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Goel, Archak. "Design of Functionally Graded BCC Type Lattice Structures Using B-spline Surfaces for Additive Manufacturing." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1552398559313737.
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Gilbert, Mark R. "BCC metals in extreme environments : modelling the structure and evolution of defects." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:d972d28d-5d2d-4392-8cf5-fc5728dc74f6.
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Designing materials for fusion applications is a very challenging problem, requiring detailed understanding of the behaviour of materials under the kinds of extreme conditions expected in a fusion environment. During the lifetime of fusion-reactor components, materials will be subjected to high levels of neutron irradiation, but must still perform effectively at high operating temperatures and under significant loading conditions. Body-centred cubic (bcc) transition metals are some of the most promising candidates for structural materials in fusion because of their relatively high density, which allows for effective neutron-shielding with the minimum volume and mass of material. In this work we perform atomistic simulations on two of the most important of these, Fe and W. In this thesis we describe atomic-scale simulations of defects found in bcc systems. In part I we consider the vacancy and interstitial loop defects that are produced and accumulated as a result of irradiation-induced displacement cascades. We show that vacancy dislocation loops have a critical size below which they are highly unstable relative to planar void defects, and thus offer an explanation as to why they are so rarely seen in TEM observations of irradiated bcc metals. Additionally, we compare the diffusion rates of these vacancy loops to their interstitial counterparts and find that, while interstitial loops are more mobile, the difference in mobility is not as significant as might have been expected. In part II we study screw dislocations, which, as the rate limiting carriers of plastic deformation, are significantly responsible for the strength of materials. We present results from large-scale finite temperature molecular dynamics simulations of screw dislocations under stress and observe the thermally-activated kink-pair formation regime at low stress, which appears to be superseded by a frictional regime at higher stresses. The mobility functions fitted to the results are vital components in simulations of dislocation networks and other large-scale phenomena. Lastly, we develop a multi-string Frenkel-Kontorova model that allows us to study the core structure of screw dislocations. Subtle changes in the form of the interaction laws used in this model demonstrate the difference between the non-degenerate and degenerate core structures. We provide simple criteria to guarantee the correct structure when developing interatomic potentials for bcc metals.
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Rashetnikava, Alena, Alexander Germanov, Irina Valikova, and Andrei Nazarov. "Molecular dynamics simulation of atomic structure in the vicinity of point defects in FCC and BCC metals." Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-190156.
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Rashetnikava, Alena, Alexander Germanov, Irina Valikova, and Andrei Nazarov. "Molecular dynamics simulation of atomic structure in the vicinity of point defects in FCC and BCC metals." Diffusion fundamentals 11 (2009) 52, S. 1-2, 2009. https://ul.qucosa.de/id/qucosa%3A14014.
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Červinek, Ondřej. "Výpočtový model dynamického zatěžování mikro-prutové struktury vyrobené technologií Selective Laser Melting." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2018. http://www.nusl.cz/ntk/nusl-379040.
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For the purpose of mechanical impact energy absorption in the transport industry are mainly used special profile absorbers. For highly specialized applications is required to use components that are designed for specific kind of deformation. Example of these parts are industrial-made metal foams or micro-lattice structures produced by SLM technology. This paper focuses on low-velocity dynamic loading prediction of BCC micro-lattice structure made of aluminum alloy AlSi10Mg by SLM technology (SLM 280HL). For this purpose dynamic FEM simulaton of the micro-lattice structure was developed, supplemented by model of BCC structure material obtained from mechanical testing. Real geometry of tested samples obtained from optical measurement (Atos Triple Scan III) was further implemented in the numerical model. Dynamic BCC structure load experiment was performed on a drop-weight tester. Behavior of structured material in drop-weight test was described by the course of deformation and reaction forces over time. Comparable results were obtained for flat loading of dynamic FEM simulation and experiment. Inclusion of production phenomena in simulation led to increased accuracy and compliance with experiment. Tool for testing the effect of geometry change on mechanical properties was created. To achieve more accurate results with puncture load, it is necessary to modify the material model with real material deformation at test sample failure.
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Al-wattar, Tahseen Abdulridha Ali. "Developing equivalent solid model for lattice cell structure using numerical approaches." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1610335304435815.
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Gorondy, Novak Sofia Maria. "Etude du comportement de l'hélium dans les structures cubiques centrées pour les nouvelles générations de réacteurs nucléaires : approche expérimentale dans le cadre de matériaux modèles." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066537/document.
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La présence de l’hélium induite par le fonctionnement des futurs réacteurs à neutrons rapides et à fusion dans les matériaux de cœur peut entrainer une dégradation de leurs propriétés mécaniques (durcissement, gonflement, fragilisation). Pour poursuivre le développement des alliages de structure, il est nécessaire d’acquérir une meilleure compréhension de l’interaction entre l’He et les structures métalliques donc le point en commun est de comporter comme métal de base un élément de cristallographie cubique centrée (CC), notamment le fer et le vanadium.L’implantation ionique d’ions 4He a été utilisée pour simuler les effets d’endommagement liés à l’insertion d’He, la création des défauts ponctuels (lacunes, interstitiels) et la formation des amas hélium-lacunes dans les futurs réacteurs. L’évolution du comportement de l’He dans le fer et le vanadium purs a été mise en évidence tant du point de vue de la nature des sites de piégeage que du point de vue des mécanismes de migration de l’He et de germination et croissance de bulles associés, en s'appuyant sur un couplage original de techniques. Les résultats obtenus mettent en avant une différence de comportement entre les deux métaux CC, bien que certains mécanismes impliqués soient similaires. Les défauts microstructuraux, notamment les joints de grains, et la concentration d’He implantée (fluence) joueront des rôles clés sur le comportement de l’He à haute température.Les données expérimentales acquises couplées avec des méthodes de simulation serviront de point de départ pour développer une approche cinétique et thermodynamique du comportement de l’He dans les éléments constitutifs des alliages d’intérêt nucléaireThe presence of helium produced during the operation of future fast reactors and fusion reactors in core structural materials induces a deterioration of their mechanical properties (hardening, swelling, embrittlement).In order to pursue the development of the metallic structural alloys, it is necessary to comprehend the He interaction with the metal lattice thus the point in common is the study of the metallic components with body-centered cubic structure (bcc) of future alloys, such as iron and/or vanadium.Ion implantation of ions 4He was employed with the aim of simulating the damaging effects associated with the helium accumulation, the point defects’ creation (vacancies, self-interstitials) and the He cluster formation in future reactors. Helium evolution in pure iron and pure vanadium has been revealed from the point of view of the trapping sites’ nature and well as the helium migration mechanisms and the nucleation/growth of bubbles. These phenomena were studied by coupling different complementary techniques. Despite of the fact that some mechanisms involved seem to be similar for both bcc metals, the comparison between the helium behavior in iron and vanadium shows certain differences. Microstructural defects, including grain boundaries and implanted helium concentration (dose) in both bcc metals will play significant roles on the helium behavior at high temperature.The acquired experimental data coupled with simulation methods contribute to the future development in terms of kinetic and thermodynamic data management of helium behavior in the metal components of the alloys of nuclear interest
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Keerthi, Sandeep. "Low Velocity Impact and RF Response of 3D Printed Heterogeneous Structures." Wright State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright1514392165695378.
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DOQUET-DARIDON, VERONIQUE. "Comportement et endommagement de deux aciers a structure cubique centree et cubique a faces centrees, en fatigue oligocyclique, sous chargement multiaxial non-proportionnel." Paris, ENMP, 1989. http://www.theses.fr/1989ENMP0137.
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Precision des mecanismes de durcissement cyclique anormal manifeste par certains materiaux sous chargement non proportionnel, ainsi que des reductions d'endurance qui l'accompagnent. Etude dans le cas de l'acier inoxydable austenitique 316 l et d'un acier doux
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Schneider, Andreas Simon [Verfasser]. "Mechanical properties of small scale BCC metal structures / vorgelegt von Andreas Simon Schneider." Stuttgart : Max-Planck-Inst. für Metallforschung, 2010. http://d-nb.info/1004952171/34.
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Brookes, Richard. "Structure and dynamics in network liquids." Thesis, University of Oxford, 2002. http://ora.ox.ac.uk/objects/uuid:af233937-3168-498a-b7cc-eed758f5e5de.
