En impesanteur réelle ou simulée, l'absence de gravité oriente les cellules souches multipotentes de la moelle osseuse à privilégier l’adipogénèse aux dépens de l’ostéogénèse. Ceci entraine une perte osseuse fréquemment rencontrée chez les astronautes lors des vols spatiaux. Parmi les traitements médicamenteux existants, le strontium possède une double action, à la fois activatrice de l'ostéogénèse et inhibitrice de l’adipogénèse. Dans ce contexte, l’objectif général de ce projet de thèse a été de démontrer que le strontium peut être un bon candidat pour contrecarrer les effets de l'impesanteur. Nous nous sommes particulièrement intéressés aux petites protéines Rho de la famille des GTPases, qui contrôlent le cytosquelette de la cellule, sa tension cellulaire ainsi que de nombreuses voies de signalisation. D'après la littérature, ces signalisations ont aussi été montrées comme étant liées aux voies du VEGF ou au statut oxydant des cellules, impliquées dans l’engagement des cellules souches multipotentes. La première partie de cette étude a permis de montrer l’effet antioxydant du strontium sur la lignée C3H10T1/2 en tant qu’activateur de la GTPase RhoA, permettant l’induction du gène clé de la réponse antioxydante, Nrf2, et par conséquent l’inhibition de l’adipogénèse. La deuxième partie a utilisé comme modèle des cultures 3D sur microbilles de polystyrène recouvertes de collagène pour la culture d'adipocytes, avec l'ajout de minéraux d’apatite pour la culture d'ostéoblastes. Ces billes ont été mises en culture dans un bioréacteur simulant l’impesanteur (Rotating Wall Vessel, RWV, NASA). Sous strontium, cette culture en RWV a favorisé l’ostéogenèse et limité l’adipogénèse, validant l'utilisation du strontium en tant que répresseur des effets délétères de l'impesanteur sur l’os. Nous avons montré que cet effet peut être expliqué d'une part par la stimulation des activités des deux GTPases RhoA et Rac1, et d'autre part par l’induction de l’isoforme matricielle du VEGF chez les ostéoblastes. En revanche, chez les adipocytes, les deux formes solubles et matricielles du VEGF étaient inhibées. De plus, le strontium a induit l'expression du récepteur Flt-1 qui favoriserait l’ostéogénèse. L’ensemble de ces données nous a permis de mieux comprendre les cinétiques de RhoA et Rac1 pendant l’ostéoblastogénèse et l’adipogénèse, ainsi que le rôle important des voies de signalisation du VEGF et du statut oxydant dans l’orientation de la différenciation des cellules multipotentes. Le strontium s’est révélé être un bon inducteur ostéogénique dont les applications fondamentales peuvent amener de nouvelles voies d’utilisation / In real or simulated microgravity, the absence of gravity directs multipotent stem cells from bone marrow to favor adipogenesis at the expense of osteogenesis. This causes a bone loss, commonly found in astronauts during spaceflight. Among existing drug therapies, strontium has a double action, both activating osteogenesis and inhibiting adipogenesis. In this context, the general objective of this project was to demonstrate that strontium may be a good candidate to counteract the microgravity effects. We were particularly interested in small proteins Rho of the GTPases family, which control cell cytoskeleton, cell tension and many signaling pathways. According to the literature, these pathways were also shown to be related to the VEGF singaling or the cell oxidative status, involved in the multipotent stem cells commitment. The first part of this study demonstrated the strontium antioxidant effect on the C3H10T1/2 line as an activator of the GTPase RhoA, allowing the induction of the key antioxidant response gene, Nrf2, and therefore inhibiting adipogenesis. The second part used a 3D cultures model on polystyrene microbeads coated with collagen for the adipocytes culture, and with mineral apatite added for osteoblasts culture. These beads were cultivated in a bioreactor simulating microgravity (Rotating Wall Vessel, RWV, NASA). With strontium, this RWV culture promoted osteogenesis and limited adipogenesis, validating the use of strontium as a repressor of the microgravity deleterious effects on bone. We have shown that this effect can be explained first by the stimulation of both GTPases RhoA and Rac1 activities, and secondly by the induction of the matrix-bound VEGF isoform in osteoblasts. In contrast, in adipocytes, both soluble and matrix-bound VEGF isoforms were inhibited. Moreover, strontium induced Flt-1 receptor expression, which would promote osteogenesis. All these data allowed us to better understand the RhoA and Rac1 kinetics during osteoblastogenesis and adipogenesis, and the important role of VEGF signaling pathways and oxidative status in directing multipotent cells differentiation. Strontium was found to be a good osteogenic inductor whose core applications can bring new ways of use

The diploma thesis is focused on the development of the concept of a mechanical device that would meet the necessary requirements to achieve a successful simulation of reduced gravity or microgravity on the tested body at its impact. The choice of a suitable mechanism is based on a literary research of all available variants and highlight of their specifics. Target values are created for the selected method of testing, upon reaching which the concept will be considered successful. In order to verify the functionality of the concept, a mechanism is assembled on a smaller scale. The individual components of the mechanism are tested and carefully selected. All essential physical processes taking place in the system are mathematically described and combined into a MATLAB script. A separate application is created to calculate the behavior of the system based on the specified input parameters.

