Islet amyloid polypeptide (IAPP) is a 37-residue amyloidogenic hormone implicated in the progression of Type II Diabetes (T2D). T2D affects an estimated 422 million people yearly and is a co-morbidity with numerous diseases. IAPP forms toxic oligomers and amyloid fibrils that reduce pancreatic β-cell mass and exacerbate the T2D disease state. Toxic oligomer formation is attributed, in part, to the formation of inter-peptide β-strands comprised of residues 23-27 (FGAIL). Flavonoids, a class of polyphenolic natural products, have been found experimentally to inhibit IAPP aggregate formation. Many of these known IAPP aggregation attenuating small flavonoids differ structurally only slightly; the influence of functional group placement on inhibiting the aggregation of the IAPP(20-29) has yet to be explored. To probe the role of small-molecule structural features that impede IAPP aggregation, molecular dynamics (MD) simulations were performed on a model fragment of IAPP(20-29) in the presence of morin, quercetin, dihydroquercetin, epicatechin, and myricetin. Contacts between Phe23 residues are critical to oligomer formation, and small-molecule contacts with Phe23 are a key predictor of β-strand reduction. Structural properties influencing the ability of compounds to disrupt Phe23-Phe23 contacts include carbonyl and hydroxyl group placement. These structural features influence aromaticity and hydrophobicity, principally affecting ability to disrupt IAPP(20-29) oligomer formation. This work provides key information on design considerations for T2D therapeutics. / Master of Science in Life Sciences / Type II Diabetes (T2D) affects an estimated 422 million people worldwide, with the World Health Organization (WHO) reporting that approximately 1.5 million deaths were directly caused by T2D in 2019. The progression of T2D has been attributed to a protein, called islet amyloid polypeptide (IAPP, or amylin) that is co-secreted with insulin after individuals eat or consumes calories. IAPP has been discovered to form toxic aggregates or clumps of protein material that worsen the disease state and cause a loss of mass of pancreatic cells. There is a large market for therapeutics of T2D and more small molecule drugs are needed to slow progression and severity of T2D. Flavonoids, a class of natural molecules, have been found to inhibit the processes by which IAPP promotes T2D disease progression by stopping the aggregation of IAPP. The structures of these flavonoid compounds differ slightly but show difference in ability to slow IAPP aggregation. By understanding how those differences confer more or less protection against T2D and inhibit IAPP aggregation, we can design more potent and specific drugs to target IAPP. To probe the role of molecular structure in preventing IAPP aggregation, molecular dynamics (MD) simulations — a powerful computational technique — were performed on a model fragment of IAPP in the presence of molecules morin, quercetin, dihydroquercetin, epicatechin, and myricetin. MD simulations provide extremely detailed information about potential drug interactions with a given target, serving as an important tool in the development of new drugs. This work has identified key features and predictors of effective IAPP drugs, providing a framework for the further development of therapeutics against T2D and similar diseases.

Prior to launch, space craft instruments need to be tested in a relevant environment to prove operational functionality. Thus, we have developed an ion source to stimulate thermal plasma instruments in a vacuum chamber. This dissertation presents the mechanical design of the source, simulations of the potentials and charged particle trajectories in and around the source, and vacuum chamber measurements of the emitted ion beam. Once the ion source is understood, it is successfully used to test a typical ion instrument. Further aspects of the ion source, efficiency, thermionic filament emission, and collision frequencies are also discussed. / Doctor of Philosophy / Satellites have become a critical resource for business and governments. The study of the high edge of the earth’s atmosphere, where satellites operate, is difficult because the physics of this region is so complex. More measurements of the upper atmosphere are needed to understand exactly how it works and improve the computer models simulating the atmosphere. The instruments used to measure this region need to be validated before they are launched. This dissertation describes the design and testing of an ion source device that can produce charged particles in a very low pressure environment, such as a vacuum chamber, to create conditions similar to those an instrument would encounter in orbit. Computer simulations and physical tests of the source are presented, compared, and found to match. Finally, an actual satellite instrument is successfully validated with the source.

