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Le présent travail de Doctorat porte sur l’adaptation et le déconditionnement cardiovasculaire chez l’astronaute en microgravité réelle prolongée, en microgravité simulée de courte durée (avec et sans contremesures par hypergravité), et en confinement de longue durée. Afin de répondre à cette thématique, 3 études expérimentales sur l’humain ont été réalisées, et de fait, ce présent travail de Doctorat se divise en 3 parties distinctes. La première est la mission « Mars 500 » qui comprend un confinement de 520 jours de 6 sujets-volontaires. La seconde est le projet « Vessel Imaging » qui comprend un vol spatial respectif de 6 mois à bord de la « Station Spatiale Internationale (ISS) » de 10 sujets-astronautes. La troisième est l’étude «Short Time Bed-Rest (STBR)» (12 sujets) qui comprend une courte période de microgravité simulée par alitement prolongé à -6° (5 jours) avec et sans l’utilisation de deux contremesures cardiovasculaires par hypergravité (continue ou intermittente). / This PhD work focuses on astronaut cardiovascular adaptation and deconditioning in real prolonged microgravity, short simulated microgravity (with and without countermeasures) and long-term confinement. To answer to this topic 3 humans experimental studies have been performed, and thus the present PhD work is divided into 3 distinct parts . The first one is the mission « Mars 500 » which consists in 520-days confinement with 6 subjects-volunteers mission. The second is the project « Vessel Imaging » whitch consit in a 6-months spaceflight aboard the « International Space Station » with 10 subjects-astronauts. The third is the « Short Time Bed -Rest (STBR) » study (12 subjects) which consist in a short period of bedrest (-6°, 5 days) with and without the use of two cardiovascular countermeasures by hypergravity (continuous or intermittent).

Master of Science / Department of Kinesiology / Thomas J. Barstow / Background and Aim: Long-term microgravity exposure, via spaceflight or -6° head-down tilt bedrest, has been shown to produce significant cardiovascular deconditioning and decreases in exercise performance. However, there is little known about how acute microgravity exposure influences the cardiovascular system’s ability to adjust to increases in physical work. Therefore, the aim of this study was to compare cardiovascular and exercise performance during acute upright, supine and -6° head-down tilt positions. Methods: Seven healthy inactive men performed maximal cycle exercise (VO2peak) tests in the upright, supine, and -6° head-down tilt on separate days. Oxygen consumption and heart rate were measured continuously throughout the testing procedures. Cardiac output (acetylene exhalation technique) was measured periodically and interpolated to the 100-watt work rate. Stroke volume was calculated from cardiac output and heart rate data. Results: Peak oxygen uptake and heart rate were significantly decreased in the supine and -6° head-down tilt positions compared to the upright (VO2peak 2.01±0.46, 2.01±0.51 versus 2.32±0.61 L/min respectively; peak heart rate 161±13, 160±14 versus 172±11 bmp). However, cardiac output at 100-watts was similar in all three-exercise positions. Calculated stroke volume at 100-watts was significantly higher in the -6° head-down tilt position compared to the upright position (76.6±4.7 versus 71.2±4.5, ml). Conclusion: These results suggest that exercise capacity is immediately decreased upon exposure to a microgravity environment, prior to any cardiovascular deconditioning. Therefore, an astronaut’s exercise performance should be evaluated with exercise tests in the -6° head-down tilt position prior to space flight in order to establish a baseline response.

