Quiescence is a non-proliferative cellular state that is critical to tissue repair and regeneration. Although often described as the G0 phase, quiescence is not a single homogeneous state. As cells remain quiescent for longer durations, they move progressively deeper and display a reduced sensitivity to growth signals. Deep quiescent cells, unlike senescent cells, can still re-enter the cell cycle under physiological conditions. Mechanisms controlling quiescence depth are poorly understood, representing a currently underappreciated layer of complexity in growth control. Here, we show that the activation threshold of a Retinoblastoma (Rb)-E2F network switch controls quiescence depth. Particularly, deeper quiescent cells feature a higher E2F-switching threshold and exhibit a delayed traverse through the restriction point (R-point). We further show that different components of the Rb-E2F network can be experimentally perturbed, following computer model predictions, to coarse-or fine-tune the E2F-switching threshold and drive cells into varying quiescence depths.

[pt] Estruturas reticuladas espaciais com grandes vãos são encontradas em uma variedade de aplicações em engenharia. Muitas dessas estruturas apresentam um comportamento eminentemente não linear, envolvendo tanto não linearidades físicas quanto geométricas, o que leva em muitos casos a múltiplas configurações de equilíbrio. Em particular, estruturas biestáveis estão usualmente sujeitas a instabilidades por ponto limite (snap-through), bifurcações simétrica instável ao longo do caminho não linear de equilíbrio, instabilidade elástica de elementos individuais, devido à plastificação destes elementos ou a interação destes fenômenos. O presente trabalho tem como objetivo a análise detalhada de duas classes de estruturas biestáveis: treliças piramidais (instabilidade indesejada) e estruturas ajustáveis com elementos de tesoura (instabilidade desejada). Ferramentas teóricas e computacionais são desenvolvidas para a investigação da influência das medidas de deformação quadrática e logarítmica, deformações elasto-plásticas e instabilidades na resposta estática e dinâmica não linear de um módulo de treliça piramidal. Uma formulação corrotacional em elementos finitos é proposta para descrever a ligação espacial flexível encontrada nas estruturas ajustáveis biestáveis aqui estudadas. A análise de estruturas com grandes vãos formadas pela junção de módulos de treliças piramidais ou módulos ajustáveis é apresentada. Os resultados obtidos mostram que a presença e interação das diversas fontes de instabilidade têm uma grande influência no comportamento destas estruturas e pode determinar ou não a sua viabilidade em aplicações práticas. / [en] Large span reticulated structures are applied in a variety of engineering applications. Many of these structures present a nonlinear behavior involving both geometric and material nonlinearities with multistable configurations. Particularly, bistable structures are often subjected to instability phenomena, such as snap-through and bifurcations of the whole structure, individual units or single bars. The present work, focuses on two classes of bistable structural systems: pyramidal trusses (undesired instability) and deployable scissor structures (desired design instability). Theoretical and computational tools are developed to investigate the influence of the strain measure, elasto-plastic deformations and instability phenomena on the nonlinear static and dynamic response of bistable pyramidal trusses. A compliant corrotational spatial joint finite element formulation with finite size is developed and applied to study bistable deployable scissor modules. The analysis of bistable large span structures formed by the assembly of modules is also carried out. It s shown that the presence and interaction of the studied buckling sources have deep influence on the systems behavior and can ultimately determine their viability in practical applications.