<p dir="ltr">Plant and algae-based biofuels offer a compelling green energy solution, but the utility of biological photosynthesis is limited by inefficiency in energy production. Without the connection between the protein structure and optical spectra, it is challenging to modify optical properties for improving energy production. Chlorophyll proteins (CPs) are the primary work-horses of biological photosynthesis that absorb and transfer solar energy to chemically active reaction centers and control the chemical energy storage process. While the CP structures are well-known, predicting their optical and electronic properties remains a serious challenge. There are computational complications for treating large, electronically coupled molecular pigments embedded in a dynamically structured protein environment. In this work, we aim to address some prominent issues with structure-based optical spectra predictions and the limitations in applying the Frenkel exciton model.</p>

Yes / A major barrier to the systematic improvement of biomimetic peptide-mediated strategies for the controlled growth of inorganic nanomaterials in environmentally benign conditions lies in the lack of clear conceptual connections between the sequence of the peptide and its surface binding affinity, with binding being facilitated by noncovalent interactions. Peptide conformation, both in the adsorbed and in the nonadsorbed state, is the key relationship that connects peptide-materials binding with peptide sequence. Here, we combine experimental peptide–titania binding characterization with state-of-the-art conformational sampling via molecular simulations to elucidate these structure/binding relationships for two very different titania-binding peptide sequences. The two sequences (Ti-1, QPYLFATDSLIK; Ti-2, GHTHYHAVRTQT) differ in their overall hydropathy, yet via quartz-crystal microbalance measurements and predictions from molecular simulations, we show these sequences both support very similar, strong titania-binding affinities. Our molecular simulations reveal that the two sequences exhibit profoundly different modes of surface binding, with Ti-1 acting as an entropically driven binder while Ti-2 behaves as an enthalpically driven binder. The integrated approach presented here provides a rational basis for peptide sequence engineering to achieve the in situ growth and organization of titania nanostructures in aqueous media and for the design of sequences suitable for a range of technological applications that involve the interface between titania and biomolecules. / AFOSR grant FA9550-12-1-0226; AFOSR for funding via FA9550-13-1-0040

No / Chemical means of manipulating the distribution of lipids across biological membranes is of considerable interest for many biomedical applications as a characteristic lipid distribution is vital for numerous cellular functions. Here we employ atomic-scale molecular simulations to shed light on the ability of certain amphiphilic compounds to promote lipid translocation (flip-flops) across membranes. We show that chemically induced lipid flip-flops are most likely pore-mediated: the actual flip-flop event is a very fast process (time scales of tens of nanoseconds) once a transient water defect has been induced by the amphiphilic chemical (dimethylsulfoxide in this instance). Our findings are consistent with available experimental observations and further emphasize the importance of transient membrane defects for chemical control of lipid distribution across cell membranes