This thesis entails a detailed microstructure analysis of directionally solidified (DS) Al-7Si alloys processed in microgravity aboard the International Space Station and similar duplicate ground based experiments at Cleveland State University. In recent years, the European Space Agency (ESA) has conducted experiments on alloy solidification in microgravity. NASA and ESA have collaborated for three DS experiments with Al- 7 wt. % Si alloy, aboard the International Space Station (ISS) denoted as MICAST6, MICAST7 and MICAST12. The first two experiments were processed on the ISS in 2009 and 2010. MICAST12 was processed aboard the ISS in the spring of 2014; the resulting experimental results of MICAST12 are not discussed in this thesis. The primary goal of the thesis was to understand the effect of convection in primary dendrite arm spacings (PDAS) and radial macrosegregation within DS aluminum alloys. The MICAST experiments were processed with various solidification speeds and thermal gradients to produce alloy with differences in microstructure features. PDAS and radial macrosegregation were measured in the solidified ingot that developed during the transition from one solidification speed to another. To represent PDAS in DS alloy in the presence of no convection, the Hunt-Lu model was used to represent diffusion-controlled growth. By sectioning cross-sections throughout the entire length of solidified samples, PDAS was measured and calculated. The ground-based (1-g) experiments done at Cleveland State University CSU were also analyzed for comparison to the ISS experiments (0-g). During steady state in the microgravity environment, there was a reasonable agreement between the measured and calculated PDAS. In ground-based experiments, transverse sections exhibited obvious radial macrosegregation caused by thermosolutal convection resulting in a non-agreement with the Hunt- Lu model. Using a combination of image processing techniques and Electron Microprobe Analysis, the extent of radial macrosegregation was found to be a function of processing conditions and PDAS.

Quel rôle joue la gravité dans les représentations internes de l'action ? Au-delà des contraintes d'équilibre, le vecteur gravitaire influence-t-il l'action de façon globale, jusqu'à la perception des mouvements de nos semblables ? Ces questions ont été celles qui ont guidé mes travaux de thèse. L'originalité de notre approche a été de placer l'exécution et la perception de l'action dans un « continuum fonctionnel » s'articulant autour des représentations internes de l'action. Pour ce faire, l'outil de choix qui est commun aux trois expériences de cette thèse est la microgravité (0G). Les expériences de cette thèse ont montré que les représentations internes de l'action se nourrissaient des informations graviceptives pour se construire et s'adapter constamment. Cependant, dans certaines conditions telle que la 0G à court terme, apparaît un ordre de priorité. En effet, le SNC est capable de mettre en place des solutions immédiates et efficaces pour l'exécution, comme en témoigne la repondération sensorielle rapide qui s'opère en 0G dans une tâche d'orientation posturale. Cependant, un temps de latence est observé dans la recalibration des modèles internes sur la base des afférences sensorielles fortement perturbées. C'est ce que nous avons montré grâce à un protocole d'imagerie motrice, mettant en évidence une perte de l'isochronie entre les mouvements exécutés et imaginés en 0G. Enfin, nous avons mis en évidence, chez des sujets sans expérience aucune de microgravité, que la perception du mouvement humain est efficace même lorsque ce dernier est exécuté en apesanteur, bien que des réseaux cérébraux différents soient mis en jeux. / What is the role of gravity in the internal representations of action? Beyond the constraints of balance, does the gravity vector influence the action globally, up to the perception of our peers' movement? These issues have guided my thesis work. The originality of our approach was to place the execution and the perception of action in a "functional continuum" built around the internal representations of the action. To do this, the tool of choice, that is common to all three experiments presented here, is microgravity (0G). The experiments of this thesis showed that the internal representations of action are fed with graviceptive information to build and adapt constantly. However, under certain conditions such as short-term 0G, an order of priority appears. Indeed, the CNS is able to implement immediate and effective solutions, as we demonstrate it with the fast sensorial reweighting observed during a postural orientation task. However, a lag is observed in the recalibration of internal models based on sensory inputs severely disrupted. This is what we have shown through a protocol of motor imagery, showing a loss of isochrony between executed and imagined movements under 0G. Finally, we have demonstrated in subjects without any experience of microgravity, that the perception of human movement is effective even when it is performed in weightlessness, although different cerebral networks are involved.