L’objectif de cette thèse est d’explorer le contrôle de processus électroniquement induits dans diverses molécules fonctionnalisées adsorbées sur la surface du Si(100). Ce travail s’inscrit dans le contexte des nanosciences moléculaires et a été réalisé à l’aide d’un microscope à effet tunnel (STM) à basse température (9K). Nous avons utilisé une approche combinant étude statistique et modélisation théorique afin de pouvoir explorer la physique des divers processus observés. Cette thèse débute par l’étude de la molécule d’hexaphényle benzène (HPB) dont les phényles latéraux permettent un découplage électronique entre la molécule et la surface du silicium. Grâce à cet effet, nous avons pu contrôler la diffusion directive et réversible de la molécule d’HPB physisorbée le long des marches de type SA à la surface du Si(100)−2×1 à travers un processus combinant l’action des électrons tunnels et celle du champ électrostatique induit par la pointe du STM. Ces premiers résultats ont permis d’envisager l’étude d’un couple de molécules de tétraphényles porphyrines métalliques adsorbées à la surface du Si(100)−2×1. Il s’agit de NiTPP et de CuTPP qui, comme pour l’HPB, possèdent des cycles phényles latéraux. Plusieurs conformations d’adsorption de ces deux molécules ont été caractérisées et leurs réponses à des excitations électroniques étudiées. Ceci nous a permis, pour la molécule de NiTPP, d’aboutir au contrôle de l’activation réversible d’un bistable intra-moléculaire en dépit de la chimisorption partielle de la molécule sur le silicium. L’étude de la molécule de CuTPP, quant à elle, montre des courbes de conductance I(V) en forme d’hystérésis associées à des changements réversibles de conformations réalisant ainsi une fonction mémoire. Dès lors, nous avons pu étudier la co-adsorption des molécules de NiTPP et de CuTPP sur le Si(100) afin de réaliser un binôme moléculaire. Divers couples de molécules ont pu être étudiés. Sur l’un d’entre eux, nous avons pu activer des processus d’excitations inter-moléculaires en excitant électroniquement l’une des molécules afin d’observer un changement de conformation de la seconde molécule du binôme. Ce résultat réalise ainsi le contrôle électronique d’un dispositif bi-moléculaire en s’affranchissant des processus électroniques induits via le substrat. Enfin, à titre de perspective, ce travail de thèse présente un procédé novateur permettant le contrôle local de l’hydrogénation de la surface de Si(100). Ceci est réalisé grâce à la passivation de la pointe du STM par l’hydrogène moléculaire à 9K. Les électrons tunnels sont ensuite utilisés pour induire la dissociation intra-dimer des molécules d’H2 sur la surface du Si(100). Cette technique peut être envisagée pour la passivation du Si(100) ou pour agir localement sur des circuits moléculaires. / The objective of this thesis is to explore the control of electronically induced processes in various functionalized molecules adsorbed on the surface of silicon (100). In the context of molecular nanoscience, this work has been carried out using a scanning tunneling microscope operating at low temperature (9K). We used an approach combining statistical study and theoretical modelling in order to explore the physics of the various observed processes. This thesis begins with the study of the Hexaphenylbenzene (HPB) molecule for which the lateral phenyl rings enable the molecule-silicon surface electronic decoupling. Thanks to this effect, we could achieve a directive and reversible diffusion control of physisorbed HPB molecules along the SA silicon step edge through a process combining the joint actions of tunnel electrons and the local STM tip induced electrostatic field. These first results allowed considering the study of a couple of metaltetraphenyl porphyrin molecules adsorbed on the Si(100)-2x1 surface. Similarly to the HPB molecules, the two chosen metalloporphyrins: NiTPP and CuTPP, have lateral phenyl rings. Several adsorption conformations for these molecules were characterized and their response to electronic excitation has been studied. In the case of NiTPP, this led to the control of the reversible activation of an intra-molecular bistable despite the partial chemisorption of the molecule on the silicon surface. As for CuTPP molecule, our study revealed hysteresis behavior on the I(V) conduction curves associated with reversible conformation changes which represents the realization of a memory function. Following the study of each molecule apart, we performed the co-adsorption of the two molecules on the Si(100) surface to study molecular pairs. Various pairs of molecules have been studied. On one of them, we were able to activate an inter-molecular excitation transfer process by locally exciting one molecule and observing a conformation change of the second molecule of the pair. This result thus shows the electronic control of a bi-molecular device getting rid of substrate mediated electronic process. Finally, as a perspective, this thesis presents a novel technique allowing the controlled local hydrogenation of the Si(100) surface. This is achieved thanks to the passivation of the STM tip by molecular hydrogen at 9K. The tunnel electrons are then used to induce the intra-dimer dissociative adsorption of H2 molecules on the Si(100) surface. This technique could be considered for the passivation of Si(100) or to locally modify molecular circuits.