Les surfaces nanostructurées permettent d’obtenir des effets colorés gonio-apparents lorsque les nanostructures présentent des dimensions de l’ordre des longueurs d’onde du spectre visible. ces couleurs sont habituellement modélisées par le biais d’interactions de types «interférences» ou «cristaux photoniques» entre le rayonnement lumineux et une structure modèle. dans cette thèse, l’anodisation d’aluminium est utilisée comme méthode de structuration à l’échelle submicronique. cette technique présente l’avantage d’être mature industriellement et de permettre de structurer de grandes surfaces. des effets colorés sont observés même si les structures obtenues ne sont pas parfaitement ordonnées. le but de cette thèse est de comprendre les phénomènes optiques mis en jeu dans l’obtention de ces effets. ce manuscrit se divise donc en deux parties principales, toutes deux basées sur une étude de la littérature existante. afin d’établir un parallèle entre caractérisation expérimentale et simulation numérique, la première partie présente l’outil de caractérisation optique développé. la seconde est dédiée à l’étude des effets colorés de certaines surfaces d’aluminium anodisé. cette partie propose une compréhension des phénomènes d’interaction de la lumière avec la structure d’aluminium anodisé se basant sur les caractérisations optiques et microstructurales des échantillons, associées à une modélisation de l’interaction entre rayonnement et matière structurée. cette étude montre que les structures réelles présentent un ordre à courte distance. les effets colorés sont simulés par la méthode modale de fourier par le biais de structures modèles avec un certain niveau de désordre. / Nano-structured surfaces allow obtaining of colored gonio-apparent effects when the nano-structures dimensions are of the order of the visible spectrum wavelengths. these colors are usually modeled by means of the interactions type so-called « interferences type » ou « photonic crystals type » between the luminous radiation and a model structure. in this thesis, the anodization of aluminum substrates is used to produce surface structures at the submicron scale. this technique is industrially mature and allows to structure large surfaces. color effects were observed even if obtained structures are not perfectly ordered. the aim of this thesis is the understanding of the optical phenomena involved in the production of such effects. this manuscript is divided into two main parts, both based on the existing literature analysis. in order to draw a parallel between experimental characterization and numerical simulations, one part presents the instrumental development of the optical characterization instrument. the second one is dedicated to the study of color effect of certain anodized aluminum surfaces. this part proposes an understanding of the interaction phenomena between the light and the anodized aluminum structure, based on the optical and microstructural characterization of the samples, associated to a modeling of the interaction between light and structured matter. this study shows that such structures present a short-distance order. the color effects are simulated numerically by fourier modal method by the means of model-structures with certain disorder degree.

La dynamique instable des jets tournants est étudiée, en tenant compte des variations de masse volumique au sein de l'écoulement. Un code de simulation numérique directe permettant de résoudre les équations de Navier-Stokes à masse volumique variable a été développé, en utilisant une méthode originale et efficace pour résoudre le champs de pression. Analytiquement, deux modes instables bidimensionnels ont été mis en évidence, et sont identifiés comme des modes de Couette-Taylor et de Rayleigh-Taylor, ainsi qu'un troisième mode tridimensionnel, du à un couplage de vitesse. La dynamique instable de cet écoulement résulte d'une compétition entre ces trois modes, et les simulations numériques montrent que ces modes perdurent non linéairement. Ensuite, le comportement spatio-temporel de cette instabilité est étudiée par simulation numérique directe, et il a été montré qu'il existe une transition vers des modes absolument instables, sous l'effet du rapport de densité s ainsi que du taux de rotation q. Cette dynamique est également étudiée expérimentalement au travers de plusieurs méthodes de mesures, et la présence de mode globaux auto-entretenus est mise en évidence qui sont en bon accord avec les résultats numériques. Finalement, le phénomène de l'éclatement tourbillonnaire est étudié, et montre le rôle prépondérant de la viscosité réelle. En effet, l'éclatement tourbillonnaire est un mécanisme permettant de soulager le système de l'intensification de la vorticité, au travers de la viscosité, alors qu'il n'apparaît pas en traitant les équations d'Euler tronquées. / The unstable dynamics of a swirling jet flow is studied, including density variations within the flow. A direct numerical simulation method was developed to solve variable density Navier-Stokes equations, using an accurate and efficient pressure solver. Analitically, two unstable bi-dimensionnal modes are highlighted, and are identified as Couette-Taylor and Rayleigh-Taylor modes. A three-dimensionnal mode is also highlighted, wich is created by the shear. Numerical simulations show that those modes are nonlinearly persistant. Then, the spatio-temporal instability behaviour is studied numerically, and show that the instability undergoes to a convective/absolute transition with density ratio s and rotation rate q. This dynamic is also studied experiementally through different methods, and Global selfsustained modes are highlighted wich are in ggod agreement with numerical results. Finally, the vortex breakdown phenomenon is studied, and show the crucial role of real viscosity. Indeed, the vorticity intensification is relaxed through the viscosity effect, while it is not treating the truncated Euler Equations.

