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La Sarcolipine, un régulateur de l’ATPase-Ca2+ SERCA1a : études in silico / Sarcolipin, a Regulator of Ca2+-ATPase SERCA1a : in Silico StudiesBarbot, Thomas 15 June 2018 (has links)
La Sarcolipine (SLN) est un hélice transmembranaire de 31 résidus dont la function est de reguler l’ATPase-Ca2+ SERCA1a. Ce régulateur peut subir une modification post-traductionnelle chez certaines espèces. Par exemple, chez le lapin, il est palmitoyle ou oleoylé sur le résidu Cys9. Pour comprendre au niveau moléculaire l’effet de cette modification post-traductionnelle sur la SLN, nous avons réalisé des simulations de dynamique moléculaire de la SLN de lapin insérée dans une bicouche de 1-palmitoyl-2-oléoyl-sn-glycéro-3-phosphocholine (POPC), non acylée et palmitoylée. L’analyse de ces simulations démontre que la palmitoylation n’affecte pas la structure secondaire, l’orientation (tilt et azimut), ainsi que l’enfouissemnt de la SLN dans la membrane. De plus, l’analyse de simulations tout atome de la SLN humaine insérée dans une bicouche de POPC montre que la SLN humaine a la même structure secondaire et orientation que la SLN de lapin mais est plus enfouie dans la membraneque celle de lapin, du fait de sa sequence en acides amines N-terminale plus hydrophobe.L’ATPase-Ca2+ SERCA1a, une ATPase de type P, est localisée dans la membrane du reticulum sarcoplasmique des cellules du muscle squelettique. Elle est impliquée dans les processus de contraction/relaxation musculaire en transportant rapidement le Ca2+ cytosolique dans le lumen du reticulum sarcoplasmique grâce à l’énergie fournie par l’hydrolyse de l’ATP. D’importants changements conformationnels de SERCA1a ont lieu durant son cycle catalytique comme le montrent les nombreuses structures cristallines de SERCA1a. En particulier, à l’état E1, la cavité contenant les sites de fixation du Ca2+ est ouverte vers le cytoplasme, tandis qu’à l’état E2, cette cavité est ouverte vers le lumen. La transition de l’état E1 à E2 nécessite la phosphorylation du résidu Asp351. Des structures 3D du complexe SERCA1a-SLN ont été déterminées par diffraction aux rayons X avec SERCA1a dans un état E1-Mg2+. Pour comprendre le mécanisme détaillé de la regulation de SERCA1a par la SLN, des simulations de dynamique moléculaire et des analyses des modes normaux (NMA) ont été réalisées en utilisant la structure 3D du complexe SERCA1a-SLN inséré dans une bicouche de POPC. Les résultats principaux de ces analyses sont les suivants : 1) la SLN régule les transitions E1.Mg2+ → E1.2Ca2+ et E1.Mg2+ → E2 ; 2) l’interaction de la SLN influe sur la structure et la dynamique de SERCA1a et modifie la position de l’hélice transmembranaire TM1 de sorte à ce que la cavité contenant les sites de fixation du Ca2+soit plus ouverte et que les sites soient plus accessibles ; 3) l’interaction de la SLN avec TM6 affecte deux regions de SERCA1a indispensables à sa fonction : en modifiant la structure et la dynamique de TM6, la SLN perturbe la position et la fluctuation des résidus des sites de fixation du Ca2+, leur conférant une conformation inapte à fixer le Ca2+. De même, l’interaction avec TM6 induit la courbure de TM5, ce qui affecte de façon indirecte le site de phosphorylation (éloigné de plus de 35 Å de la SLN) et conduit à l’inhibition de la phosphorylation du résidu Asp351.Nos résultats de cette étude in silico fournissent de nouveaux éléments concernant le mécanisme par lequel la SLN régule SERCA1a et qui pourrait être complétés par des travaux expérimentaux. / Sarcolipin (SLN), a transmembrane helix of 31 residues, binds to and regulates the Ca2+-ATPase SERCA1a. This regulator is post-translationnally modified in some species. For example, in rabbit, it is palmitoylated or oleoylated on its Cys9 residue. To understand at a molecular level, the effect of this post-translationnal modification on SLN, all-atom molecular dynamics simulations of unacylated and palmitoylated rabbit SLN embedded in a POPC bilayer were performed. Analysis of the simulations demonstrates that palmitoylation does not affect the secondary structure, the orientation (tilt and azimuth) as well as the burying of SLN within the membrane. In addition, the