Cette thèse concerne la récupération d'énergie vibratoire dans le but de proposer une alternative aux batteries conventionnelles pour l’alimentation de systèmes autonomes sans fil. Ceci permettrait d’améliorer leur compacité (moins d’énergie stockée), leur tenue dans des environnements sévères (forte température) et de réduire leur besoin d'entretien. Cette étude se concentre plus particulièrement sur les générateurs oscillants bistables, intéressants pour leur grande plage de fréquences utile comparée à celle offerte par les générateurs linéaires (limitée à la zone de résonance). Cette thèse se divise en quatre grandes parties. La première présente la construction du modèle mathématique permettant de prédire les différents comportements du générateur bistable (ces derniers pouvant coexister sur certaines plages de fréquences) incluant l'étude de la stabilité aux petites perturbations. Ce modèle met en évidence des comportements du générateur encore peu exploités pour la récupération d'énergie : les comportements sous-harmoniques dont la plage de fréquences permet d'agrandir la bande passante globale du générateur. Afin d’améliorer la précision du modèle, celui-ci est ensuite complété dans la deuxième partie par un critère semi-analytique : le critère de robustesse de stabilité qui caractérise la sensibilité du générateur aux perturbations extérieures (plus un comportement est robuste plus il sera facile à maintenir dans le temps). Le modèle ainsi obtenu ainsi que le système expérimentale montrent une grande plage de fréquences sur laquelle coexistent des comportements intéressants pour la récupération d’énergie (les orbites hautes) et des comportements non désirables (les orbites basses). La troisième partie de cette thèse présente donc différentes stratégies permettant de sauter des orbites basses vers les orbites hautes en jouant directement sur les paramètres du générateur. Enfin, la quatrième et dernière partie s’attarde sur l’influence du circuit d'interface AC-DC entre le générateur bistable et la charge en vue de son intégration future. / This thesis concerns vibratory energy harvesting in order to propose an alternative to conventional batteries for the power supply of autonomous wireless systems. This would improve their compactness (less stored energy), their resistance to harsh environments (high temperature) and reduce their need for maintenance. This study focuses in particular on bistable oscillating generators, which are interesting for their large useful frequency range compared to that offered by linear generators (limited to the resonance zone). This thesis is divided into four main parts. The first presents the construction of the mathematical model to predict the different behaviors of the bistable generator (these behaviors can coexist over certain frequency ranges) including the study of stability to small disturbances. This model highlights original behaviors for energy recovery: subharmonic behaviors whose frequency range allows increasing the overall generator bandwidth. In order to improve the accuracy of the model, a semi-analytical criterion is then added: the stability robustness criterion which characterizes the sensitivity of the different behaviors to external disturbances (the more robust a behavior, the easier to maintain over time). The model obtained and the experimental prototype show a wide frequency range on which the interesting behaviors (high orbits) and the undesirable behaviors (low orbits) coexist. The third part of this thesis therefore presents different strategies for jumping from low to high orbits by playing directly on the generator parameters. Finally, the fourth and last part focuses on the influence of the AC-DC interface circuit between the bistable generator and the load for future integration.