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The onset of the Glass Transition in tetrahedral network liquids is associated with the over-constrained nature of the structure and the low ability of the ions to move relative to one another. We investigate the interplay between the structure and dynamics in BeF2, a template for the ideal tetrahedral system. We see that the ionic diffusion coefficients can be predicted from the calculated viscosity of the system using the Eyring hopping model of diffusion, with a diffusive jump length approximately corresponding to the radius of the first coordination sphere. Novel correlation functions are developed which enable us to identify the events responsible, on an atomistic level, for the structural rearrangements which correspond to the barrier crossing in this hopping model of diffusion, and we find that these events can be identified as the exchange of ions in the local coordination poly- hedra, or cage, of the cations. The calculation of the rate of the decay of these cages allows us to predict the macroscopic diffusion coefficients with the definition of a jump length over which the diffusive hops occur, and to scale the behaviour of the system at different temperatures by setting the cage lifetime as an effective clock for the system. Comparison between simulations performed with and without the inclusion of the effects of anion polarisation suggest that the polarisation plays an important role in the ability of the system to undergo the cage decay events and to create the defect sites which facilitate a decrease in the number of constraints acting in the system. The decay of the cages describes the local rearrangement of the ions in the first coordi- nation shell of a given ion. The development of other correlation functions allows us to investigate the spatial relationship between these cage decay events over longer length and time scales, and also to investigate how the local structure of the first coordination shells of the cations relates to their ability to undergo the cage decay events and to form the defects. These functions are then used to investigate the link between the structure and the dy- namics in some molten trichloride systems, which have different network structures, and hence a different relationship between the cage decay and the diffusion. Finally, we investigate the effect of changing the potential parameters in BeF2, and we find that the effective polarisability of the system can be controlled such that a less diffusive system may be described, giving a good representation of both structural and dynamical experimental data.
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Abdulhadi, Hasanain. "Designing New Generations of BCC Lattice Structures and Developing Scaling Laws to Predict Compressive Mechanical Characteristics and Geometrical Parameters." Wright State University / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=wright1610335306482598.
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Hamid, Sami. "On the structure of a class of operators." Diss., Texas A&M University, 2005. http://hdl.handle.net/1969.1/2354.
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In this dissertation we study certain classes of operators on a separable, complex,
in??nite dimensional Hilbert space H, speci??cally from the point of view of properties
of the hyperlattice (i.e., lattice of hyperinvariant subspaces) for such operators. We
show that every (BCP)-operator in C00 is hyperquasisimilar to a quasidiagonal (BCP)-
operator in C00. Moreover we show that there exists a ??xed block diagonal (BCP)-
operator Bu with the property that if every compact perturbation Bu + K of Bu in
(BCP) and C00 with kKk < " has a nontrivial hyperinvariant subspace, then every
nonscalar operator on H has a nontrivial hyperinvariant subspace. This shows that
the study of the structure of the hyperlattice of an arbitrary operator on Hilbert
space is essentially equivalent to the study of the hyperlattice structure of some much
smaller, special classes of operators, and it is these on which we concentrate.
Moreover, we study some special subclasses (B??) and (S??) of the class of in-
vertible (BCP)-operators with a view of obtaining some insight into the problem of
determining the structure of operators in these classes.
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Kowalewski, Maciej Matthew Zbigniew. "Engineering and investigation of the interlayer exchange coupling in bcc Fe/Cu/Fe(001) structures." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0020/NQ37722.pdf.
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Tuffal, Gilles. "Analyse structurale et fonctionnelle des lipopolyméthylglucoses de Mycobacterium bovis BCG." Toulouse 3, 1995. http://www.theses.fr/1995TOU30281.
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La paroi des mycobacteries joue un role majeur dans la survie intramacrophagique des mycobacteries pathogenes telles que mycobacterium tuberculosis, l'agent etiologique de la tuberculose. Elle contient une forte proportion d'acides mycoliques, supposes former une barriere physique relativement impermeable aux molecules hydrophiles et en particulier aux antibiotiques polaires. Bien que les etapes clef de la biosynthese des acides mycoliques soient connues, aucun schema de biosynthese ne specifie l'origine des acides gras precurseurs. Ces derniers pourraient provenir du cytoplasme ou leur biosynthese est catalysee par l'acide gras synthetase de type i (ags i), une enzyme dont l'activite est modulee par des polysaccharides partiellement methyles: les lipopolymethylglucoses (lpmg) et les polymethylmannoses (pmm). L'analyse structurale des lpmg, realisee auparavant chez m. Smegmatis, a ete reprise sur la base de resultats de spectrometrie de masse indiquant que les pmg (la structure polysaccharidique des lpmg) de m. Bovis bcg forment un melange. Celui-ci a ete resolu en utilisant la chromatographie liquide d'echange d'anions a haut ph, chaque pmg purifie etant analyse par spectrometrie de masse. Cette strategie analytique nous a permis de caracteriser une dizaine de pmg isoles chez m. Bovis bcg ainsi que chez d'autres mycobacteries, se differenciant par leur degres de polymerisation et leur taux de methylation. Elle a aussi revele des differences de distribution des pmg entre souches a croissance rapide et lente. De plus, l'analyse par resonance magnetique nucleaire bidimensionnelle des pmg a permis de redefinir leur structure generale et surtout d'elucider la structure d'un nouveau compose present chez m. Bovis bcg, contenant un residu de 2-n-acetamido-2,6-didesoxy-glucopyranose. Dans le but de mieux cerner les proprietes des lpmg, les complexes stoechiometriques lpmg/palmityl-coa ont ete analyses en utilisant l'electrophorese capillaire couplee a la spectrometrie de masse
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Gaspard, Vincent. "Interactions Hydrogène – Plasticité dans les Alliages Ferritiques." Thesis, Saint-Etienne, EMSE, 2014. http://www.theses.fr/2014EMSE0730/document.
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Le développement à grande échelle des projets de véhicules électriques à pile àcombustible nécessite le déploiement d’infrastructures de transport et de stockaged’Hydrogène gazeux. La conception de ces structures et la sélection des matériaux nécessitede s’affranchir des risques liés à la fragilisation par l’Hydrogène des alliages métalliques. Cephénomène est bien décrit depuis plusieurs décennies, mais les mécanismes élémentaires àl’origine de ce mode d’endommagement restent controversés, notamment par manque demodèles quantitatifs. Plus précisément, le rôle de la déformation (micro-)plastique en pointede défaut sur le piégeage et l’endommagement par l’hydrogène, s’il est bien démontréexpérimentalement dans de nombreux systèmes, reste mal pris en compte dans les modèlesmicro-mécaniques. Le centre SMS de l’ENSM.SE a proposé des approches originales demodélisation des interactions hydrogène – dislocations, qui ont pu être validéesexpérimentalement dans des matériaux modèles de structure cubique à faces centrées. Cette thèsese propose d’appliquer une démarche semblable dans des alliages de structure cubiquecentrée. On mettra en oeuvre des essais de déformation sur des matériaux modèles pré-chargésen hydrogène, des modèles semi-analytiques et des observations des structures de déformationen microscopie électronique à transmissionThe development of electrical vehicles powered by hydrogen fuel cells requires the large scaledeployment of hydrogen storage and transport infrastructures. This in turn requires theassessment of the sensitivity of structural materials to hydrogen embrittlement phenomena.These damage modes, while being well described experimentally for since several decades,are still highly debated when it comes to elementary physical processes, mainly because of thelack of quantitative models for these elementary processes. More precisely, the role of the(micro-)plasticity developing at the tip of structural defects, while being well establishedexperimentally, is still poorly accounted for in the available micro-mechanical models. TheScience of Materials and Structures division of ENSM.SE already proposed originalmodelling approaches for hydrogen – dislocation interactions, that have been experimentallyvalidated in face-centred cubic materials. This project aims at applying the same type ofapproach to body-centred cubic metals. This will be achieved by means ofdeformation tests on hydrogen-charged model body centred cubic alloys, investigations of thedislocation microstructures by transmission electron microscopy and the development ofsemi-analytical models of hydrogen-dislocation interactions
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Marshall, Bryan Jonathan. "Wind flow structures and wind forces in forests." Thesis, University of Oxford, 1998. http://ora.ox.ac.uk/objects/uuid:16f42b9c-a87c-43f9-bcc3-def409aa61d5.