analyses of all-atom simulations of human SLN embedded in a POPC bilayer show that human SLN has the same secondary structure and orientation as rabbit SLN but is more buried within the membrane than rabbit SLN as a result of its more hydrophobic N-terminal amino acids sequence.The Ca2+ pump SERCA1a, a P-type ATPase, is localized in the sarcoplasmic reticulum membrane of striated muscle cells. It is involved in the contraction/relaxation process by fast pumping the cytoplasmic Ca2+ from the cytosol to the lumen of the sarcoplasmic reticulum using the energy of ATP hydrolysis. Large conformational changes of SERCA1a occur during its catalytic cycle as evidenced by the various crystal structures of SERCA1a. In particular, in the E1 state, the cavity that contains the Ca2+ binding sites is open toward the cytoplasm while in the E2 state, this cavity is open toward the lumen. The transition from the E1 to the E2 state involves the phosphorylation of Asp351 residue. 3D structures of SERCA1a-SLN complex have been determined by X-Ray diffraction, with SERCA1a in a E1-Mg2+ state. To understand the detailed mechanisms of SERCA1a regulation by SLN, molecular dynamics (MD) simulations and normal mode analysis (NMA) were performed using the 3D structures of SERCA1a-SLN complex embedded in a POPC bilayer. Main results from these analyses are the followings: 1) SLN regulates the E1-Mg2+ → E1-2Ca2+ and E1-Mg2+ → E2 state transitions; 2) interaction of SLN with SERCA1a impact the structure and dynamic of SERCA1a and modifies the position of the transmembrane helix TM1 such that the cavity that contains the Ca2+ binding sites is more widely opened and the Ca2+ binding sites more accessible; 3) SLN interaction with affects two regions essential to its function. By changing the structure and dynamic of TM6, SLN alters the position and fluctuations of residues involved in the Ca2+ binding sites, such that those sites are unable to bind Ca2+. This interaction with TM6 also induces TM5 bending and thus, indirectly modifies the phosphorylation site conformation, leading to the inhibition of Asp351 phosphorylation.Our results from these in silico studies provide new insights into the mechanism by which SLN regulates SERCA1a activity and could be completed by experimental work.
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Distortional Lateral Torsional Buckling of Doubly Symmetric Wide Flange BeamsArizou, Ramin 16 December 2020 (has links)
Distortional lateral-torsional buckling theories assume that the flanges remain undistorted, while the web is free to distort as a thin plate. Most theories adopt a cubic polynomial distribution along the web height to relate the lateral displacement of the web to the displacements and angles of twist both flanges. The present study develops a family of finite element solutions for the distortional buckling of wide flange beams in which the flanges are assumed to remain undistorted. In contrast to past theories, the lateral displacement distribution along the web height is characterized by superposing (a) two linear modes intended to capture the classical non-distortional lateral-torsional behavior and (b) any number of user-specified Fourier terms intended to capture additional web distortion. In the longitudinal direction, all displacement fields characterizing the lateral displacements are taken to follow a cubic distribution.
The first contribution of the thesis develops a finite element formulation that is able to replicate the classical non-distortional lateral torsional buckling solutions when the distortional modes are suppressed while enabling more accurate predictions for distortional lateral torsional buckling compared to those solutions based on the conventional cubic interpolation of the lateral displacement. The formulation is used to conduct an extensive parametric study to quantify the reduction in critical moments due to web distortion relative to the classical non-distortional predictions in the case of simply-supported beams, cantilevers, and beams with an overhang. The solution is then used to generate interaction curves for beams with an overhang subjected to various proportions of uniformly distributed and point loads.