<p dir="ltr">Structural instability, traditionally deemed undesirable in engineering, can be leveraged for beneficial outcomes through intelligent design. One notable instance is elastic buckling, often leading to structures with two stable equilibria (bistable). Connecting bistable elements to form multistable mechanical metamaterials can enable the discretization and offer tunability of mechanical properties without the need for continuous energy input.<i> </i>In this work, we study the physics of these multistable metamaterials and utilize their state and property alterations along with snap-through instabilities resulting from state change for engineering applications. These materials hold potential for diverse applications, including mechanical and thermo-mechanical defrosting, energy absorption, energy harvesting, and mechanical storage and computation.</p><p dir="ltr">Focusing on defrosting, we find that the energy-efficient mechanical method using embedded bistable structures in heat exchanger fins significantly outperforms the thermal methods. The combination of manufacturing methods, material choice, boundary conditions, and actuation methodologies is systematically investigated to enhance defrosting performance. A purely mechanical strategy is effective against solid, glaze-like ice accumulations; however, performance is substantially diminished for low-density frost. To address this limitation, we study frost formation on the angular shape morphing fins and subsequently introduce a thermo-mechanical defrosting strategy. This hybrid approach focuses on the partial phase transition of low-density frost to solid ice through thermal methods, followed by mechanical defrosting. We experimentally validate this approach on a multistable heat exchanger fin pack.</p><p dir="ltr">Recent advancements have led to a new paradigm of reusable energy-absorbing materials, known as Phase Transforming Cellular Materials (PXCM) that utilize multiple negative stiffness elements connected in series. We explore the feasibility of this multistable metamaterial as frequency up-conversion material and utilize these phase transformations for energy harvesting. We experimentally demonstrate the energy-harvesting capabilities of a phase-transforming unit-cell-spring configuration and investigate the potential of multicell PXCM as an energy harvesting material.</p><p dir="ltr">The evolution towards intelligent matter, or physical intelligence, in the context of mechanical metamaterials can be characterized into four distinct stages: static, responsive, adaptive, and intelligent mechanical metamaterials. In the pursuit of designing intelligent mechanical metamaterials, there has been a resurgence in the field of mechanical computing. We utilize multistable metamaterials to develop mechanical storage systems that encode memory via bistable state changes and decode it through a global stiffness readout. We establish upper bounds for maximum memory capacity in elastic bit blocks and propose an optimal stiffness distribution for unique and identifiable global states. Through both parallel and series configurations, we realize various logic gates, thereby enabling in-memory computation. We further extend this framework by incorporating viscoelastic mechano-bits, which mimic the decay of neuronal action potentials. This allows for temporal stiffness modulation and results in increased memory storage via non-abelian behavior, for which we define a fundamental time limit of detectability. Additionally, we investigate information entropy in both elastic and viscoelastic systems, showing that temporal neural coding schemes can extend the system’s entropy beyond conventional limits. This is experimentally validated and shown to not only enhance memory storage but also augment computational capabilities.</p><p dir="ltr">The work in this thesis establishes multistability as a key design principle for developing responsive, adaptive, and intelligent materials, opening new avenues for future research in the field of multistable metamaterials.</p>

Le travail présenté dans ce mémoire constitue une ébauche des différentes études nécessaires au développement d'un microrobot d'exploration intratubulaire autonome inédit. Constitué d'un assemblage de cinq modules locomoteurs identiques, le futur microrobot devra inspecter des réseaux de tubes industriels de diamètre inférieur à 15 mm, présentant des coudes et des bifurcations. L'actionnement judicieux des différents modules permettra sa progression dans le tube, à la manière du lombric. Nos efforts se sont portés sur l'étude, la fabrication et la mise au point du module locomoteur, en cherchant à optimiser le paramètre 'vitesse de déplacement' du futur microrobot. Cet actionneur, de conception originale, est constitué d'un cadre forcé en postflambement, à deux états d'équilibre stable, dont le basculement d'un état à l'autre est commandé par des fils en Alliage à Mémoire de Forme (AMF). Une étude théorique à l'état d'équilibre, puis un modèle statique simplifié aux éléments finis, prenant en compte les grands déplacements de post-flambement lors du chargement menant au basculement, ont facilité le dimensionnement du cadre et le choix du matériau. Ensuite, des tests de caractérisation mécanique réalisés sur un prototype du module, à une échelle supérieure, ont été nécessaires pour l'adaptation de fils AMF éduqués. L'effet Joule étant le moyen de chauffage qui a été retenu pour engendrer la contraction de ces fils, nous évoquons quelques aspects liés à la commande d'un module, et au contrôle de la transformation des AMF par la mesure de leur résistance électrique. Enfin, une étude expérimentale du comportement au contact d'un module nous permet d'évaluer l'influence de différents paramètres sur les conditions de maintien du robot dans un tube vertical. Nous en déduisons alors les possibilités de charge embarquée par le futur microrobot, dans l'optique de le munir de capteurs et de sources d'énergie nécessaires à son autonomie.

