There has been an increasing interest in the field of `smart structures' and `smart materials'. In constructing smart structures, a class of materials called smart materials are often used as sensors and actuators. An example of a smart material is shape memory alloy (SMA). A common actuator configuration uses an SMA wire with a constant load. The non-linear input-output behaviour of SMAs, known as hysteresis, made them difficult to model and control. The research in this thesis examines the effect of PID-controller gain optimization on SMA wire control at different frequencies of operation. A constant-load SMA wire actuator with a PID-controller is used in the study. Heat is applied to the wire using an input electric current. The system is cooled through convection with the surrounding area. The lack of active cooling prevents the system from operating at high frequencies. Three different cost functions are proposed for various applications. The Preisach model is chosen to model the hysteretic behaviour of the SMA wire contraction. Varying material properties such as electrical resistance and heat capacities are modelled to give a more accurate representation of the system's physical behaviour. Simulations show that by optimizing the controller gain values, the bandwidth of the system is improved. An interesting observation is made in the heating cycle of the SMA wire. In order to achieve faster cooling, overshoot is observed at low frequencies. This is a result of the system hysteresis. The system hysteresis allows different input signals to achieve the same output value. Since the rate of cooling is proportional to the temperature above ambient, better cooling is achieved by reaching a higher temperature. The error caused by the overshoot is compensated by the better cooling phase, which is not actively controlled.

Les amyotrophies spinales proximales sont des maladies génétiques neuromusculaires caractérisées par la dégénérescence des motoneurones spinaux et une atrophie des muscles squelettiques proximaux. La perte de fonction du gène smn1, un gène essentiel à la survie des motoneurones, entraîne une réduction drastique du niveau de protéine SMN et est, à l’origine des symptômes observés chez les patients. L'amphibien anoure Xenopus tropicalis constitue un très bon petit animal modèle pour étudier cette maladie ainsi que le développement des motoneurones. En effet une diminution de la production de la protéine SMN via l’utilisation de morpholinos a permis de montrer chez les têtards, des défauts de migration des motoneurones ainsi qu’une atrophie des muscles caudaux. Pour développer un modèle héritable de SMA, nous avons utilisé des nucléases tels que les ZFN ou le système CRISPR/Cas pour générer des mutations du gène smn chez Xenopus tropicalis. Nous avons conçu les outils moléculaires pour induire différentes mutations du gène smn avec des ZFN ou le système CRISP/Cas9. Nous avons ensuite validé l'efficacité de ces nucléases dans des embryons in vivo et développé une méthode de recherche de mutations basée sur l’utilisation des endonucléases T7EI et Surveyor. Nous avons obtenu un animal fondateur mutant qui permettra de générer des embryons homozygotes pour la mutation. En parallèle, nous avons développé une lignée transgénique chez Xenopus tropicalis permettant de visualiser les populations de motoneurones spinaux, pour mieux caractériser les animaux mutants smn in vivo. La combinaison de ces deux lignées permettra de mieux comprendre la physiopathologie motoneuronal liée à des mutations de smn. / Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by motor neuron loss and skeletal muscle atrophy. In human the loss of function of the smn1 gene, the main supplier of survival motor neuron protein (SMN), leads to reduced levels of SMN and eventually to SMA. The anuran amphibian Xenopus tropicalis is a good animal model for the study of SMA and motor neurons development. Indeed the inhibition of the production of SMN using antisense morpholinos leads to caudal muscular atrophy in tadpoles. To develop an inheritable SMA model, we edited the smn gene in X. tropicalis using zinc-finger nucleases (ZFNs) and CRISPR/Cas system. As a first step, we designed the molecular tools needed to induce mutations of the smn gene using ZFN and CRISPR/cas9. Next we probed the efficiency of these tools and developed a method to identify mutations using T7EI and Surveyor endonucleases. We obtained a mutant frog and thus we will be able to produce homozygous mutant embryos for smn. In parallel we developed a transgenic line of Xenopus tropicalis frogs in which we can image motor neurons populations in vivo. The combination of both lines should enable to increase our knowledge and understanding of motor neuron physiopathology due to smn mutations.

No description available.