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This thesis describes a series of 1:75 scale wind tunnel experiments investigating the wind flow over, and through, three different forest models and the resultant wind loading on individual model trees. The experiments were designed to lead to a quantitative assessment of the wind stability of the particular forest arrangements and also to permit a study of the coherent gust structures in the flow. Forest canopy flow is dominated by a plane mixing layer flow regime with a shear layer close to the canopy top. It has been confirmed that data can be correlated usefully in terms of a shear length, Ls, related to the form of this shear layer. Frequency analysis has confirmed that the flow structures have the same frequency as the swaying of the tallest trees in each forest. A mechanism is proposed whereby upstream turbulence induces swaying of trees at and near the upwind edge region of the forest, which in turn perturbs the air in the unstable shear layer. This leads to a roll-up of the shear layer and the creation of coherent flow structures. Conditional sampling of the gust structures, using wavelet analysis, has also supported the theory of a plane mixing layer type flow. An eddy-pair structure was revealed, the arrangement of which accounts for the intermittent strong downward sweeps of air into the canopy that have been reported by many observers. The large downward sweep of air was also shown to be responsible for the highest bending moments experienced by individual trees. Assessments of the different forest formations showed that in a forest consisting of a 50/50 mix of 200 mm and 100 mm model trees, gusts did not penetrate the lower forest. This arrangement should improve the protection of younger trees and may be worth investigating in field trials.
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Fontaine, Edward. "Transitioning BBC from a program-based structure to a cell-based structure for doing evangelism and discipleship." Theological Research Exchange Network (TREN), 2006. http://www.tren.com/search.cfm?p006-1491.
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Forest, Richard C. "Structures and metamorphism of Ptarmigan Creek area, Selwyn Range, B.C." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63337.
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Lellis, Leandro. "An organizational structure analysis for BC Hydro, Power Smart /." Burnaby B.C. : Simon Fraser University, 2006. http://ir.lib.sfu.ca/handle/1892/3523.
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Research Project (M.B.A.) - Simon Fraser University, 2006.Theses (Faculty of Business Administration) / Simon Fraser University. MBA-MOT Program. Senior supervisor : Dr. Sudheer Gupta. Also issued in digital format and available on the World Wide Web.
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Liu, Qian. "Structural insights into apoptotic regulation by BCL-2 family." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=95022.
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Myeloid cell leukemia 1 (MCL-1), an anti-apoptotic BCL-2 member, is active in the preservation of mitochondrial integrity during apoptosis. By collective data from nuclear magnetic resonance (NMR) spectroscopy and titration calorimetry, we revealed the selectivity of MCL-1 in binding BH3 ligands of interest to mammalian biology, and proved that the core domain of MCL-1 (cMCL-1) is necessary and sufficient for BH3 ligand binding. We characterized the in vitro protein-protein interaction between cMCL-1 and activated BID, which occurs in a very slow manner in solution but is otherwise similar to the interaction between cMCL-1 and BID-BH3 peptide. We also present the solution structure of complex cMCL-1:BID-BH3, which may greatly facilitate drug discovery studies of human tumor malignancies. BAK, a multi-region pro-apoptotic protein, directly mediates the mitochondrial outer membrane permeablization (MOMP). We completed a structural investigation of BAK by X-ray crystallography. We report two structures of BAK's homo-dimers, one zinc-mediated (cBAK) and one disulphide-bond-linked (cBAK-o). Their dimerizing sites locate closely at D160 and H164 in cBAK and C166 in cBAK-o, which allow them to compose a unique regulatory element to switch BAK's activity as suggested in mitochondria activity-testing assays. BAK is tightly regulated through protein-protein interactions by MCL-1. We characterize the conformational changes in BAK and MCL-1 using detergents to mimic the membrane environment, and studied their interaction in vitro. The non-ionic detergent IGEPAL and the zwitterionic detergent CHAPS have different effects on these two proteins, but both initiate the heterodimerization. The complex of MCL-1 and BAK can be disrupted by either a BID-BH3 peptide, which acts through binding to MCL-1, or a mutation in BH3 region of BAK (L78A), demonstrating the essential role of BAK's BH3 in its regulation by MCL-1. This thesis concludes with a hybrid model for BAK activation:La protéine MCL-1 (Myeloid cell leukemia 1), qui appartient à la classe de protéines anti-apoptotiques BCL-2, joue un rôle dans le maintien de l'intégrité mitochondriale durant l'apoptose. Les résultats obtenus par résonance magnétique nucléaire (RMN) et par titrage calorimétrique, nous ont permis de mettre en évidence la sélectivité de la protéine MCL-1 pour les ligands mammifères d'interêt biologiques qui contiennent le motif BH3 et nous avons ainsi démontré que le domaine central du facteur MCL-1 (cMCL-1) est nécessaire et suffisant pour cette interaction. Nous avons caractérisé in vitro l'interaction entre le domaine cMCL-1 et le facteur activé BID; cette interaction se produit lentement en solution mais est similaire à celle observée entre le domaine cMCL-1 et le peptide BID-BH3. De plus nous avons résolu la structure du complexe cMCL-1:BID-BH3, qui est une cible potentielle qui pourrait être à la base d'un criblage d'une banque de petites molécules dans le cas de tumeurs humaines malignes. BAK, une protéine pro-apoptotic modulaire, permet la perméabilité de la membrane externe de la mitochondrie: ce mécanisme est dénommé MOMP pour the mitochondrial outer membrane permeablization. Nous avons accompli l'étude structurale de la protéine BAK par cristallographie et diffraction de rayons X. Nous présentons deux complexes de la protéine BAK: un homodimère lié par une molécule de zinc (cBAK) et une qui contient un pont disulfure (cBAK-o). Le site de dimérisation se situe proche des résidu D160 et H164 pour cBAK et C166 pour cBAK-o, ce qui leur confère un élément de régulation unique pour moduler l'activité de BAK comme suggéré dans des essais d'activité mitochondriale. La protéine BAK est finement régulée grâce à son interaction protéine-protéine avec MCL-1. Nous avons caractérisé les changements conformations des facteurs BAK et MCL-1 à l'aide de détergents pour modéliser un environnement m
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Moore, Catrin Elisabeth. "Case-control study of invasive Staphylococcus aureus disease-host genetic susceptibility and bacterial population structure." Thesis, University of Oxford, 2002. https://ora.ox.ac.uk/objects/uuid:85a3a6b4-b0cc-48ed-b584-5037ea884250.
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Staphylococcus aureus is a major pathogen associated with serious community-acquired and nosocomial disease. It is carried nasally at some time by 70% of the population, yet severe disease is relatively uncommon. Two case-control studies were conducted in Oxford, UK and Thailand to examine bacterial and host genetic determinants of severe S. aureus disease. Over 800 cases and 1,600 healthy control individuals were recruited into the two studies. The genetic population structures of S. aureus disease and carriage isolate populations from the Oxford study were studied and compared using phage typing, pulsed-field gel electrophoresis, and multilocus sequence typing. Natural populations of S. aureus have a well-defined clonal population structure, but there was no evidence for the existence of hypervirulent clones. The presence or absence of 33 putative bacterial virulence determinants was examined. After adjusting for the effect of clonality, seven determinants (fhbA, cna, sdrE, sej, eta, hlg and ica) were significantly more common in invasive isolates; all contributed independently to virulence. In the host genetic studies a functional single nucleotide polymorphism at amino acid position 131 of the Fc gamma receptor IIA (FcyRIIA) gene was significantly associated with severe disease. In addition an additive x additive epistatic interaction was found between this FcyRIIA polymorphism and the functional FcyRIIIB NA1/NA2 polymorphism. These significant associations were present when community-acquired disease cases were considered alone, but absent in hospital-acquired disease cases. The putatively functional polymorphisms in genes coding for mannose binding lectin and Tolllike receptor 2 were not associated with disease. Both bacterial and host factors are important in determining the occurrence of severe S. aureus disease. In hospital-acquired infection it is likely that acquired host, bacterial and environmental factors predominate, lessening the importance of any host genetic component.
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Zafeiriadis, Paschalis. "Society Makes Itself: Analyzing Spatial and Social Structures in Late Neolithic (ca. 5300-4500 B.C.) – Early Bronze Age (ca. 3300-2000 B.C.) Macedonia, Greece." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1543847743106245.
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Doucet, Jeremy. "Fatigue life enhancement of aircraft structures through bonded crack retarders (BCR)." Thesis, Cranfield University, 2015. http://dspace.lib.cranfield.ac.uk/handle/1826/11279.