La formation et la morphologie des boîtes quantiques est un sujet d'un grand intérêt, ces structures ayant de nombreuses application potentielles, en particulier en microélectronique et optoélectronique. Cette thèse porte sur l'étude théorique et numérique de la croissance et de la morphologie d'ilots par épitaxie par jet moléculaire. Un premier modèle de croissance est une étude non-linéaire de l'instabilité de type Asaro-Tiller-Grinfeld, il convient pour les systèmes à faibles désaccords de maille, et est plus spécifiquement appliquée au cas où le désaccord de maille est anisotrope (voir le cas du GaN sur AlGaN). Le calcul de l'instabilité que nous avons effectué prend en compte les effets élastiques causés par le désaccord de maille, les effets de mouillage et les effets d'évaporation. La résolution numérique de l'instabilité nous permet de constater une croissance plus rapide dans le cas anisotrope comparé au cas isotrope, ainsi que la croissance d'ilots fortement anisotropes.Le deuxième modèle est basé sur des simulations Monte Carlo cinétiques, qui permettent de décrire la nucléation d'ilots 3D. Ces simulations sont utilisées pour les systèmes à fort désaccord de maille, comme Ge sur Si. Nos simulations prennent en compte la diffusion des adatomes, les effets élastiques, et un terme simulant la présence de facettes (105). Des ilots pyramidaux se formaent, conformément aux expériences et subissent un mûrissement interrompu. Les résultats obtenus ont été comparés au cas de la nucléation 2D, et on retrouve en particulier une densité d'ilots en loi de puissance par rapport au rapport D/F du coefficient de diffusion et du flux de déposition. / The growth and morphology of quantum dots is currently a popular subject as these structures have numerous potential uses, specifically in microelectronics and optoelectronics. Control of the size, shape and distribution of these dots is of critical importance for the uses that are being considered. This thesis presents a theoretical and numerical study of the growth of islands during molecular beam epitaxy. In order to study these dots, we used two models : a nonlinear study of an Asaro-Tiller-Grinfeld like instability, and kinetic Monte Carlo simulations. The first model is appropriate for low misfit systems, and is detailed in the case where misfit is anisotropic (this is the case when depositing GaN on AlGaN). In this case we took into account elastic effects, wetting effects and evaporation. Numerical calculations show faster growth, compared to the isotropic misfit case, and the growth of strongly anisotropic islands.The second model is based on kinetic Monte Carlo simulations that can describe 3D island nucleation. We use these simulations to study systems with high misfits, specifically Ge on Si. Adatom diffusion on a surface is considered and takes into account elastic effects, and surface energy anisotropy, that allows us to stabilize (105) facets. Simulation results show the growth of pyramid-shaped 3D islands, as observed in experiments, and their ripening is interrupted. The results of these simulations are then compared to the case of 2D nucleation, and we find that several of the known 2D properties also apply to 3D islands. Specifically, island density depends on a power law of D/F, the diffusion coefficient divided by the deposition flux.