Microvalves are essential components of the miniaturization of the fluidic systems to control of fluid flow in a variety of applications as diverse as chemical analysis systems, micro-fuel cells, and integrated fluidic channel arrangements for electronic cooling. Using microvalves, these systems offer important advantages: they can operate using small sample volumes and provide rapid response time. This PhD dissertation presents the world first electromagnetically actuated microvalve fabricated on a single wafer with CMOS compatibility. In this dissertation, the design, fabrication, and testing results of two different types of electromagnetic microvalves are presented: the on/off microvalve and the bistable microvalve with latching mechanism. The microvalves operate with power consumption of less than 1.5 W and can control the volume flow rate of DI water, or a 50% diluted methanol solution in the range 1 - 50 µL in. The leaking rate of the on/off microvalve is the order of 30 nL/min. The microvalve demonstrated a response time for latching of 10 ms in water and 0.2 ms in air. This work has resulted in a US patent, application no. 10/699,210.Other inventions that have been developed as a result of this research are bidirectional, and bistable-bidirectional microactuators with latching mechanism, that can be utilized for optical switch, RF relay, micro mirror, nano indenter, or nano printings.

Synaptic long-term modifications following neuronal activation are believed to be at the origin of learning and long-term memory. Recent experiments suggest that these long-term synaptic changes are all-or-none switch-like events between discrete states of a single synapse. The biochemical network involving calcium/calmodulin-dependent protein kinase II (CaMKII) and its regulating protein signaling cascade has been hypothesized to durably maintain the synaptic state in form of a bistable switch. Furthermore, it has been shown experimentally that CaMKII and associated proteins such as protein kinase A and calcineurin are necessary for the induction of long-lasting increases (long-term potentiation, LTP) and/or long-lasting decreases (long-term depression, LTD) of synaptic efficacy. However, the biochemical mechanisms by which experimental LTP/LTD protocols lead to corresponding transitions between the two states in realistic models of such networks are still unknown. We present a detailed biochemical model of the calcium/calmodulin-dependent autophosphorylation of CaMKII and the protein signaling cascade governing the dephosphorylation of CaMKII. As previously shown, two stable states of the CaMKII phosphorylation level exist at resting intracellular calcium concentrations. Repetitive high calcium levels switch the system from a weakly- to a highly phosphorylated state (LTP). We show that the reverse transition (LTD) can be mediated by elevated phosphatase activity at intermediate calcium levels. It is shown that the CaMKII kinase-phosphatase system can qualitatively reproduce plasticity results in response to spike-timing dependent plasticity (STDP) and presynaptic stimulation protocols. A reduced model based on the CaMKII system is used to elucidate which parameters control the synaptic plasticity outcomes in response to STDP protocols, and in particular how the plasticity results depend on the differential activation of phosphatase and kinase pathways and the level of noise in the calcium transients. Our results show that the protein network including CaMKII can account for (i) induction - through LTP/LTD-like transitions - and (ii) storage - due to its bistability - of synaptic changes. The model allows to link biochemical properties of the synapse with phenomenological 'learning rules' used by theoreticians in neural network studies.

No description available.

Les techniques de reconstruction de formes tridimensionnelles sont très largement utilisées dans de nombreux domaines, et notamment dans le domaine industriel ou médical. Et dans ces domaines, les techniques de mesure sans contact sont particulièrement étudiées, principalement parce qu'elles permettent de ne pas détériorer l'objet mesuré. Ce travail de thèse se place donc dans ce contexte et plus particulièrement dans le cas des dispositifs endoscopiques de mesure tridimensionnelle de surface par moyen optique. Dans le domaine médical, ce type d'instrument peut être appliqué à la coloscopie 3D ou à la chirurgie mini-invasive pour la détection de forme en surface de tissus biologiques. Dans cette thèse ce sont plus particulièrement les méthodes à base de stéréovision active ou passive, qui vont être étudiées et intégrées dans un dispositif miniaturisé. Différents modes de mesure vont être intégrés simultanément dans un unique instrument miniaturisé afin de permettre d'augmenter les performances de mesure : l'instrument peut adapter son principe de mesure à la texture de l'objet ou également à l'orientation des surfaces mesurées et plus généralement au contexte de la mesure. Ce travail de thèse est donc basé sur une étude algorithmique et instrumentale d'intégration de ces différents modes de mesure dans un unique instrument