisms underlying the ability of these networks to maintain functional stability remain poorly understood. Central pattern generating circuits produce a stable, predictable rhythm, making them ideal candidates for studying mechanisms of activity maintenance. By identifying and characterizing the regulators of activity in small neuronal circuits, we not only obtain a clearer understanding of how neural activity is generated, but also arm ourselves with knowledge that may eventually be used to improve medical care for patients whose normal nervous system activity has been disrupted through trauma or disease. We utilize the pattern-generating pyloric circuit in the crustacean stomatogastric nervous system to investigate the general scientific question: How are specific aspects of rhythmic activity regulated in a small neuronal network? The first aim of this thesis poses this question in the context of a single neuron. We used a single-compartment model neuron database to investigate whether co-regulation of ionic conductances supports the maintenance of spike phase in rhythmically bursting “pacemaker” neurons. The second aim of the project extends the question to a network context. Through a combination of computational and electrophysiology studies, we investigated how the intrinsic membrane conductances of the pacemaker neuron influence its response to synaptic input within the framework of the Phase Resetting Curve (PRC). The third aim of the project further extends the question to a systems-level context. We examined how ambient temperatures affect the stability of the pyloric rhythm in the intact, behaving animal. The results of this work have furthered our understanding of the principles underlying the long-term stability of neuronal network function.

Les prothèses myoélectriques modernes peuvent être dotées de plusieurs degrés de liberté ce qui nécessite plusieurs signaux musculaires pour en exploiter pleinement les capacités. Pour obtenir plus de signaux, il nous a semblé prometteur d'expérimenter si les 6 compartiments du biceps brachial pouvaient être mis sous tension de façon volontaire et obtenir ainsi 6 signaux de contrôle au lieu d'un seul comme actuellement. Des expériences ont donc été réalisées avec 10 sujets normaux. Des matrices d'électrodes ont été placées en surface au-dessus du chef court et long du biceps pour recueillir les signaux électromyographiques (EMG) générés par le muscle lors de contractions effectuées alors que les sujets étaient soit assis, le coude droit fléchi ~ 100 ° ou debout avec le bras droit tendu à l'horizontale dans le plan coronal (sur le côté). Dans ces deux positions, la main était soit en supination, soit en position neutre, soit en pronation. L'amplitude des signaux captés au-dessus du chef court du muscle a été comparée à ceux obtenus à partir du chef long. Pour visualiser la forme du biceps sous les électrodes l'imagerie ultrasonore a été utilisée. En fonction de la tâche à accomplir, l'activité EMG a était plus importante soit dans un chef ou dans l'autre. Le fait de pouvoir activer préférentiellement l'un des 2 chefs du biceps, même si ce n'est pas encore de façon complètement indépendante, suggère que l'utilisation sélective des compartiments pourrait être une avenue possible pour faciliter le contrôle des prothèses myoélectriques du membre supérieur. / The latest myoelectric prostheses have several degrees of freedom and therefore require a large number of myoelectric signals to fully exploit their capabilities. Muscle compartments, which are intra-muscular subdivisions innervated by an individual muscle nerve branch, can be exploited to provide additional independent muscle control sites to operate such prostheses. This research presents a work to investigate the activation of the 6 biceps brachii compartments in healthy subjects to see if they have the ability to activate those compartments voluntarily. Therefore, electromyographic (EMG) signals were recorded from an array of seven and ten pairs of equally spaced surface electrodes positioned across the short and long head of the biceps of ten healthy subjects. The EMG signals are collected in two positions: 1) with the subject seated, right elbow flexed ~100°, and 2) with the subject standing with the right arm extended horizontally in the coronal plane (90°shoulder abduction). In both positions, the hand is either fully supinated, neutral, or fully pronated. The average root mean square value of the EMG signals obtained from the pairs of electrodes positioned over the short head are compared with the average obtained for the other pairs placed over the biceps long head. Ultrasound imaging also used to visualize the long and short heads of the biceps in flexed and extended arm while the hand was in different postures. Depending on the task to be accomplished, activity was larger in one head or in the other. Being able to activate either head of the biceps, while not yet completely independently, suggests that the selective use of compartments could be a possible avenue for controlling upper limb myoelectric prostheses.