Spinal Muscular Atrophy (SMA) is an autosomal recessive motor neuron disease. SMA is associated with homozygous mutations in the Survival of Motor Neuron gene I (SMN1). SMN protein does not appear to exist in cells in isolation but associates with several proteins to form a large multi-protein complex. The functions of SMN complex include assembly, metabolism and transport of diverse classes of ribonucleoproteins. X- Linked Spinal Muscular Atrophy is a rare congenital disorder characterized by multiple joint contractures. It is associated with hypotonia, areflexia, chest deformities and congenital joint contractures. A candidate interval was defined for XL-SMA in Xp11.3-Xq11.2 in 1995. The purpose of this study was to refine the XL-SMA gene region and discover the XL-SMA gene. In addition to that, the gene product was investigated to delineate the genotype-phenotype correlation. My studies were focused on single nucleotide polymorphism (SNP) analysis. The candidate gene interval was refined by studying 14 SNPs in the three largest families. This analysis revealed a recombination event which allowed elimination of the NDP gene. Significantly positive LOD scores were obtained from these SNP studies. The exons and exon-intron boundaries of 12 genes were screened. No mutations were found in these genes in affected male samples. In late 2006, UBE1 (Ubiquitin activating enzyme 1) was discovered as the XL-SMA gene. UBE1 protein is responsible for the first step of ubiquitination of proteins in a cell. To investigate a possible common molecular mechanism between SMA and XL-SMA, proteins in the SMN Complex in XL-SMA patient cell lines were studied. SMN and Gemin3 protein levels were found to be consistently lower in XL-SMA patient cell lines (lymphoblasts) compared to healthy cell line. These results imply that there may be a common disease mechanism. To understand if the SMN and Gemin3 RNA levels decrease. RNA expression studies were performed. These studies confirmed that there is no difference of RNA expression of SMN and Gemin3 in XL-SMA cell lines when compared to healthy cell lines. As for UBE1, the same experimental procedure for SMN Complex proteins were repeated with antibodies to UBE1 to determine if there is any decline of UBE1 protein levels in XL-SMA patient cell lines compared to a healthy cell line. There was a decline in protein levels of UBE1 in XL-SMA patients. Two possible models are proposed for a molecular mechanism in XL-SMA: 1) UBE1 involves in degradation of a protein which downregulates SMN Complex (or a protein which stabilizes SMN Complex). When UBE1 is mutated, the protein in question is not degraded and this results in excess downregulation of SMN Complex (maybe via a pathway involving SMN-Gemin3 interaction). 2) UBE1 and UBA6 interact with the proteins of SMN Complex as they monoubiquinate them for different cellular processes. When UBE1 is mutated, UBA6 cannot compensate the deficiency of UBE1, which in turn disrupts normal cellular RNA metabolism required for motor neuron development and survival.

El Stone Mastic Asphalt, SMA, diseño de origen alemán desarrollado en los años 60 ha permitido dar solución a los problemas de tránsitos pesados y climas fríos, de las carreteras en Europa, EE.UU. y Canadá y recientemente en Brasil y Argentina. El concepto de diseño SMA se basa en una estructura granular donde predomina el contacto piedra-piedra el mismo que le provee de alta resistencia cortante, baja deformación permanente o “rutting” y considera un buen porcentaje de ligante que le confiere una excelente durabilidad.

No description available.

Membrane proteins are involved in several fundamental biological processes such as transport or signal transduction. Most of them are enzymes, receptors or other important biological macromolecules representing up to 70% of therapeutic targets. Despite the interest in understanding their structures and behaviour the scientific knowledge is still very limited due to several practical difficulties. In 2009 a new platform for membrane protein studies called SMALP (Styrene-Maleic Acid Lipid Particles) nanodiscs was introduced. SMALPs are self-assembled structures formed by a bilayer of phospholipids controlled in diameter by a polystyrene maleic acid (SMA) copolymer belt. The purpose of this research project herein presented was to structurally characterise SMALPs, with analyses aimed to understand the role of both the polymeric and lipid parts in the self-assembly process. A series of investigations were carried out to elucidate the specific copolymer characteristics that allow the assembly into such well-defined, stable and reproducible structures. Experiments performed via small angle X-ray (SAXS) and neutron (SANS) scattering together with nuclear magnetic resonance (NMR), gel-filtration chromatography (GPC), dynamic light scattering (DLS), allowed identification of the specific polymeric characteristics of the copolymer architecture which were revealed to be crucial for the SMALPs assembly process. Investigations performed also addressed the question whether it was possible to assemble nanodiscs with the use of different phospholipids (with different chain length and charged or non-charged heads) and what the impact of the different lipids had on the structures. Finally, further analyses were made to test the physical chemical behaviour of the SMALPs when important environmental parameters such as temperature, pH and salt concentration of the buffer were changed.

There has been an increasing interest in the field of `smart structures' and `smart materials'. In constructing smart structures, a class of materials called smart materials are often used as sensors and actuators. An example of a smart material is shape memory alloy (SMA). A common actuator configuration uses an SMA wire with a constant load. The non-linear input-output behaviour of SMAs, known as hysteresis, made them difficult to model and control. The research in this thesis examines the effect of PID-controller gain optimization on SMA wire control at different frequencies of operation. A constant-load SMA wire actuator with a PID-controller is used in the study. Heat is applied to the wire using an input electric current. The system is cooled through convection with the surrounding area. The lack of active cooling prevents the system from operating at high frequencies. Three different cost functions are proposed for various applications. The Preisach model is chosen to model the hysteretic behaviour of the SMA wire contraction. Varying material properties such as electrical resistance and heat capacities are modelled to give a more accurate representation of the system's physical behaviour. Simulations show that by optimizing the controller gain values, the bandwidth of the system is improved. An interesting observation is made in the heating cycle of the SMA wire. In order to achieve faster cooling, overshoot is observed at low frequencies. This is a result of the system hysteresis. The system hysteresis allows different input signals to achieve the same output value. Since the rate of cooling is proportional to the temperature above ambient, better cooling is achieved by reaching a higher temperature. The error caused by the overshoot is compensated by the better cooling phase, which is not actively controlled.