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The trend in aircraft design is to produce greener airplanes through lighter structures and/or structures with extended life and reduced maintenance. Bonded crack retarders (BCR) are one of the solutions towards that objective. BCR are reinforcing straps bonded to the structure in order to improve the fatigue and damage tolerance properties of the assembly. The aim of this study was to demonstrate that the BCR hybrid technology – beneficial for upper wing cover – could also be applied to lower wing covers. The project also focused on evaluating BCR most important parameters. The fatigue life improvement obtained from BCR was evaluated through a series of coupons and skin-stringer assemblies tested under constant and variable amplitude loading. While the coupon tests demonstrated a life improvement of only 17% under constant amplitude loading, the variable amplitude load tests performed on the skin-stringer assembly demonstrated increased fatigue lives with a factor of 5 and reduced crack growth rates with a factor of 5 to 6. A finite element calculation tool was developed in order to conduct a parametric analysis of BCR geometry through the evaluation of the substrate stress intensity factor in the case of fatigue loading. The main difficulty was to include the interacting mechanism of the substrate lead crack and the disbond of the adhesive layer. The novelty of the approach was to incorporate the fatigue delamination calculation in order to evaluate the fatigue disbond propagation with crack growth. This was embedded in a 3D finite element design tool ReSLIC (Reinforced Structures Life Improvement Calculation). A necessary step to the development of ReSLIC was the analysis of fatigue properties of the adhesive system in order to provide input data for fatigue delamination calculations. To that end, a series of fatigue tests were performed in pure Mode I, pure Mode II and mixed mode with ratios of 25%, 50% and 75% of mode II ... [cont.].
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Whittle, Jessica Kaye. "Strategic placement of viscous dampers for seismic structural design." Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:58ea0592-a6de-438d-bc8c-5cc3cf1cf9ea.
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Seismic design with viscous devices is an effective means of dissipating seismic energy and protecting the main structural system from permanent damage. Despite numerous damper placement methods available, there lacks consensus on the best method, thus leaving design engineers without recommended placement strategies. The purpose of this research is to investigate strategic placement of viscous dampers for seismic design and to offer design recommendations for placing dampers, vertically and horizontally. Five damper placement techniques were selected for investigation, including standard methods, Uniform and Stiffness Proportional damping, and advanced methods, the Simplified Sequential Search Algorithm (SSSA method), the Optimal Damper Placement for Minimum Transfer Functions (Takewaki method), and the Fully-stressed Analysis/Redesign method (Lavan A/R method). Effectiveness of the techniques for distributing linear fluid viscous dampers for two building examples was evaluated under a suite of twenty ground motions, two seismic hazard levels, and in terms of peak interstorey drifts, absolute accelerations, and residual drifts using nonlinear time history analysis. The advanced methods showed comparable performance based on performance indicators. Therefore, usability is recommended as the selection criteria. The Lavan A/R method was found to be the most effective and usable method. It is recommended that multiple design ground motions be used for the SSSA Mode and Lavan A/R methods as well as caution against removal of upper storey damping, which prompts susceptibility to larger roof drifts due to higher-mode effects. Various brace-damper arrangements were explored to determine strategic horizontal damper placement. It was found that brace-damper arrangements with diagonals and multiple brace- damper sets per floor pose effective means of distributing the axial damper force and protecting the lower-storey columns from overstressing. Behavioural testing of two nonlinear viscous devices was performed, and results were used to determine analytical models for the nonlinear fluid viscous and fluid spring devices based on fitted parameters. It was found that the stress-relaxation models better captured the nonlinearity of the devices than standard models but yielded only marginally decreased energy dissipation per cycle. Thus, it is recommended that standard models are adequate for analysis of damped structures with these nonlinear viscous devices.
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Soares, Kelen Pureza. "O GÊNERO Butia (BECC.) BECC. (ARECACEAE) NO RIO GRANDE DO SUL COM ÊNFASE NOS ASPECTOS ECOLÓGICOS E SILVICULTURAIS DE Butia yatay (MART.) BECC. e Butia witeckii K. SOARES & S. LONGHI." Universidade Federal de Santa Maria, 2013. http://repositorio.ufsm.br/handle/1/8721.
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The aim of this work was show two studies. The first one consisted of a survey on indigenous Butia from Rio Grande do Sul. Through observations of morphological characteristics, eight species were recognized (B. catarinensis Noblick & Lorenzi, B. eriospatha (Mart. ex Drude) Becc., B. exilata Deble & Marchiori, B. lallemantii Deble & Marchiori, B. odorata (Barb. Rodr.) Noblick, B. paraguayensis (Barb. Rodr.) L. H. Bailey, B. witeckii K. Soares & S. Longhi and B. yatay (Mart.) Becc.). Three were considered synonyms (B. missionera Deble & Marchiori, B. pulposa (Barb. Rodr.) Nehrl. and B. quaraimana Deble & Marchiori). B. microspadix Burret and B. stolonifera (Barb. Rodr.) Becc. was not confirmed from Rio Grande do Sul. Figures with geographical distribution, key of identification, illustrations, and comments about the biology and taxonomy of each species were provided. The second study evaluated the ecological characteristics and productive and reproductive potential of two jelly palm populations from Rio Grande do Sul, with a population of B. yatay species (from Coatepe Quaraí) and another of B. witeckii species (from Quebra-dentes Quevedos/Júlio de Castilhos). In an area of 1 ha of the first species and 2 ha of the second species, respectively 79 and 34 mature palms were found. The characterization of the number of fruits per inflorescence was based on a sample of 80 and 84 infructescenses, respectively of the B. yatay and B. witeckii species. The biometric characterization of the fruits was based on a sample of 240 and 360 fruits, respectively for the B. yatay and B. witeckii species, separated by crop and plot. The hypsometric distribution shows that two populations are seriously threatened due to lack of natural regeneration, predated by cattle. Both species showed some significant differences between biometric parameters in adult trees (except the stem circumference and number of inflorescences in B. witeckii) and their fruit, when comparing the different plots. Positive correlations were found between biometric parameters of plants and of the fruits. Biometric parameters of the palmtrees are correlate with ecological parameters observed. There was an increase in the production of fruit pulp in the year 2012 when compared with 2011 on two species.Several factors seem to influence productivity, such as weather conditions, performance of pollinators, age/size of palm, physical and chemical characteristics of the soil and density of reproductive plants. The productivity of pulp and viable seeds per adult palm shows significant difference between two species, 10.31 kg and 12.96 kg of pulp and 1388 and 1075 viable seeds per palm, respectively, for B. yatay and B. witeckii. The two species have great productive potential.O objetivo deste trabalho foi o de realizar dois estudos. O primeiro consistiu no levantamento das espécies de Butia nativas do Rio Grande do Sul e, através de observações das características morfológicas, foram confirmadas oito espécies: B. catarinensis Noblick & Lorenzi, B. eriospatha (Mart. ex Drude) Becc., B. exilata Deble & Marchiori, B. lallemantii Deble & Marchiori, B. odorata (Barb. Rodr.) Noblick, B. paraguayensis (Barb. Rodr.) L. H. Bailey, B. witeckii K. Soares & S. Longhi e B. yatay (Mart.) Becc. Além disso, três foram consideradas sinonímias: B. missionera Deble & Marchiori, B. pulposa (Barb. Rodr.) Nehrl. e B. quaraimana Deble & Marchiori. B. microspadix Burret e B. stolonifera (Barb. Rodr.) Becc. não foram confirmadas para a flora sul-riograndense. Foram fornecidas figuras com a distribuição das espécies no estado, chave de identificação, ilustrações, e comentários acerca da biologia e da taxonomia de cada espécie. O segundo estudo avaliou os aspectos ecológicos e silviculturais de Butia yatay e Butia witeckii, sendo uma população de B. yatay, localizada na região de Coatepe Quaraí, RS, e, outra, da espécie B. witeckii, na região de Quebra-dentes Quevedos/Júlio de Castilhos, RS. Em uma área de 1 ha da primeira espécie e de 2 ha da segunda, foram registradas respectivamente 79 e 34 plantas adultas. A caracterização do número de frutos por infrutescência foi baseado numa amostra de 80 e 84 infrutescências, respectivamente das espécies B. yatay e B. witeckii. A caracterização biométrica dos frutos foi baseada numa amostra de 240 e 360 frutos, respectivamente para as espécies B. yatay e B. witeckii, sendo separadas por safra e por parcela. A distribuição hipsométrica mostrou que as duas populações estão seriamente ameaçadas devido à ausência de regeneração natural, uma vez que as plântulas são predadas pelo gado bovino. Nas duas espécies, houve diferenças significativas entre as estruturas biométricas das plantas adultas (exceto circunferência do estipe e número de infrutescências em B. witeckii) e dos seus frutos, quando se comparou as diferentes parcelas de cada população. Foram encontradas correlações positivas entre as estruturas biométricas das plantas e dos frutos. As estruturas biométricas das plantas apresentaram correlações com os dados ecológicos avaliados. Houve um aumento na produção de polpa dos frutos no ano de 2012 em relação ao ano anterior nas duas espécies; diversos fatores parecem influenciar a produtividade, como condições climáticas, atuação dos agentes polinizadores, idade/porte das palmeiras, características físicas e químicas do solo e densidade de plantas reprodutivas. Entre as espécies, a produtividade de polpa e sementes viáveis apresentou diferença significativa, sendo 10,31 kg e 12,96 kg de polpa e 1388 e 1075 sementes viáveis por butiazeiro, respectivamente para B. yatay e B. witeckii. As duas espécies apresentam grande potencial produtivo.