Astronauts at are risk of losing 1.0-1.5% of their bone mass for every month they spend in space despite their adherence to high impact exercise training programs and diets high in nutrients, potassium, calcium, and vitamin D, all designed to preserve the skeletal system. This article reviews the basics of bone formation and resorption and details how exposure to microgravity or simulated microgravity affects the structure and function of osteoblasts, osteocytes, osteoclasts, and their mesenchymal and hematologic stem cell precursors. It details the critical roles that insulin-like growth factor-1 and its receptor insulin-like growth factor-1 receptor (GFR1) play in maintaining bone homeostasis and how exposure of bone cells to microgravity affects the function of these growth factors. Lastly, it discusses the potential of tumor necrosis factor-related apoptosis-inducing ligand, syncytin-A, sclerostin inhibitors and recombinant IGF-1 as a bone-saving treatment for astronauts in space and during their colonization of the Moon.

L’expérience I.C.E a pour objectif de tester le principe d’équivalence faible (WEP) à la base de la théorie de la relativité générale d’Einstein et postulant l’équivalence entre masse inertielle et masse grave. Si ce principe a toujours été vérifié jusqu’à aujourd’hui, il est d’un intérêt fondamental pour la physique moderne de poursuivre les mesures avec une précision accrue. En effet, de nouvelles théories d’unification de la mécanique quantique et de la relativité générale prévoient une violation de ce principe. Pour réaliser un test du WEP, il suffit de comparer les accélérations de deux objets en chute libre dans un même champ de gravitation, et c’est ce que réalise l’expérience I.C.E à l’échelle quantique (à la différence de la mission spatiale Microscope qui à ce jour a pu vérifier le WEP avec des objets macroscopiques avec une sensibilité sur le paramètre de 2.10−14). Ainsi, l’expérience consiste à réaliser, par une méthode interférométrique, la mesure de l’accélération de deux espèces atomiques (87Rb et 39K) de masses et de compositions différentes, en chute libre dans une enceinte à vide. La sensibilité de la mesure des effets inertiels auxquels les atomes sont sensibles (accélérations et rotations) est d’autant plus grande que la durée de chute libre des atomes est élevée et que la température des nuages est faible. Or, sur Terre au laboratoire, les atomes finissent par tomber au fond de l’enceinte les contenant sous l’effet de la gravité, ce qui limite grandement la sensibilité de la mesure. C’est pourquoi il est intéressant de placer l’expérience dans un environnement de micropesanteur dans lequel les atomes restent au centre de la chambre à vide afin d’atteindre des temps d’interrogation beaucoup plus longs. A ce titre, l’expérience est embarquée jusqu’à plusieurs fois par an, à bord de l’avion Zéro-g de la société Novespace. Les durées de micropesanteur proposées permettent d’atteindre des temps d’interrogation théoriques de l’ordre de la seconde ce qui doit porter le niveau de sensibilité à 10−11. Cependant, nous sommes aujourd’hui très fortement limités par le niveau élevé de vibrations et de rotations de l’avion : la perte de contraste des franges d’interférence engendrée ainsi que le bruit de phase introduit, ne nous permettent pas de dépasser des temps d’interrogation de 5 ms en 0 g. En parallèle, le laboratoire s’est récemment doté d’un simulateur de microgravité sur lequel est montée l’expérience, donnant accès à des temps d’interrogation de plus de 200 ms avec des trajectoires paraboliques d’une très bonne répétabilité (de l’ordre de 3 mg). La cohérence d’une source atomique étant directement reliée à sa température, l’utilisation de nuages ultra-froids est d’un grand intérêt pour améliorer le contraste des franges d’interférence, d’autant plus pour les longs temps d’interrogation visés. Le présent manuscrit synthétise les travaux ayant permis de produire le tout premier condensat de Bose-Einstein (la source atomique ultime) de 87Rb en microgravité par une méthode tout optique, et ce, de manière répétable toutes les 13,5 secondes. Nous démontrons l’efficacité de note méthode de chargement du piège dipolaire basée sur l’association d’un refroidissement par mélasse grise et d’une modulation spatiale des faisceaux dipolaires. Ces résultats ouvrent la voie vers de futures mesures interférométriques très sensibles à grand facteur d’échelle. / The I.C.E experiment aims at testing the weak equivalence principle (WEP) underlying Einstein’s theory of general relativity and which postulates the equivalence between inertial mass and gravitationnal mass. If this principle has always been verified until today, it is