The impact of gravity on organic material such as the human body has been a growing research field ever since the dawn of space flight. The Random Positioning Machine (RPM) is used to simulate microgravity on organisms without the use of real microgravity that is both expensive and scarcely available. This enables in-depth studies on the effect of weightlessness on organic materials in a controlled environment with relatively small means. The RPM has not yet been commercialized to a broader market but the most recent improvements to the machine creates possibilities for a start-up business revolving around the RPM. A method including both qualitative and quantitative models based on a case study were used to capture both aspects and to understand both how far in development the technologies were and the potential in the different market segments. The TRL for the different UVP’s of the RPM were generally ranked high except for the modularity and the market segment ranking shows that, from the four chosen segments, the food fermentation and fat crystallization segments have the most potential. The watch industry showed a minimal amount of potential. The SWOT-analysis on the two segments shows that the biggest weakness is the inexperience with start-ups but that is countered by the possibility for support by the university. For the food fermentation, there is an opportunity for a partnership where the company Swiss Culture Collection has shown interest in cooperation but there is also the threat of end customers equating organisms produced in microgravity with GMO, and by that having a negative impact. For fat crystallization, there is an opportunity with improving the process for producing low-fat products if research shows that microgravity can affect the density of the product. On the other hand, there is a lot of research that needs to be done to get the results.

Les vols spatiaux affaiblissent le système immunitaire. Les objectifs de cette thèse étaient de déterminer, à l’aide de modèles terrestres, les conséquences d’une exposition à la micropesanteur simulée, l’hypergravité ou des stress chroniques ultra légers sur l’immunité humorale murine. Nous avons ainsi montré que la suspension anti-Orthostatique, qui mime certains effets de la micropesanteur, induit une diminution de 59% du nombre de lymphocytes B spléniques et une inversion du rapport entre lymphocytes B et T. L’affaiblissement de la lymphopoïèse B mis en évidence par la diminution du nombre de progéniteurs lymphoïdes et des cellules pré-B en est probablement la cause. De plus, la position anti-Orthostatique entraîne, en l’absence de stress, une diminution de la réponse in vitro des lymphocytes B au LPS, plus importante que celle des lymphocytes T à la ConA, comme en hypergravité. Afin de déterminer les mécanismes responsables de la diminution de la réponse des lymphocytes B chez les souris hypergravitaires, les transcrits de gènes impliqués dans la voie TLR-4, le récepteur du LPS, ont été quantifiés. L’expression de plusieurs gènes de la voie MyD88-Dépendante est augmentée après 21 jours d’hypergravité, mais aucune modification n’a été observée dans les lymphocytes B stimulés avec du LPS. Enfin, la contribution de stress chroniques ultra légers a été évaluée. Les proportions de lymphocytes spléniques ne sont pas affectées par ces stress. Par contre, le taux d’IgA sériques s’est révélé augmenté et une baisse des cytokines pro-Inflammatoires de type Th1 a été observée comme chez les astronautes. Ainsi, ces stress n’expliquent pas complètement l’impact négatif des vols spatiaux sur l’immunité humorale. Ces recherches sont importantes pour identifier la/les cause(s) de l’altération de l’immunité humorale en vol, afin de tester/développer des contremesures efficaces pour renforcer le système immunitaire des astronautes, mais également de personnes stressées ou âgées / Spaceflight weaken the immune system. The aims of this thesis were to determine the effects of exposure to simulated microgravity, hypergravity or chronic ultra-Mild stress on murine humoral immunity, using ground-Based models. We were able to show that the anti-Orthostatic suspension, that mimics some of the effects of microgravity, caused a 59% decrease of the number of splenic B cells and an inversion of the ratio between B and T lymphocytes. A decrease in B lymphopoiesis, as evidenced by the decrease of lymphoid progenitors and pre-B cells is likely the cause. Furthermore, we showed that the anti-Orthostatic position, in the absence of stress, leads to a decreased in vitro response of B cells to LPS, more important than the one of T cells to ConA, as did hypergravity exposure. To determine the mechanisms responsible of the decreased response of B cells from hypergravity mice, transcripts encoding genes involved in the TLR-4 signaling pathway, the LPS receptor on B cells, have been quantified. The expression of several genes of the MyD88-Dependent pathway was increased after 21 days of hypergravity, but no change was observed in B cells stimulated with LPS. Finally, the contribution of chronic ultra-Mild stresses was evaluated. The proportions of splenic lymphocytes were not affected by these stresses. However, the levels of serum IgA were increased and those of Th1 pro-Inflammatory cytokines were decreased, as in astronauts. Thus, these stresses do not fully explain the negative impact of spaceflight conditions on humoral immunity. These researches are important to identify the cause(s) of spaceflight-Associated impaired immunity in order to test/develop effective countermeasures to strengthen the immune system of astronauts, but also of stressed or elderly people