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Mohamed, Mahmoud Ould Ahmédou. "Etude structurale du carbure de bore (BC3) et du carbonitrure de bore (BNC2). : Approche expérimentale (spectroscopie photoélectronique à rayonnement X) et théorique." Pau, 1997. http://www.theses.fr/1997PAUU3005.
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Etude des propriétés structurales et électroniques des composés de type BC#3 et BNC#2. Un volet expérimental développe autour de la spectroscopie photoélectronique à rayonnement X (XPS) une approche théorique couplée aux résultats expérimentaux. L'analyse XPS de ces composés BC#3 et BNC#2 a nécessité la détermination préliminaire des spectres de composés de référence (graphite, nitrure de bore hexagonal, bore métallique et les carbures de bore b#1#3C#2 et B#4C). L'analyse XPS des composés de types BC#3 a montré la présenceé: - de deux pics caracteristiques, un pic CLS à 282. 7 EV et un pic B1S à 188. 5 EV. Ils rendent compte de l'existence d'atomes de bore venant se substituer à des atomes de carbone dans les plans de graphene. - D'une bande B1S à 186. 9 EV caractéristique d'un atome de bore dans un environnement d'atomes de bore montrant l'existence d'agrégats de bore. Les dépôts de carbonitrures de bore BNC sont caractérisés par : - deux pics CLS, l'un à 283 EV et l'autre à 285. 6 EV respectivement associés à un atome de carbone ayant comme voisin soit un atome de bore soit un atome d'azote ; - un pic B1S à 188. 9 EV et un pic N1S à 399. 4 EV attribués aux environnements respectifs : N#2BC et B#2NC ; ces deux pics peuvent être interprétés comme résultant de la substitution d'atomes de carbone par des atomes de bore et d'azote dans le réseau graphitique. - la présence de pics B1S (190. 3 EV) et N1S (397. 7 EV) associés à du nitrure de bore. Les résultats de calculs précisent pour ces systèmes les possibilités d'insertion d'atomes étrangers dans les plans de graphene ; dans chaque cas la structure la plus stable correspond à celle qui présente le minimum de déformations structurales du cycle graphitique.
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Stuible, Shirley L. "The efficiency of the B.C. apple marketing system : a structure, conduct and performance evaluation." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/28404.
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The cooperative structure of the B.C. apple marketing system has been in danger of collapse several times over its 70 year history. The most recent upheaval occurred in the early 1980s, when accusations of cost inefficiencies led to several changes in the system. The objective of this study is to provide a structure, conduct and performance evaluation of efficiency of the apple marketing system. This will entail an historical review, a description of the apple industry and an evaluation of its performance with respect to cost efficiency and revenue maximization using the Washington State apple industry as the benchmark.
Apple production in Washington State is about ten times production in B.C., and their typical orchard is about 40 acres versus about 14 acres in B.C. The average Washington packinghouse organization serves about 30 growers to B.C.'s 300, yet their average volume is about 40% larger than the average B.C. packinghouse. Approximately one half of all the Washington packinghouses are cooperatives, whereas nearly all the B.C. packinghouses are cooperatives. Also, the B.C. growers collectively own the central marketing agency and a major processor. The Washington State packinghouses tend to market their own fruit.
The performance of the apple marketing industry is evaluated in terms of revenues, costs and return to growers. The data available from Washington State precludes direct comparisons of prices (and hence revenues). Total and average costs curves are derived for both the packing and marketing functions in the B.C. industry, and these all exhibit the expected shapes. Variable and fixed costs are also broken out and examined, although it appears the fixed cost data includes some variable costs. But the most interesting finding occurs when B.C. and Washington State per unit costs are compared - it appears the postulated size advantages for Washington State do not exist on average, since B.C. costs are lower. Roughly speaking, it costs about $5/box to pack a box in B.C. versus about $6/box in Washington. Marketing costs in both regions are under $1/box.
Returns to the grower, however, are about $3/box in B.C. versus about $5/box in Washington State. This suggests that price or revenue obtained in B.C. is much lower. This could be due to two diferent factors. First, the marketers in B.C. may be too volume oriented at the expense of obtaining the maximum price possible. This study makes no attempt to test this possibility.
The second reason for B.C.'s lower prices is that the average B.C. product is deemed inferior to Washington State apples. Sensitivity tests are performed to evaluate the effect on grower returns of improving the average apple. When Washington State's average apple quality is imposed on the B.C. cost and price structure, grower returns increase by 63% and 9% for the two years tested. This suggests that if B.C. could match the Washington State performance, its growers would benefit significantly. When the B.C. product mix is varied to include ten percent more long storage fruit, less small sized fruit, and more high grade fruit, the grower returns increase by under 1%, 5 to 12%, and 2 to 3%, respectively. In other words, improving the fruit size of B.C. apples appears to be the most effective means of improving grower returns in B.C.Land and Food Systems, Faculty of
Graduate
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Li, Yue. "Investigating Selected Mechanisms of Modulation of BECN1-mediated Autophagy." Diss., North Dakota State University, 2019. https://hdl.handle.net/10365/29775.
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Autophagy is a lysosomal degradation pathway wherein cytoplasmic components not needed by or harmful to the cell are degraded and recycled. BECN homologs are key autophagy proteins consisting of an intrinsically disordered region (IDR), flexible helical domain (FHD), coiled-coil domain (CCD) and β-α repeated, autophagy-specific domain (BARAD). Diverse proteins modulate autophagy by binding BECN1. Understanding the mechanisms by which these proteins regulate BECN1-mediated autophagy is important for developing therapeutics targeting these proteins. Toward this goal, we have developed purification protocols for multi-domain BECN1 fragments to explore the conformational flexibility and interactions. We show that a BECN1 helix transitions between mutually exclusive packing states, wherein it either forms part of the CCD homodimer or packs against the BARAD, but predominantly packs against the BARAD. The same set of residues on this helix contribute to the CCD homodimer or packing with the BARAD, and mutation of these residues abrogates starvation-induced up-regulation of autophagy. Next, we show the equatorial groove of GAPR-1 may be responsible for binding BECN1. The five conserved residues lining the GAPR-1 equatorial groove are essential for the interaction, as mutation of these residues disrupts GAPR-1:BECN1 interaction. We also solved the structure of this pentad mutant, which indicates the changes in the equatorial groove and the improved dimerization of pentad mutant likely abrogates BECN1-binding. We then show that BH3D is not required for BECN1 to up-regulate autophagy, though it is required for binding BCL2 homologs. Therefore, we investigated the interactions between BH3D-containing BECN1 fragments and the BCL2 homolog, M11. BECN1 regions outside the BH3D increase binding to M11 by 5-10 fold. In addition, M11-binding increases flexibility of the nuclear export sequence (NES). Further, homodimerization and thermostability of BECN1 BH3D-FHD-CCD increases upon M11-binding. Lastly, the M11:BH3D-FHD-CCD complex appears to fluctuate between two major types of conformations, which may be mediated by the increased flexibility of BECN1 NES upon binding M11. Lastly, we investigated the interactions between BH3D-containing BECN1 fragments and Bcl-XL. Our results indicate that BECN1 regions outside the BH3D do not affect BECN1 interaction with Bcl-XL. Together, these studies are important for better understanding how proteins down-regulate BECN1-mediate autophagy.NIH: RO3 NS090939, R15 GM122035, P20 RR015566, and R21 AI078198 (S.S). R15 GM113227, P30 GM103332-01, P41 GM103622, and P41 GM103403.; NSF: MCB-1413525 (S.S.); ND Dept. of Commerce: Award #14-11-J1-73 (S.S.)
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Delmas, Carole. "Analyse structurale comparative des lipoarabinomannanes de quatre souches de Mycobacterium bovis BCG." Toulouse 3, 1997. http://www.theses.fr/1997TOU30134.