Nhx1 est un antiport vacuolaire de Na+/H+ chez la levure Saccharomyces cerevisiae. Nhx1 joue un rôle important dans le maintien de l’homéostasie ionique du cytoplasme de la cellule. En effet, la mutation du gène NHX1 chez la levure nhx1Δ entraîne une perte de l’homéostasie cellulaire quand les cellules sont cultivées dans un milieu de faible osmolarité. Ce travail rapporte pour la première fois, et contrairement à la cellule parentale, que la mutation du gène NHX1 a pour effet une sensibilité du mutant nhx1Δ à une variété des drogues et des agents cationiques et anioniques lorsque les cellules sont cultivées dans un milieu riche. En outre, dans ces conditions de culture, aucune sensibilité n’a été observée chez le mutant nhx1Δ quand les cellules sont traitées avec différentes concentrations de sel. Nous avons aussi démontré que la sensibilité du mutant nhx1Δ aux différents agents ainsi que la sécrétion de l’enzyme carboxypeptidase Y observé chez ce mutant n’ont pas été restauré lorsque les cellules sont cultivées dans des milieux avec différents pH ou avec différentes concentrations de sel. Enfin, une analyse génétique a révélé que le mutant nhx1Δ montre un phénotype distinct d’autres mutants qui ont un défaut dans le trafic entre le compartiment pré-vacuolaire et l’appareil de Golgi quand ces cellules sont traitées avec différents agents. Cette analyse prouve que la sensibilité de nhx1Δ aux différents agents n’est pas liée au trafic entre le compartiment pré-vacuolaire et l’appareil de Golgi. / Nhx1 is an intracellular Na+/H+ exchanger localized to the late endosome in Saccharomyces cerevisiae. It is believed that Nhx1 plays a major role in pH-mediated vesicle trafficking, as nhx1Δ mutant is defective in maintaining the intracellular pH in the vacuoles and cytoplasm when grown in low osmolarity media. In this work, we reported novel drug sensitivities of the nhx1Δ mutant to a range of cationic and anionic agents when cells are grown in rich media. Unlike the low osmolarity media, the nhx1Δ mutant showed no sensitivity to salt. Furthermore, we showed that the drug phenotypes of the nhx1Δ mutant, as well as the secretion of the vacuolar protein carboxypeptidase Y, were not rescued by either altering the pH or salt concentration. Although, amino acid substitution of the phylogenetically conserved residue Glu355 for Ala (E355A) in Nhx1 resulted in sensitivity to genotoxic drug bleomycin, it was not observed for the non-conserved residue Glu371Ala (E371A). Moreover, genetic analysis revealed that the nhx1Δ mutant displayed distinct drug phenotypes in comparison to mutants that are defective in retrograde trafficking from the prevacuole to the late Golgi, excluding the possibility that the drug sensitivity of the nhx1Δ mutant is related to retrograde trafficking.

Colonic ischaemia (CI), Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are devastating complications after abdominal aortic aneurysm (AAA) surgery. The aims of this thesis were to study the incidence and clinical consequences of IAH/ACS and the association between CI and intra-abdominal pressure (IAP) among patients undergoing OR for ruptured AAA (rAAA), to compare extraluminal pHi monitoring, with standard intra-luminal monitoring among patients operated on for AAA, and to study the frequency and clinical consequences of IAH/ACS after endovascular repair (EVAR) for rAAA. The incidence of ACS was 26% in a retrospective study of 27 patients undergoing OR for rAAA. Consensus definitions on IAH/ACS were appropriate for patients after OR for rAAA: 78% (7/9) of patients with IAH grade III or IV developed organ failure and all patients who developed CI had some degree of IAH. Active fluid resuscitation treating hypovolaemia to avoid CI may partly cause IAH. The association between CI and IAP was investigated in a prospective study on 29 patients operated on for rAAA, 86% (25/29) were treated for hypovolaemia and ten (34%) had both IAH and CI. Since monitoring colonic perfusion is very important and there is no ideal method, a new technique, extraluminal colonic tonometry to detect colonic perfusion was compared with standard intraluminal tonometry. Although, this new method was not able to determine the severity of ischaemia it may serve as a screening test. EVAR of rAAA is feasible and patients may benefit from this less invasive procedure. Of 29 patients treated with this technique, 10% developed ACS, and all patients except one with preoperative shock developed some degree of IAH. In conclusion, IAP/ACS is common after both OR and EVAR for rAAA, and is associated with adverse outcome. Monitoring IAP and colonic perfusion with timely intervention may improve outcome.