"The condensation of vapor onto a cooled surface is a phenomenon which can be difficult to quantify spatially and as a function of time; this thesis describes an ultrasonic system to measure this phenomenon. The theoretical basis for obtaining condensate film thickness measurements, which can be used to calculate growth rates and film surface features, from ultrasonic echoes will be discussed and the hardware and software will be described. The ultrasonic system utilizes a 5MHz planar piston transducer operated in pulse-echo mode to measure the thickness of a fluid film on a cooled copper block over the fluid thickness range of 50 microns to several centimeters; the signal processing algorithms and software developed to carry out this task are described in detail. The results of several experiments involving the measurement of both non-condensing and condensing films are given. In addition, numerical modeling of specific condensate film geometries was performed to support the experimental system; the results of modeling nonuniform fluid layers are discussed in the context of the effect of such layers on the measurement system."

La croissance et le détachement des bulles formées sur une paroi par injection ou ébullition sont présents dans de nombreuses situationsindustrielles (les contacteurs gaz/liquide, les évaporateurs ou des dispositifs d’impression à jet d’encre). Dans la plupart des applications, les bulles grossissent dans un écoulement cisaillé ou au repos et la plupart des études visent à prévoir le rayon de détachement par une analyse de l’équilibre des forces. Ainsi, une bonne modélisation des forces capillaires et hydrodynamiques est nécessaire pour prédire correctement le rayonau détachement. Dans un premier temps, la croissance quasi-statique d’une bulle d’air formée sur la paroi d’une cuve et d’un canal rectangulaire est étudiée. Trois substrats différents sont utilisés pour observer l’influence des conditions de mouillage. La dynamique de la croissance de la bulle et le détachement sont alors enregistrés différentes configurations : canal horizontal, canal incliné, avec et sans écoulement liquide. Ensuite,le comportement des bulles de vapeurs en croissance sur une paroi en ébullition en vase et convective est étudié. Les expériences sonteffectuées en gravité terrestre et en microgravité dans un liquide sous-refroidi (HFE 7000) à basse pression (1-2bars). Des bulles de vapeurssont nuclées sur la paroi par l’intermédiaire d’un générateur de bulles. Ce dernier chauffe le liquide environnant au-dessus de sa température de saturation. Les bulles croient sur le site de nucléation dans un écoulement cisaillé et se détachent soit directement soit en glissant le long de la paroi. Une copie de la cellule d’essai appelée RUBI développée par l’ESA est implémentée dans le dispositif expérimental pour effectuer lespremières expériences en microgravité avant son lancement dans la station spatiale ISS. Toutes les acquisitions sont filmées à l’aide d’une caméra rapide et l’extraction du contour de la bulle est réalisée par traitement d’images. Différentes forces agissant sur une bulle sont calculées à partir des paramètres géométriques de la bulle. Un modèle prédictif de détachement de bulles est proposé. Enfin, un bilan thermique diphasique est effectué. / The growth and departure of bubbles nucleated on a wall are of particular interest in industrial situations such as gas/liquid contactors in chemicalprocessing, vapor nucleation in evaporators or inkjet printing devices. In most of these industrial applications, the bubbles grow in a shear flow and most studies aim topredict the radius at detachment by a force balance analysis. Thus a good modeling of both the hydrodynamic and capillary forces is needed to predict correctly this radius. First, the quasi-static growth of an air bubble nucleated on the wall of a tank and a rectangular channel is investigated. Three different substrates are used to observe the wettability effect. The dynamics of the bubble growth and detachment is then recorded for different configurations : horizontal channel, inclined channel, with and without a shear flow. Then, behavior of vapor bubbles growing at a wall in pool boiling and flow boiling is investigated. Experiments are performed in normal and microgravity environments with a subcooled test liquid HFE-7000 at low pressure (1-2 bars). Vapor bubbles are nucleated on the wall by a bubble generator that heats the liquid above its saturation temperature. This bubble generator was designed to provide nucleation on an isolated site. These bubbles grow on this nucleation site under an imposed shear flow and depart downstream either along the wall or perpendicularly. A copy of the test cell called RUBI developed by ESA is included in our experiment to perform the first experiments in microgravity before its launch to the ISS. Geometric and kinematic features of the air bubbles and vapor bubblesare measured by processing images obtained by high-speed video recordings. Different forces acting on the bubbles are calculated from these measurements, using a point force approach. The validity of this mechanistic approach to the bubble dynamics is discussed. At last, heat transfer balance is estimated on the bubble.