The second contribution of the thesis adds two additional features to the formulation (a) to capture the destabilizing effect due to the load height relative to the shear center and (b) a module that incorporates any number of user-defined multi-point kinematic constraints. The additional features are employed to investigate the effect of load height, bracing height, and combined effects thereof in practical design problems. A distortional indicator is then introduced to characterize the distribution of web distortion along the beam span as the beam undergoes distortional lateral buckling. A systematic design optimization technique is then devised to identify the location(s) along the span at which the addition of transverse stiffeners would maximize the critical moment capacity.
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Matrices de bolomètres supraconducteurs pour la mesure de la polarisation du fond diffus cosmologique : application à l’expérience QUBIC / TES-arrays for the detection of CMB B-mode polarisation : application to the QUBIC experimentPerbost, Camille 16 December 2016 (has links)
Le fond diffus cosmologique (CMB) est la première lumière libérée par l’Univers.À ce titre, elle constitue la photographie la plus ancienne à laquelle nous ayons accès.Ces photons recèlent des trésors d’informations capables de nous renseigner tant sur le contenu énergétique de l’Univers que sur son histoire. En retraçant son évolution jusqu’aujourd’hui, on est capable d’établir des scénarios quant à la période qui a précédé l’émission du CMB, inaccessible aux observations. Plus particulièrement,la plupart des modèles s’accordent à dire que l’Univers aurait connu juste après le Big Bang une période d’expansion exponentielle qualifiée d’inflation. L’un des défis majeurs de la cosmologie consiste à confirmer et contraindre ces modèles en cherchant sur le CMB les empreintes théoriques laissées par l’inflation : un motif de polarisation qualifié de mode B. Cependant, ce signal est attendu à un niveau très faible, sa détection requiert donc la mise en place d’instruments extrêmement sensibles. Cette thèse s’inscrit dans l’effort technologique mené au sein du projet QUBIC pour cette quête. Dans cette optique on s’est intéressé aux détecteurs, des matrices de plusieurs centaines de bolomètres supraconducteurs. Dans un premier temps, on a défini une méthode permettant de dimensionner les détecteurs et la matrice pour répondre au mieux à nos attentes à travers l’ajustement de paramètres pertinents. Puis on a mené pour la première fois dans la collaboration toute la réalisation d’une matrice de 256détecteurs sur laquelle on a par la suite effectué et exposé des tests préliminaires prometteurs pour la future implémentation du plan focal de QUBIC. / The cosmic microwave background (CMB) is the very first light of the Uni- verse and thus constitutes the oldest picture of its initial state. These photons carry valuable information constraining both the energy content and the history of the Universe. CMB observations allow us to reconstruct what occurred before the CMB anisotropies were imprinted. The most promising theoretical models all postulate an epoch of exponential expansion known as inflation just after the Big Bang. One of the major challenges of observational cosmology is hence to confirm or falsify inflation as well as to discover how inflation was realized in a particular model by searching for its imprint on the CMB polarization B-mode. This signal is however expected to be extremely weak and its detection requires a very sensitive experiment. This thesis reports on contributions to the technology development for the innovative QUBIC instrument, focusing on the perfection of an array of several hundreds of supercon- ducting bolometric detectors. A method was defined to design the detector array through tuning the relevant parameters to best meet our requirements. Then a 256- detector prototype array was fully manufactured and characterized. The preliminary characterization gave promising results for the forthcoming implementation of the QUBIC focal plane.