of fundamental interest for physics to continue the measurements with greater precision. Indeed, new unifying theories of quantum mechanics and general relativity predict a violation of this principle. To carry out a test of the WEP, it suffices to compare the accelerations of two objects in free fall in the same gravitationnal field. This is what the I.C.E experiment, on the quantum scale, achieves (unlike the spatial Microscope mission, which to date has been able to verify the principle of equivalence with macroscopic objects with a sensitivity on of 2.10−14). Thus, the experiment consists in performing, by an interferometric method, the measurement of the acceleration of two atomic species (87Rb and 39K) of different mass and composition in free fall in a vacuum chamber. The measurement sensitivity of the inertial effects to which the atoms are sensitive (accelerations and rotations) is all the greater as the free fall time of the atoms is high and their temperature is low. But on Earth, in the laboratory, the atoms eventually fall to the bottom of the vacuum chamber containing them under the effect of gravity, which greatly limits the measurement sensitivity achievable. This is why it is interesting to place the experiment in a microgravity environment in which the atoms stay in the center of the vacuum chamber in order to reach much longer interrogation times. As such, several times a year, the experiment is put aboard the aircraft Zero-g of the Novespace company. The available microgravity durations make it possible to reach theoretical interrogation times of the order of one second, which should raise the sensitivity level to 10−11. However, we are today very strongly limited by the high level of vibrations of the aircraft as well as its rotations : the loss of contrast of the interference fringes and the phase noise caused, do not allow us to exceed 5 ms of interrogation times in 0 g. Since the coherence of an atomic source is directly related to its temperature, the use of ultra-cold clouds is of great interest to improve the contrast of the interference fringes, especially for the long interrogation times targeted. In parallel, the laboratory is now equipped with a microgravity simulator on which is mounted the experiment, giving access to interrogation times of more than 250 ms with parabolic trajectories of a very good repeatability (of the order of 3 mg). This manuscript synthesizes the work that produced the very first 87Rb Bose-Einstein condensate in microgravity by all-optical methods, with a repetition rate of 13,5 seconds. We demonstrate the efficiency of our dipole trap loading method based on the association of a grey molasses cooling and a spatial modulation of the dipole beams. These results pave the way for future highly sensitive interferometric measurements with a large scale factor.

In order to enhance accessibility to microgravity research, the design process for experiments on the ISS must be streamlined and accessible to all scientific disciplines, not just aerospace engineers. Thus, a general design and analysis toolbox with accompanying best practices manual for microgravity liquid containment is proposed. The work presented in this thesis improves the design process by introducing a modular liquid tank design which can be filled, drained, or act as a passive liquid-gas separation device. It can also be pressurized, and used for aerosol spray. This tank can be modified to meet the design requirements of various experimental setups and liquids. Furthermore, rough simulations of this tank are presented and available to the user for modification. The simulation and design methodology for other general cases is discussed as well. After reading this thesis, the user should have a basic understanding of how liquids behave in microgravity. She will be able to run simple simulations, design, build, test, and fly a liquid management device which has been modified to suit the requirements of her specific experiment. The general tank design can be manufactured using 3-D printing, traditional CNC milling, or a combination thereof. The design methodology and best practices presented here have been used to design tanks used in experiments on the International Space Station for Budweiser and Lambda Vision. Both tanks functioned nominally on orbit. While the specific data from these experiments cannot be presented due to proprietary restrictions, using this thesis as a design guide for new experiments should yield favorable results when applied to new tank designs. If the reader has any questions or would like an updated design process, the author’s preferred contact information can be found using the Orcid iD: 0000-0002-2617-2957 .