La contribution des processus de fusion de galaxies lors de l'assemblage cosmologique de masses est encore mal comprise. Dans ce contexte, l'étude du support dynamique des galaxies est un moyen permettant de contraindre les différents scénarios d'évolution.Dans une première partie, je présente ma contribution à l'analyse cinématique des galaxies de l'échantillon MASSIV. Je définis une technique d'analyse qui vise à quantifier la fraction d'objets susceptibles d'être le produit d'une fusion.J'introduis dans une seconde partie une méthode de construction de conditions initiales de galaxies idéalisées.Dans une troisième partie, je présente la définition de l'échantillon de simulations MIRAGE, reproduisant les propriétés physiques des galaxies jeunes. Les simulations montrent en particulier l'absence de flambées de formation stellaire durant les fusions ce qui suggère un mécanisme de saturation.Une analyse des propriétés des complexes granulaires issus d'instabilités gravitationnelles est réalisée dans la quatrième partie, soulignant la compatibilité du scénario granules âgés avec les observations en terme de taux d'éjection de gaz et d'âge de populations stellaires. Je mets en évidence que le mécanisme de fusion de granules permet de contrôler la croissance de la masse du bulbe, d'aplatir le profil central de densité du halo de matière sombre ainsi que d'éjecter de grandes quantités de gaz.Dans une cinquième partie, je complète ce travail en réalisant une étude comparative des données cinématiques MASSIV à plus de 4000 pseudo-observations construites à partir des simulations de l'échantillon MIRAGE afin de déterminer la capacité à détecter des signatures de fusion. / The contribution of the fusion processes to the cosmological mass assembly is still poorly understood. In this context, the study of the dynamical support of galaxies is a way to constrain different evolution scenarios.In the first part, I introduce my contribution to the kinematical analysis of galaxies MASSIV. I define an analysis that aims at quantifying the fraction of objects that are likely to be the product of a recent merger.I introduce in the second part a method to build initial conditions of idealized galaxies.In the third part, I present the definition of the simulation sample MIRAGE, designed to reproduce the physical properties of young galaxies. The simulations show in particular the absence of a star formation bursts in mergers of fragmented and turbulent disks, suggesting a saturation mechanism.An analysis of the properties of clumps that are generated by gravitational instabilities is performed in the fourth part of this thesis, highlighting the compatibility of long-lived clumps scenarios with observations in terms of outflowing material and stellar population ages. I also highlight that the gas rich clump fusion mechanism is able to control the bulge mass growth, to erode the central profile of the dark matter halo and to drive massive gas outflows in the disk plane.Finally, in the fifth part, I complete this work by carrying out a comparative study of the MASSIV kinematical data to a set of more than 4000 pseudo-observations at z=1.7 built from simulations of the MIRAGE sample to determine the ability to detect galaxy merger signatures.

Lorsqu'un phénomène de détonation survient dans des milieux confinés comme un bâtiment présentant un système de galeries, l'onde de choc générée se propage et peut engendrer des dégâts matériels et humains considérables. En effet, l’onde de choc en se propageant dans ces systèmes de canaux confinés va interagir avec les obstacles qu’elle rencontre (humains et matériels), et va provoquer de très fortes élévations de la pression localement. Ce phénomène peut être très destructeur pour les structures et létale pour les humains. L'objectif de cette étude, expérimentale et numérique, est donc d'étudier la propagation d'une onde de choc dans différents systèmes de canaux afin de comprendre son comportement et de proposer des solutions pour en atténuer les dégâts. L’étude s’articule autour de deux grands axes. Le premier étudie de manière très académique la propagation d’une onde de choc au travers de cinq configurations différentes ; deux sans variation de section (un coude à 45$^{\circ}$ et un coude à 90$^{\circ}$), et trois avec variation de section (un divergent, un élargissement brusque et une bifurcation en « Y »). L’influence de la singularité sur la pression réfléchie en fond de configuration est étudiée ainsi que les mécanismes physiques complexes qui se produisent derrière l’onde de choc le long de la singularité. Le deuxième axe étudie l’atténuation de la pression réfléchie par l’ajout de piège (cavités) le long du système étudié. Une étude paramétrique montre que la position ainsi que la taille et la forme du piège ont un impact sur l’atténuation de l’onde de choc. / In the search for protection from explosions phenomena, a variety of underground shelters were studied to minimize the risks related to the propagation of shock waves in closed areas. Indeed, the blast effect could be really destructive for equipment and humans encountering the shock wave propagation, because of the high elevation of the local pressure it generates. Thus, the propagation of a shock wave through various canal systems is both experimentally and numerically studied. This study is based on two topics. The first part is focused on the study of the propagation of a shock wave through five various configurations ; two whithout aera change (a 45$^{\circ}$ bend duct and a 90$^{\circ}$ bend), and three configurations whith a sectional enlargement (a divergent, an abrupt area change and a « Y » bifurcation). The impact of the geometry on the end wall reflected pressure is studied as well as some complex physical mechanisms that occur behind the incident shock wave. The second part explores the mitigation of the pressure level in the device with the addition of traps (cavities) along the studied configuration. A parametric study based on the shape and size of the cavities, shows that these parameters have a considerable impact on the pressure level in the duct system.