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Development of the B-mode measurements pipeline for QUBIC experiment / D´eveloppement du pipeline de mesure des modes B pour l’expérience QUBICStolpovskiy, Mikhail 25 November 2016 (has links)
QUBIC est une expérience au sol en cours de construction dont le but est de mesurer les modes-B primordiaux du fond diffus cosmologique en utilisant la technique innovante de l’interférométrie bolométrique. Grace à la fusion entre interférométrie et imagerie,QUBIC a une très bonne sensibilité et un excellent contrôle des effets systématiques instrumentaux. De plus, du fait de la dépendance en fréquence du lobe synthétique,QUBIC peut être utilisé comme un spectre-imageur. Ces points pris en compte, la sensibilité globale de QUBIC au rapport tenseur/scalaire est 0.012. L’objectif de cette thèse est de d´écrire le code d’analyse de données de QUBIC, depuis la fabrication de cartes`a partir des données temporelle jusqu’`a la séparation de composantes astrophysique, l’estimation du spectre de puissance angulaire et celle des paramètres cosmologiques.Les aspects essentiels de ce travail sont les suivants: la fabrication de carte qui est très inhabituelle vis à vis des autres projets du domaine et le développement de la stratégie de couverture du ciel pour QUBIC. / QUBIC is a ground-based experiment aiming to measure the primordial B-modes, currently under construction, that uses the novel bolometric interferometry technique. Thanks to the fusion nature of QUBIC, it has very good sensitivity and excellent control of systematics. Moreover, the fact that the synthesized beam depends on the wavelength allows us to treat QUBIC as a spectro-polarimeter. These factors together give sensitivity on tensor-to-scalar ratio r 0.012. The goal of this thesis is to describe the pipeline of data analysis for QUBIC, from map-making of CMB from raw time-ordered data, through component separation and power spectra estimation to cosmological parameter estimation. The main accents of this work are: map-making, which is very unusual in comparison with other experiments in the field, and the development of scanning strategy for QUBIC.
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Investigating Energy Consumption and Responsiveness of low power modes in MicroPython for STM32WB55Samefors, Albin, Sundman, Felix January 2023 (has links)
Introduction: This paper presented an analysis of the energy consumption and responsiveness of MicroPython in an embedded system. The purpose of this study was to understand the energy consumption and response time of a MicroPython based system to optimize its overall performance and efficiency. Two research questions had been formulated to concretize the purpose of this thesis: [RQ1] How does the energy consumption of a MicroPython based embedded system compare to that of a C-based embedded system for tasks utilizing low power modes? [RQ2] What is the wake-up response time of MicroPython for low power modes when receiving external and internal interrupts, and how does it compare to an established language like C on an embedded system? Method: To answer the research questions and achieve the purpose, an experimental study was conducted. The energy consumption of the MicroPython based system was analyzed under different scenarios. The time it took for MicroPython to respond to an interrupt request from a sleeping state was also measured. The data collected from the experiment was analyzed to determine the level of energy consumption and responsiveness of MicroPython in an embedded system. Results: The results indicated that C was generally more energy efficient and responsive than MicroPython for tasks utilizing low power modes for the Deepsleep mode. Although MicroPython proved to have shorter response times for the Lightsleep low power mode. For energy consumption, C was more stable in the measurements while MicroPython reached both lower minimum currents and higher maximum currents. Conclusions: In conclusion, this study found that while MicroPython could achieve lower power levels than C in both low power modes tested, it reached higher current levels upon waking up. Despite this, MicroPython could still be a choice for applications that spend longer durations in low power modes, as this could offset the increased current spikes during wake-up. Response times for MicroPython were faster than C in the Lightsleep internal interrupt case, but MicroPython exhibited significantly longer response times in the Deepsleep mode due to the system resetting and restarting the interpreter. Keywords: Embedded systems, Energy consumption, Interrupt requests, Low power modes, MicroPython, Responsiveness.