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This dissertation aims to better understand the evolution of single hydrogen gas bubbles evolved during the water electrolysis at microelectrodes. In particular, the growth and detachment processes were studied in detail experimentally by means of electrochemical and optical methods in terrestrial, micro-, and hypergravity conditions. The combination of microelectrode and sulfuric acid promoting the bubble coalescence results in a periodical growth and the detachment of single bubbles. This provides a systematic view on the phenomena under study. A shadowgraphy system was used to provide general insight into the bubble behaviour, while Particle Tracking Velocimetry (PTV) was used for the flow velocity measurements around the growing hydrogen bubble. By applying high electric potentials considerably exceeding that in industrial electrolysers, it is possible to analyse the evolution of hydrogen bubbles under extreme conditions and for a wide range of electrolyte concentrations, overall shedding more light on bubble dynamics in general, and especially the underlying balance of forces. The growth of single hydrogen bubbles at micro-electrodes was studied in an acidic electrolyte over a wide range of concentrations and cathodic potentials. New bubble growth regimes were identified which differ in terms of whether the bubble evolution proceeds in the presence of a monotonic or oscillatory variation in the electric current and a carpet of microbubbles underneath the bubble. Key features such as the growth law of the bubble radius, the dynamics of the microbubble carpet, the onset time of the oscillations and the oscillation frequencies were characterised as a function of the concentration and electric potential. Furthermore, the system's response to jumps in the cathodic potential was studied. The electrode, tilted to the horizon, promotes faster growth and, therefore, earlier detachment at the smaller volume of the bubble. During its evolution, the bubble moves laterally from the electrode centre, releasing the electrode area and enabling higher electric current, therefore faster hydrogen generation and bubble-bubble coalescence rates. The duration of the bubble position oscillations found on the horizontal electrode gradually reduces upon tilt angle increase, with an almost complete disappearance at 5°. Based on the analysis of the forces involved and their scaling with the concentration, potential and electric current, a sound hypothesis was formulated regarding the mechanisms underlying the micro-bubble carpet and oscillations. A detailed look was also taken on the dynamics of single hydrogen bubbles in microgravity during parabolic flights. Three bubble evolution scenarios were identified depending on the electric potential applied and the acid concentration. The dominant scenario, characterised by lateral detachment of the grown bubble, was studied in detail. For that purpose, the evolution of the bubble radius, electric current and bubble trajectories as well as the bubble lifetime were comprehensively addressed for different potentials and electrolyte concentrations. The bubble-bubble coalescence events, which are responsible for reversals of the direction of bubble motion, were particularly analysed. Finally, as parabolic flights also permit hypergravity conditions, a detailed comparison of the characteristic bubble phenomena at various levels of gravity was drawn. Finally, the Marangoni convection at the foot of hydrogen gas bubbles mainly induced by the thermocapillary effect is systematically studied during the bubble evolution, the bubble position oscillations, at horizontal and tilted electrodes both in terrestrial and hyper-g environments. The flow structure progressively modifies with the bubble evolution or during the bubble position oscillations, i.e. as per electric current and bubble geometry variation. The velocity increases both with the bubble size and the electric current magnitude. It reaches up to 50 mm/s and 125 mm/s shortly before the bubble detachment at horizontal and tilted electrodes, correspondingly. The bubble position oscillations characterised by the large variation of the electric current govern the velocity of around ~80 mm/s at the highest and ~40 mm/s at the lowest positions. In the case of tilted electrodes, both in terrestrial and hyper-g environments, the lateral movement of the bubble enables higher values of the current and, therefore, stronger convection. The non-homogeneous distribution of the electric current lines at the tilted electrode results in the asymmetrical Marangoni convection around the bubble. There is a certain limitation in terms of the maximal magnitude of the velocity at different tilt angles, governed by the optimal size of the bubble and electric current. At last, the effects of the particles and laser used for PTV measurements were shown to reduce the duration of the oscillations and to retard the bubble evolution. Both effects were considered during the measurements.

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