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Depuis les annees 20, mycobacterium bovis bcg (bacille calmette-guerin) est le vaccin vivant utilise pour la protection antituberculeuse. Pourtant, l'existence d'une variabilite, de 0 a 80%, de la protection antituberculeuse induite par ce vaccin demontre clairement une derive des souches de bcg actuellement utilisees. Un composant majeur des parois mycobacteriennes, le lipoarabinomannane ou lam est suppose, aujourd'hui, etre un facteur determinant dans l'infection et la survie intramacrophagique des mycobacteries, etapes necessaire a la mise en place d'une immunite protectrice par le bcg. L'objectif de ce travail a donc consiste en une analyse comparative de quatre souches de bcg (pasteur, copenhague, glaxo et tokyo), chacune dotee d'un pouvoir vaccinant variable. Cette etude est centree sur l'analyse structurale des lams produits par ces souches vaccinales. Dans un premier temps, nous avons tente d'ameliorer la strategie de purification du lam, travail qui nous a conduits a la caracterisation de deux sous-populations de lams par souche. Tous ces composes se sont averes appartenir a la famille des lams mannosyles ou manlams. Dans un second temps, une etude rmn bidimensionnelle homo- (cosy, hohaha) et heteronucleaire (hmqc, hmbc) nous a permis, pour la premiere fois, de localiser, avec precision, des residus de succinates sur la molecule. Une approche semi-quantitative par l'analyse des spectres 1d (#1h) a egalement ete menees sur ces manlams. Enfin, afin d'evaluer le degre de mannosylation des differents manlams. , nous nous sommes interesses a la mise au point d'une strategie utilisant la chromatographie echangeuse d'anions a haut ph (hpaec) et la fab -ms. Les resultats peu probants obtenus nous ont conduit a nous orienter vers l'electrophorese capillaire qui, dans un premier temps, nous a permis d'acceder a l'aspect qualitatif de la mannosylation des lams. Nous nous sommes ensuite focalises sur l'elaboration d'une strategie en vue d'aborder, a l'aide de cette technique, l'aspect quantitatif de cette analyse.
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Delestrade, Anne. "Stratégie de recherche de nourriture en groupe chez le chocard à bec jaune : Qualité des ressosurces et structure sociale." Paris 11, 1993. http://www.theses.fr/1993PA112386.
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Les relations entre la qualité des ressosurces au sens large (abondance, distribution et qualité au sens strict) et la structure sociale ont été étudiées chez le chocard à bec jaune (Pyrrhocorax graculus) entre 1988 et 1993. Cette étude avait pour but de déterminer l'impact de la structure sociale d'une espèce sur ces capacités d'adaptation à l'excploitation d'un nouveau type de ressources. Le chocard, espèce de Corvidé de montagne très peu étudiée, utilise les ressosurces alimentaires laissées par l'homme en altitude. L'impact de l'utilisation de ce type de ressources (concentrées dans l'espcae et disponible temporairement) sur les paramètres bio-démographiques et comportementaux (recherche de nourriture) ont été analysés grâce à une étude comparative entre différentes populations (liées ou non aux activités humaines) et une étude expérimentale contrôlant la distribution et l'abondance des ressources. Les paramètres de la reproduction (phénologie, succès reproducteur et structure des populations) des chocards en Haute-Savoie (Alpes) utilisant les ressources d'origine humaine ne montrent pas de différences avec ceux obtenus par une population non liée aux activités humaines (Hauts plateaux Sud du Vercors). Par contre, la distribution des groupes en Haute-Savoie est affectée par les fluctuations saisonnières de la distribution et de l'abondance des ressosurces humaines. La strsucture sociale du chocard basée sur des liens sociaux permanents entre les partenaires du couple, mais aussi entre les membres du groupe, ne semble pas permetrre une exploittation optimale de ce type de ressources concentrées.
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Sallares, Jorma Robert. "Towards a new approach to ancient history : the interaction of biological phenomena, social structure and the economy in ancient Attica." Thesis, University of Cambridge, 1986. https://www.repository.cam.ac.uk/handle/1810/250893.
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MacRobbie, Paul Alexander Carleton University Dissertation Geology. "Stratigraphy, structure and volcanogenic sulphides, in Sicker group volcanic rocks on Mt. Sicker, Vancouver Island, B.C." Ottawa, 1988.
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Harrap, Robin Michael Carleton University Dissertation Geology. "Stratigraphy and structure of the Monashee Terrane in the Mount English area, west of Revelstoke, B.C." Ottawa, 1990.
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Frost, Ann C. "Bargaining structure in a decade of environmental change : the case of the B.C. forest products industry." Thesis, University of British Columbia, 1989. http://hdl.handle.net/2429/28710.
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The forest products industry is a major part of British Columbia's economy, employing directly or indirectly about twenty percent of the province's workforce; and accounting for a significant percentage of the province's exports and government revenues. Historically, the industry has been characterized by highly centralized bargaining structures and formal pattern bargaining between the two regions, the Interior and the Coast, and between the two main industry sectors, pulp and paper and solid wood. Recent environmental changes however, have put considerable pressure on the current system. Because of these changes employers now desire less centralized structures and more local control over terms of the collective agreement.
Pressures for decentralization have resulted from a combination of world wide trends and industry specific changes. The globalization of markets, increased volatility of currency exchange rates, and the increasing rate of technological change are examples of the former. Industry specific changes include the diversification of products and markets between regions and firms, and two major labour disputes in the 1980s.
These changes however, have had little effect upon bargaining in the forest products industry. Some changes have occurred, but to date they have not been significant. Employers in the province's pulp and paper sector deaccredited
their employer bargaining association in March 1985. Despite this change, bargaining in the last two rounds has been done jointly, as it has been done for the past four decades. The second change noted is the severing of ties between the Pulp Bureau and FIR, the Coastal solid wood employer association. Previously overseen by a common Chairman, these two bodies are now run independently to encourage the separation of bargaining outcomes in the two sectors. The final change of note is the role reversal between the pulp unions and the IWA. For many years it was the IWA who negotiated what would become the industry wide settlement. In the last two rounds of negotiations, however, the pulp unions have settled first.
Despite what appear to be significant environmental changes, there has been relatively little change in bargaining in this industry. Clearly there are forces in the industry's industrial relations system that are preserving the status quo. Several organizational forces and one environmental force are identified which are preventing change in industry bargaining structures. Organizational forces include third party pressures (specifically threats of government intervention), industry tradition and past practice, and the unions' ability to resist unilateral changes in bargaining. The environmental force preventing employers from forcing change in industry bargaining structure is the economic health of product markets in the two sectors. Not until the pressures for change are great enough to overcome these inertial organizational forces will significant change occur
in the bargaining structure and patterns of the B.C. forest products industry.Business, Sauder School of
Graduate
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Kendrick, Samantha Lynn. "Characterization and Molecular Targeting of the Bcl-2 i-Motif for Modulation of Gene Expression and Induction of Chemosensitivity in Lymphoma." Diss., The University of Arizona, 2010. http://hdl.handle.net/10150/193638.
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The nature of DNA has captivated scientists for more than fifty years. The discovery of the double-helix model of DNA by Watson and Crick in 1953 not only established the primary structure of DNA, but also provided the mechanism behind DNA function. Since then, the demonstration of DNA secondary structure formation has allowed for the proposal that the dynamics of DNA itself can function to modulate transcription. We demonstrate for the first time the i-motif DNA secondary structure formed from an element within the Bcl-2 promoter region has potential to serve as a cellular molecular target for modulation of gene expression. Unlike typical oncogenes, Bcl-2 acts by promoting cellular survival rather than increasing cellular proliferation. The over-expression of Bcl-2, most notably in lymphomas, has been associated with the development of chemoresistance.Transcriptional regulation of Bcl-2 is highly complex and a guanine- and cytosine-rich (GC-rich) region directly upstream of the P1 site has been shown to be integral to Bcl-2 promoter activity. We have demonstrated that the C-rich strand is capable of forming an intramolecular i-motif DNA secondary structure with a transition pH of 6.6 and a predominant 8:5:7 loop using mutational studies coupled with circular dichroic spectra and thermal stability analyses. In addition, a novel assay involving the sequential incorporation of a fluorescent thymine analog at each thymine position provided evidence of a capping structure within the top loop region of the i-motif. Two different classes of steroids either stabilize or destabilize the i-motif structure and this differential interaction results in the activation or repression of Bcl-2 expression. The i-motif stabilizing steroid significantly up-regulated Bcl-2 gene and protein expression in BJAB Burkitt's lymphoma cells while the destabilizing steroid down-regulated Bcl-2 expression in B95.8 Burkitt's and Granta-519 mantle cell lymphoma cells, as well as in a SCID mouse lymphoma model. More importantly, the down-regulation of Bcl-2 led to chemosensitization of etoposide-resistant lymphoma cells demonstrating that Bcl-2 i-motif interactive small molecules can act as chemosensitizing agents. Conversely, compounds that up-regulate Bcl-2 by stabilization of the i-motif have potential for use as neuroprotective agents.