endoscopique miniaturisé. L'étude des modes de mesure par stéréovision a été réalisée en trois phases. Tout d'abord, c'est l'influence de l'orientation de la surface des objets mesurés dans un cas de stéréovision active qui est analysé. Puis une technique de basculement entre les voies de projection et d'acquisition du système de stéréovision active par actionnement bistable est proposé, ce qui permet d'adapter la mesure à l'orientation des surfaces à mesurer. Enfin, l'étude est orientée vers la possibilité de basculer d'un mode de stéréovision active vers un mode de stéréovision passive, toujours par actionnement bistable, le mode de stéréovision passive étant particulièrement adapté aux objets fortement texturés. Ainsi, trois modes de mesure sont réalisés dans ce nouveau système : deux modes de stéréovision active (avec inversion des voies de capture et de projection) et un mode de stéréovision passive. Pour réaliser la reconstruction tridimensionnelle, deux méthodes actives (par décalage de phase et par transformation de Fourier) et une méthode passive sont étudiées. Différentes performances de mesure sont obtenues selon les méthodes sélectionnées : un résultat de mesure plus précis est obtenu par les méthodes à. décalage de phase, une vitesse de mesure plus élevée est obtenu par les méthodes à transformée de Fourier ou par les méthodes passives. Le développement instrumental est également décrit dans cette thèse. Après modélisation optique et conception mécanique du système de mesure, un prototype de l'instrument endoscopique est fabriqué avec divers équipements spécifiques, tels qu'un DMD (Digital Micromirror Device), des guides d'images et des actionneurs électromagnétiques bistables. La validation expérimentale de la mesure tridimensionnelle est réalisée essentiellement sur objets mécaniques (du type mesure de détails sur pièce de monnaie), les deux méthodes actives et la méthode passives sont ainsi testées et confrontées. Enfin, une mesure sur un colon artificiel est réalisée par ce système pour se placer dans un contexte applicatif médical. / The techniques of three dimensional shapes reconstruction are widely used in many fields, particularly in the industrial or medical field. And in these areas, non-contact measurement techniques are particularly studied, mainly because they don't damage the measured object. This work therefore falls within this context and in particular in the case of endoscopic devices of surface coordinate measuring by optical methods. ln the medical field, this type of instrument can be applied to 3D colonoscopy or minimally invasive surgery to the surface in the form of biological tissues. In this thesis, methods based on active or passive stereo vision are the principle, which will be studied and integrated into a miniaturized device. Different measurement modes will be incorporated simultaneously into a single miniaturized instrument to help increase measurement performance: the instrument can adjust its measurement principle to the texture of the object or also to the orientation of measured surfaces more generally to the context of the measurement. This thesis is based on an algorithmic study and instrumental integration of these different measurement modes into a single miniaturized endoscopic instrument. The study of the measurement modes stereovision was conducted in three phases. First, it is the influence of the orientation of the measured objects' surface in a case of active stereovision being analyzed. And a technique of switching between the projection and acquisition in an active stereovision system by bistable actuation is proposed, which allows to adapt the measurement to the orientation of the measured surfaces. Finally, the study is oriented towards the ability to switch from one active stereovision mode to one passive stereovision mode, always by bistable actuator operation, the passive stereovision mode is particularly suitable for highly textured objects. Thus, three measurement modes are made in the new system: two modes of active stereovision (reversing capture and projection channels) and a mode of passive stereovision. To achieve three-dimensional reconstruction, two active methods (phase shift and Fourier Transform) and a passive method are studied. Different performance measurements are obtained according to methods selected: a more accurate measuring result is obtained by the phase shift methods; a high measurement speed is obtained by the Fourier transform methods or by passive methods. The instrumental development is also described in this thesis. After optical modeling and mechanical design of the measuring system, a prototype of the endoscopic instrument is manufactured with various specific devices such as a DMD (Digital Micromirror Deviee),images guides and bistable electromagnetic actuators. The experimental validation of the three-dimensional measurement is performed mainly on mechanical objects (such as details measurement on a coin), both active and passive method methods are well tested and compared. Finally, an artificial colon is measured by this system to be placed in a medical application context.