Experiments with microbial biofilms in microgravity and simulated microgravity have revealed altered growth kinetics, but geomicrobial biofilms have not yet been studied in low gravity environments. No characterisation of biofilms, geomicrobial or otherwise, have been conducted at hypergravity. This thesis explores factors affecting microbe-mineral interactions under terrestrial conditions, lays the groundwork for a scheduled microgravity experiment, and provides the first data on biofilms grown at hypergravity. As a first step in understanding microbe-mineral interactions in altered gravity environments, experiments were undertaken to identify factors that constrain attachment in a terrestrial environment. The model organism Sphingomonas desiccabilis and basaltic rock from Iceland were selected, and the minerals that make up the basalt were identified and procured in their pure form. The relative significance of physical factors such as hydrophobicity, surface charge, porosity and nutritional value were examined in relationship to the success with which biofilms colonised the mineral surfaces. Growth was measured by the quantity of biofilm biomass after a ifxed time period, using Crystal Violet stain, in order to draw conclusions about the most influential physical conditions on biofilm attachment to a substrate. It was found that mineral attachment is influenced more by porosity and nutritional value than by hydrophobicity or surface charge. To explore how reduced gravity affects biofilm formation and weathering rates, a European Space Agency experiment, BioRock, is underway. Samples of basalt, with monocultures of three different organisms, will be sent to the International Space Station in 2019 for long-term exposure to Martian and micro-gravity. Research testing proof of concepts, material compatibility, and experimental procedure and equipment is described. Confocal laser scanning microscopy (CLSM) was used to image the biofilms, and inductively coupled plasma mass spectroscopy (ICP-MS) experiments were conducted to compare biotic and abiotic elemental release rates from basalt. Both of these methods will be employed for post-flight analysis of BioRock. Preliminary terrestrial ICP-MS experiments indicated that rare Earth elements (REEs) showed the most reliable reflection of leaching patterns overall, as a consequence of their high molecular weight and low volatility during the ashing procedure. To fully understand gravity's effect on microbiological processes it is important to investigate what occurs when its influences are removed, but also to establish what occurs when extra gravitational force is applied. Using simulated hypergravity, achieved through hyper-acceleration on a geotechnical centrifuge, the effects of 10 x g on biofilm development and the leaching of basalt were investigated. As this was the first time that biofilms had been studied under hypergravity, additional substrates were included with the basalt, to enable characterisation of the more general response of biofilms to hypergravity. In contrast to previous experiments conducted on planktonic bacteria, which found decreased population sizes, the biofilms grown at 10 x g showed greater biomass than the 1 x g samples. ICP-MS showed no difference in the average weathering rates, but greater variability in the higher gravity samples. The data collected here advances our understanding of microbial interactions with geologically important substrates, with implications for an ISS microgravity experiment and future human space exploration. It also presents new intelligence on the previously unstudied effects of hypergravity on biofilms and rock weathering.