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The Aerodynamic Excitation of Trapped Diametral Acoustic Modes in Rectangular Ducted CavitiesBolduc, Michael 11 1900 (has links)
The excitation mechanism of trapped diametral acoustic modes within a rectangular cavity-duct system is investigated both numerically and experimentally. The asymmetry inherent within the rectangular geometry introduces a preferred orientation, ensuring the excited diametral modes remain stationary. Three separate cavities are manufactured and tested. This included two asymmetric rectangular cross-sections and one symmetric square cavity. Experimental results indicate that the aeroacoustic responses of the three cavities are dominated by the strong excitation of trapped diametral modes. Numerical simulations indicate that the resolved radial acoustic particle velocity distributions are non-uniform at the upstream separation edge where the formation of vortical structures is initiated. As the cavity became smaller, and more asymmetric, the trapped nature of the acoustic modes decreased with an accompanied increase in the radiation losses and reduction in pulsation amplitude. Observations of the aeroacoustic measurements show evidence of three unique modal behaviours. The first case is the independent excitation of a single stationary mode where specific circumferential sections of the shear layer were excited and initiating the formation of vortical disturbances. These circumferential sections, and distribution of disturbances, were akin to the excited mode shape. The second case involved simultaneous excitation of two stationary modes. This suggested that the shear layer was exciting two modes simultaneously. Neighbouring circumferential sections, at the initial region of the shear layer, were being excited independently and at different resonant frequencies. Finally, a spinning trapped acoustic mode was observed in the symmetric square cavity. Due to the spinning nature, the excited circumferential portions and formation of vortices were non-uniform and rotated with the spinning acoustic mode. This resulted in the formation of a three-dimensional helical structure. / Thesis / Master of Applied Science (MASc)
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A Dispersion Formula for Analyzing Modal Interference Among Guided and Free Electromagnetic Wave Modes and Other Phenomena in a Circular Optical FiberKarunanayaka, Prasanna Rasika January 2004 (has links)
No description available.
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Réduction de modèle et contrôle en boucle fermée d'écoulements de type oscillateur et amplificateur de bruitBarbagallo, Alexandre 14 January 2011 (has links) (PDF)
Ce travail est consacré au contrôle en boucle fermée des perturbations se développant linéairement dans des écoulements laminaires et incompressibles de types oscillateurs et amplificateurs de bruit. La loi de contrôle, calculée selon la théorie du contrôle LQG, est basée sur un modèle d'ordre réduit de l'écoulement obtenu par projection de Petrov-Galerkin. La stabilisation d'un écoulement de cavité de type oscillateur est traitée dans une première partie. Il est montré que la totalité de la partie instable de l'écoulement (les modes globaux instables) ainsi que la relation entrée-sortie (action de l'actionneur sur le capteur) de la partie stable doivent être captées par le modèle réduit afin de stabiliser le système. Les modes globaux, modes POD et modes BPOD sont successivement évalués comme bases de projection pour modéliser la partie stable. Les modes globaux ne parviennent pas à reproduire le comportement entrée-sortie de la partie stable et par conséquent ne peuvent stabiliser l'écoulement que lorsque l'instabilité du système est initialement faible (nombre de Reynolds proche de la criticité). En revanche, les modes POD et plus particulièrement BPOD sont capable d'extraire la dynamique entrée-sortie stable et permettent de stabiliser efficacement l'écoulement. La seconde partie de ce travail est consacrée à la réduction de l'amplification des perturbations sur une marche descendante. L'influence de la localisation du capteur et de la fonctionnelle de coût sur la performance du compensateur est étudiée. Il est montré que la troncature du modèle réduit peut rendre le système bouclé instable. Finalement, la possibilité de contrôler une simulation non-linéaire avec un modèle linéaire est évaluée.