No description available.

L’amyotrophie spinale infantile (SMA) est une maladie neurodégénérative rare, caractérisée par une perte progressive des motoneurones de la moelle épinière, et pour laquelle aucun traitement curatif n’est disponible. Cette maladie est causée par la mutation du gène SMN1 qui induit une diminution de l’expression de la protéine SMN. Depuis plusieurs des années, notre l’équipe examine les effets de l’exercice sur le développement ou le maintien de l’unité motrice dans des maladies neurodégénératives affectant spécifiquement le motoneurone. Ces études ont notamment permis de mettre en évidence que l’exercice physique pourrait avoir des effets bénéfiques pour l’amyotrophie spinale, dans un modèle de souris SMA de type 2 soumis à un exercice de course sur roue pendant 5 jours (Grondard et al., 2005). Dans notre étude, nous avons comparé les effets de deux programmes d’entraînement différents, d’une durée de 10 mois, basés sur un exercice de course ou sur un exercice de nage, sur des populations de souris SMA de type 3, la forme la moins sévère de la maladie. Dans nos conditions, la course est un exercice de faible intensité et de faible amplitude, mais qui induit plus de lésions musculaires, au contraire de la nage, comme le confirme les mesures de lactate et de créatine kinase circulants. Ces deux paramètres ont des valeurs anormalement hautes chez les souris SMA, suggérant des anomalies métaboliques et de fragilité musculaire, qui sont limitées par les deux programmes d’entraînement. Les analyses du comportement moteur indiquent également que les 10 mois d’entraînement améliorent significativement les capacités motrices des souris SMA, et notamment la résistance à la fatigue avec la nage. Comme attendu, la perte de 46% des motoneurones spinaux enregistrée à 12 mois chez les souris SMA sédentaires est significativement limitée par les deux types d’entrainement, mais avec des efficacités différentes sur les différentes sous‐populations de motoneurones spinaux. En effet, la course protège préférentiellement les motoneurones de faible surface et exprimant ERR‐β, assimilés à des motoneurones lents, et la nage les motoneurones de large surface et exprimant Chodl, assimilés à des motoneurones rapides. De manière surprenante, la neuroprotection induite par l’exercice est indépendante de l’expression de SMN dans la moelle épinière des souris SMA. Une étude de la forme et de la surface des jonctions neuromusculaires dans trois muscles du mollet, le soleus, le plantaris et le tibialis, et une étude du phénotype musculaire de ces mêmes trois muscles confirment le rôle bénéfique de l’entrainement mais aussi les effets différentiels des deux programmes, avec un effet plus important pour la nage. Les améliorations de l’unité motrice, induites par l’exercice, permettent un meilleur fonctionnement neuromusculaire, comme le suggère les mesures électrophysiologiques du muscle plantaire. Pris tous ensemble, ces résultats suggèrent qu’un exercice de nage, à haute intensité, dans des conditions anaérobies, et axé sur le recrutement des muscles extenseurs pourrait être bénéfique pour les patients SMA, notamment pour améliorer les capacités motrices et donc la qualité de vie des patients. / Objective: Spinal Muscular Atrophy (SMA) is a group of autosomal recessive neurodegenerative diseases differing in their clinical outcome, characterized by the specific loss of spinal motor‐neurons, caused by insufficient levels of SMN protein expression. No cure is presently available for SMA. While physical exercise might represent a promising approach for alleviating SMA symptoms, the lack of data dealing with the effects of different exercise types on diseased motor‐units still precludes the use of exercise in SMA patients. Methods: We have evaluated the efficiency of two long‐term physical exercise paradigms, either based on high intensity swimming or on low intensity running, in alleviating SMA symptoms in a mild type 3 SMA‐like mouse model. Results: We found that a 10‐month physical training induced significant benefits in terms of resistance to muscle damages, energetic metabolism, muscle fatigue and motor behavior. Both exercise types significantly enhanced motor‐neuron survival, independently of SMN expression, leading to the maintenance of neuromuscular junctions and skeletal muscle phenotypes, particularly in the soleus, plantaris and tibialis of trained mice. Most importantly, both exercises significantly improved neuromuscular excitability properties. Besides, all these training‐induced benefits are quantitatively and qualitatively related to the specific characteristics of each exercise, suggesting that the related neuroprotection is strongly dependent on the specific activation of some motor‐neuron subpopulations. Interpretation: Taken together, the present data show significant long‐term exercise benefits in a mild type 3 SMA context and provide important clues for designing rehabilitation programs in patients.