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Ray, Reena. "Structure-function analysis of a mitochondrial cell death protein, Bcl-2/E1B 19K interacting protein 3 (BNip3)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0020/NQ53074.pdf.
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Case, Simon. "Moessbauer spectroscopic and structural studies of magnetic multilayers." Thesis, University of Liverpool, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343621.
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Dexheimer, Thomas Steven. "Defining the Role of DNA Secondary Structures and Transcriptional Factors in the Control of c-myc and bcl-2 Expression." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/195655.
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In this dissertation, we explore the transcriptional regulatory roles of Gquadruplex- forming motifs and the involvement of specific transcriptional factors, which interact with the same elements, in the control of human c-myc and bcl-2 gene expression. The G-quadruplex structures within the NHE III1 region of the c-myc promoter and their ability to repress transcription has been well established. However, a longstanding unanswered question is how these stable DNA secondary structures are transformed to activate c-myc transcription. NDPK-B has been recognized as an activator of c-myc transcription via interactions with NHE III1 region of the c-myc gene promoter. Through the use of RNAi, we confirmed the transcriptional regulatory role of NDPK-B. We demonstrate that NDPK-B has DNA binding activity and the nuclease activity results from a contaminating protein. NDPK-B preferentially binds to the singlestranded guanine-rich strand of the c-myc NHE III₁. Potassium ions and G-quadruplexinteractive agents, which stabilize G-quadruplex structures, had an inhibitory effect on NDPK-B DNA binding activity. Based on our studies, we have proposed a stepwise trapping-out of the NHE III1 region in a single-stranded form, thus allowing singlestranded transcription factors to bind and activate c-myc transcription. This model provides a rationale for how the stabilization of G-quadruplexes within the c-myc gene promoter region can inhibit NDPK-B from activating c-myc transcription. Similarly, the human bcl-2 gene contains a GC-rich region within its promoter region, which is critical in the regulation of bcl-2 expression. We demonstrate that the guanine rich strand within this region can form three intramolecular G-quadruplex structures. Based on NMR studies, the central G-quadruplex forms a mixed parallel/antiparallel structure with three tetrads connected by loops of one, seven, and three bases. The Gquadruplex structures in the bcl-2 promoter extends beyond the ability to form any one of three separate G-quadruplexes to each having the capacity to form either three or six different loop isomers. This suggests that targeting these individual structures could lead to different biological outcomes. We also found that Telomestatin upregulates bcl-2 gene expression, which we propose is a result of inhibiting the binding of the WT1 repressor protein by the formation of a drug-stabilized G-quadruplex structure.
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Schmid, Hans Peter Emil. "Spatial scales of sensible heat flux variability : representativeness of flux measurements and surface layer structure over suburban terrain." Thesis, University of British Columbia, 1988. http://hdl.handle.net/2429/29385.
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The surface character of a suburban area is far from the uniform, smooth and flat planes over which current surface-layer theory is valid and where vertical eddy-fluxes can be assumed to be almost constant horizontally and vertically. The complexity of the surface introduces considerable variability into the atmosphere at small spatial scales. This variability is partly reduced and spatially-averaged by turbulent mixing but still leaves the concerns about the spatial representativeness of sensible heat flux measurements over a suburban area.
The spatial scales of sensible heat flux variability are discussed in terms of the distribution of surface temperature and roughness elements. It is shown that :
(1) an eddy-correlation measurement can be considered spatially representative, if its surface zone of influence (source area) is large enough to include a spatially representative sample of surface temperature and roughness elements.
(2) a quantitative measure of spatial representativeness can be estimated by use of the two-dimensional Fourier transform of the surface temperature and roughness element distributions (i.e. by the normalized integrated variance spectrum).
(3) the source area of an eddy correlation measurement may be evaluated by a numerical model based on a probability density function plume diffusion model. The source area model developed herein can also be used to estimate the relative influence of specific surface sources or sinks upon an eddy-flux measurement in the surface layer.
These concepts are tested in a suburban residential area in Vancouver, B.C., Canada. Remotely sensed surface temperatures and a digitized roughness element inventory are used as data-bases for the Fourier transforms to develop representativeness criteria for eddy-flux measurements. A set of sensible heat flux measurements at six sites and the corresponding source area calculations are used to formulate recommendations for the objective evaluation of the spatial representativeness of sensible heat flux measurements over a suburban area. The validity of the suggested evaluation methods is confirmed by the observations.
Internal boundary layer growth, estimated by the source area model, compares well with existing work. Some consequences of complex surfaces on the surface layer structure are briefly discussed.Arts, Faculty of
Geography, Department of
Graduate
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Delannoy, Clément. "Etude structurale des modifications de la glycosylation des macrophages induites par Mycobacterium bovis BCG." Thesis, Lille 1, 2017. http://www.theses.fr/2017LIL10155/document.
Full textAbstract:
Les macrophages sont des cellules du système immunitaire inné qui régulent la réponse inflammatoire, tout en contribuant à la mise en place de l’immunité adaptative. La glycosylation de la membrane cellulaire est impliquée dans les différents processus physiopathologiques, tels que la défense de l’hôte ou la réponse inflammatoire. Suite à l’exposition à un pathogène, la machinerie de glycosylation peut être perturbée par cet environnement inflammatoire. Des études transcriptomiques ont démontré que l’infection de macrophages humains par des mycobactéries module l’expression de gènes impliqués dans les processus de glycosylation. L’hypothèse qui en découle est que, lors d’une infection mycobactérienne, la glycosylation des macrophages est régulée soit par l'environnement cellulaire soit par le pathogène. L’objectif de notre étude est de déterminer les modifications structurales de la glycosylation suite à une infection mycobactérienne. Pour ce faire, les macrophages issus de la lignée THP-1 et de monocytes sanguins humains sont infectés par Mycobacterium bovis BCG. Les glycannes libérés des macrophages sont analysés par spectrométrie de masse MALDI-TOF. À la suite de l'infection par M. Bovis BCG, les macrophages présentent des différences de N-glycosylation. L'analyse des résultats obtenus montre une modification de la ramification et une augmentation des niveaux de fucosylation des N-glycannes de type complexe. Ces différences de fucosylation sont confirmées par l’utilisation en cytométrie en flux de lectines végétales fluorescentes. L’ensemble de ces résultats nous indiquent que la glycosylation des cellules hôte subit un remodelage suite à l’infection mycobactérienneMacrophages mediate innate immune system through the initiation and regulation of inflammation and contribute to adaptive immunity via antigen processing. Cell surface glycosylation has been widely described to be involved in different physiological or pathological processes, such as host defense, immunological and inflammatory responses. Following pathogens infection, glycosylation machinery can be also disturbed by the cellular environnement. In recent years, several studies have been shown that infection or stimulation of human macrophages with mycobacteria could modulate gene expression related to glycometabolism. These data establish that during mycobacterial infection, glycosylation of macrophages is finely regulated by the cellular environment or by the pathogen. The purpose of our study is to determining the structural modifcations of glycosylation after mycobacterial infection.To accomplish this, macrophages derived from THP-1 and from PBMC were infected with mycobacterium bovis BCG. Once the macrophages are infected, glycans were released by chemical extraction and enzymatic digestion. After purifcation, differents glycans were analyzed by MALDI-TOF spectrometry. To correlate our results, we have also performed FACS analysis using plant lectins. Following M. bovis BCG infection, macrophages present different pattern of N-glycosylation. Analysis of data obtained by mass spectrometry shows antennarisation modification of complex type N-glycans and variations of fucosylation level
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Poulin, Lucie. "Étude de la relation structure-fonction de la protéine BI-1 chez Saccharomyces cerevisiae." Thesis, Université Laval, 2005. http://www.theses.ulaval.ca/2005/23101/23101.pdf.