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Experimental studies of tearing mode and resistive wall mode dynamics in the reversed field pinch configurationMalmberg, Jenny-Ann January 2003 (has links)
It is relatively straightforward to establish equilibrium inmagnetically confined plasmas, but the plasma is frequentlysucceptible to a variety of instabilities that are driven bythe free energy in the magnetic field or in the pressuregradient. These unstable modes exhibit effects that affect theparticle, momentum and heat confinement properties of theconfiguration. Studies of the dynamics of several of the mostimportant modes are the subject of this thesis. The studies arecarried out on plasmas in the reversed field pinch (RFP)configuration. One phenomenon commonly observed in RFPs is mode walllocking. The localized nature of these phase- and wall lockedstructures results in localized power loads on the wall whichare detrimental for confinement. A detailed study of the walllocked mode phenomenon is performed based on magneticmeasurements from three RFP devices. The two possiblemechanisms for wall locking are investigated. Locking as aresult of tearing modes interacting with a static field errorand locking due to the presence of a non-ideal boundary. Thecharacteristics of the wall locked mode are qualitativelysimilar in a device with a conducting shell system (TPE-RX)compared to a device with a resistive shell (Extrap T2). Atheoretical model is used for evaluating the threshold valuesfor wall locking due to eddy currents in the vacuum vessel inthese devices. A good correlation with experiment is observedfor the conducting shell device. The possibility of succesfully sustaining discharges in aresistive shell RFP is introduced in the recently rebuiltdevice Extrap T2R. Fast spontaneous mode rotation is observed,resulting in low magnetic fluctuations, low loop voltage andimproved confinement. Wall locking is rarely observed. The lowtearingmode amplitudes allow for the theoretically predictedinternal nonresonant on-axis resistive wall modes to beobserved. These modes have not previously been distinguisheddue to the formation of wall locked modes. The internal andexternal nonresonant resistive wall modes grow on the timescale of the shell penetration time. These growth rates dependon the RFP equilibrium. The internal nonresonant resistive wallmodes dominate in Extrap T2R, especially for shallow reverseddischarges. The external nonresonant modes grow solely in deepreversal discharges. <b>Keywords</b>Nuclear fusion, reversed field pinch, resistiveinstabilities, wall locked modes, tearing modes, resistiveshell modes, field errors, EXTRAP-T2, EXTRAP-T2R, TPE-RX
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Experimental studies of tearing mode and resistive wall mode dynamics in the reversed field pinch configurationMalmberg, Jenny-Ann January 2003 (has links)
<p>It is relatively straightforward to establish equilibrium inmagnetically confined plasmas, but the plasma is frequentlysucceptible to a variety of instabilities that are driven bythe free energy in the magnetic field or in the pressuregradient. These unstable modes exhibit effects that affect theparticle, momentum and heat confinement properties of theconfiguration. Studies of the dynamics of several of the mostimportant modes are the subject of this thesis. The studies arecarried out on plasmas in the reversed field pinch (RFP)configuration.</p><p>One phenomenon commonly observed in RFPs is mode walllocking. The localized nature of these phase- and wall lockedstructures results in localized power loads on the wall whichare detrimental for confinement. A detailed study of the walllocked mode phenomenon is performed based on magneticmeasurements from three RFP devices. The two possiblemechanisms for wall locking are investigated. Locking as aresult of tearing modes interacting with a static field errorand locking due to the presence of a non-ideal boundary. Thecharacteristics of the wall locked mode are qualitativelysimilar in a device with a conducting shell system (TPE-RX)compared to a device with a resistive shell (Extrap T2). Atheoretical model is used for evaluating the threshold valuesfor wall locking due to eddy currents in the vacuum vessel inthese devices. A good correlation with experiment is observedfor the conducting shell device.</p><p>The possibility of succesfully sustaining discharges in aresistive shell RFP is introduced in the recently rebuiltdevice Extrap T2R. Fast spontaneous mode rotation is observed,resulting in low magnetic fluctuations, low loop voltage andimproved confinement. Wall locking is rarely observed. The lowtearingmode amplitudes allow for the theoretically predictedinternal nonresonant on-axis resistive wall modes to beobserved. These modes have not previously been distinguisheddue to the formation of wall locked modes. The internal andexternal nonresonant resistive wall modes grow on the timescale of the shell penetration time. These growth rates dependon the RFP equilibrium. The internal nonresonant resistive wallmodes dominate in Extrap T2R, especially for shallow reverseddischarges. The external nonresonant modes grow solely in deepreversal discharges.</p><p><b>Keywords</b>Nuclear fusion, reversed field pinch, resistiveinstabilities, wall locked modes, tearing modes, resistiveshell modes, field errors, EXTRAP-T2, EXTRAP-T2R, TPE-RX</p>
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