Full textAbstract:
La mort cellulaire programmée est un processus par lequel les cellules participent activement à leur propre mort. Ce mécanisme est très important au niveau du développement et de la survie de tous les organismes et est régulé par une panoplie de protéines. Parmi les protéines régulatrices figurent la protéine «Bax Inhibitor-1» que l’on retrouve autant chez les cellules animales que végétales. Cette protéine est surtout connue et identifiée par son effet inhibiteur de l’action de la protéine Bax, protéine principalement retrouvée dans les cellules animales qui, lorsque surexprimée, active la mort cellulaire. L’analyse des séquences d’acides aminés de BI-1 provenant de cinq différentes espèces de plantes suggère l’existence de sept domaines transmembranaires avec la présence de résidus chargés dans certains domaines ce qui laisse supposer des interactions avec d’autres molécules. D’un autre côté, le haut niveau de conservation de l’extrémité C-terminale à travers l’évolution dénote son importance fonctionnelle potentielle. Suite à ces constatations, l’étude de la relation entre la structure et la fonction de la protéine BI-1 a été entreprise afin d’identifier des sites potentiellement importants dans la séquence de la protéine BI-1 qui lui permet de contrer l’action de Bax. Nous avons démontré, par délétion graduelle de l’extrémité C-terminale, que cette région est importante pour la fonction de BI-1. Cette extrémité délètée, d’aussi peu que quatre acides aminés, modifie la fonction de la protéine et une délétion de onze acides aminés abolit complètement son effet cytoprotecteur. Nous avons aussi établi, par mutagenèse dirigée, que deux acides aminés chargés sur quatre dans le septième domaine transmembranaire sont importants pour la fonction de BI-1. Finalement, nous avons proposé, suite à l’étude par mutagenèse aléatoire, l’importance possible du cinquième domaine transmembranaire dans la fonction de la protéine BI-1. Nous pouvons donc conclure que la capacité de BI-1 à inhiber l’effet létal de Bax dépend de sa structure.
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Numberger, Siegfried. "New methods of scenario analysis and their application to detecting future structures of B2C E-commerce /." [S.l.] : [s.n.], 2006. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000254889.
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Nogaret, Sophie. "Etude par RMN de macromolécules biologiques : étude structurale de la protéine CGC-19 impliquée dans la biosynthèse d’un métabolite secondaire, la congocidine chez Streptomyces Ambofaciens. Développement d’inhibiteurs des Bcl-2, protéines modulatrices de l’apoptose." Thesis, Paris 11, 2011. http://www.theses.fr/2011PA114848.
Full textAbstract:
Ma thèse comporte deux volets: d’une part, le développement de ligands ciblant les protéines antiapoptotiques et d’autre part, l’étude par RMN des protéines CGC impliquées dans la biosynthèse de la congocidine, métabolite secondaire chez Streptomyces.La famille de protéines Bcl-2 est impliquée dans un des processus clé de la mort cellulaire programmée, appelée l’apoptose mitochondriale. Elle se divise en membres anti-apoptotiques (Bcl-2, Bcl-xL, Mcl-1) et pro-apoptotiques (Bak, Bax et les «BH3»).Ces molécules vont réguler l’apoptose en maintenant ou non l’intégrité de la membrane mitochondriale. En réponse à un signal de stress, les «BH3» neutralisent les antiapoptotiques et activent les pro-morts, leur permettant de former des pores sur la membrane mitochondriale. Ce phénomène aboutit au relargage du cytochrome c dans le cytosol et à l’activation de la cascade des caspases dont la finalité est la destruction de la celluleLa pertinence de l’étude des Bcl-2 s’observe de manière croissante depuis les années 1990. En effet, une surexpression des membres pro-survie de cette famille (Bcl-2, Bcl-xL, Mcl-1, BFL1 etc...) a été observée dans de nombreux cancers. Suite à ce constat, cibler ces molécules est devenue une piste prometteuse en cancérologie par le développement d’inhibiteurs des protéines pro-survie, l’objectif étant de restaurer l’apoptose dans les cellules tumorales.Dans cette perspective, différentes stratégies thérapeutiques ont été imaginées:(i) la thérapie génique avec l’Oblimersen, un ADN antisens développé par Genta, qui inhibe l’expression de la Bcl-2. Néanmoins, les résultats précliniques sont décevants.(ii) l’utilisation de peptides (ou peptidomimétiques) imitant les sentinelles «BH3» comme antagonistes de l’interaction Bcl-xL/Bak. Il faut souligner le concept des «stappled peptides», permettant la stabilisation des hélices par cyclisation des chaînes latérales. Si certaines de ces molécules synthétisées semblent très actives, aucune n’est encore en étude clinique.(iii) le développement de petites molécules non peptidiques, issues d’un criblage systématique in vitro ou in silico et se caractérisant par une grande variété structurale. Parmi ces molécules, certaines sont synthétiques comme l’ABT-737 et l’ABT-263 élaborés par les laboratoires Abbott, grâce à la méthode d’assemblage des fragments (fragment-based drug design) aidée par des études SAR by NMR (structure activity relationship). D’autres sont issues de produits naturels comme le (R)-Gossypol, le TW-37, la sanguinarine ou l’Obatoclax. En 2008, 11 composés étaient en phase préclinique ou clinique et les résultats pour certains d’entres eux semblaient plus prometteurs que pour l’Oblimersen.Ces stratégies ont permis de mettre au point un certain nombre de composés ciblant les protéines anti-apoptototiques. Si certains de ces composés sont actuellement en phase de tests cliniques, les plus prometteurs (ABT) ont démontré une efficacité uniquement vers certains des protéines anti-apoptotiques laissant place à un phénomène d’échappement des cellules cancéreuses.Un criblage réalisé à l’ICSN par l’équipe de F. Guéritte (Pôle Substances Naturelles Plantes) a permis d’identifier une nouvelle classe de molécules ayant une affinité de l’ordre du μM pour Bcl-xL. Parmi ces composés, deux présentent une attractivité d’un point de vue structural qui rend faisable leur synthèse chimique:(i) la meiogynine A, un sesquiterpène dimère de structure originale isolé des écorces de Meiogyne cylindrocarpa, une plante de Malaisie.(ii) le drimane, un sesquiterpène isolé en grandes quantités du genre zygogynum, une espècede Nouvelle-Calédonie.Ainsi, des collaborations ont été établies au sein de l’ICSN, réunissant diverses expertises (chimie, biologie, physicochimie et modélisation) afin de dégager les synergies souhaitables.Dans la perspective de la conception rationnelle d’analogues aux propriétés améliorées ciblant l’ensemble des membres anti-apoptotiques de la famille Bcl-2, ma contribution est de choisir les cibles biologiques (Bcl-xL et Mcl-1), de les obtenir pures et marquées en isotopes stables afin de réaliser par RMN et modélisation moléculaire une étude structurale des complexes protéines/ligands et de définir un modèle d’interaction.Le deuxième volet de ma thèse, à dominante fondamentale, a pour objectif de caractériser par RMN les médiateurs enzymatiques d’une voie de biosynthèse d’un métabolite secondaire, la congocidine issue des bactéries Streptomyces Ambofaciens.La congocidine présente des propriétés antivirales et anticancéreuses de par sa capacité à se fixer à l’ADN. Cependant, du fait de sa forte toxicité, cette molécule ne peut pas être utilisée directement à des fins thérapeutiques.L’analyse des groupes de gènes impliqués dans la biosynthèse de la congocidine a mis en évidence 24 gènes. Seuls certains intermédiaires réactionnels ont été identifiés. Cependant, le rôle précis des produits de ces gènes n’est pas encore bien défini.Ainsi, en collaboration avec l’équipe de JL Pernodet à l’Université d’Orsay, nous nous sommes intéressés à deux enzymes en particulier intervenant dans la synthèse de la congocidine, les protéines CGC-10 et CGC-19.L’objectif de cette collaboration est d’utiliser la spectroscopie RMN couplée à la modélisation moléculaire sous contraintes expérimentales afin de déterminer la structure de ces deux protéines. Nous souhaitons apporter des informations sur l’éventuelle présence de motifs structuraux au sein de ces protéines afin de mieux comprendre leur fonction et de définir à quel moment de la voie de biosynthèse elles interviennent.Concernant la protéine CGC-10, nous avons conçu un plasmide optimisé que nous avons fait synthétiser. Le gène obtenu a été cloné dans un vecteur d’expression choisi par nos collaborateurs (pQE30).Concernant la protéine CGC-19, nous allons en décrire les étapes d’expression et de purification qui nous ont permis d’enregistrer l’ensemble des expériences 3D-triple résonnance nécessaires à la détermination de la structure de la protéine. De plus, il a été mis en évidence la présence d’une modification post-traductionnelle de type phosphopanthéténylation au sein de cette protéine. Nous avons produit l’enzyme responsable de cette modification, la sfp, afin de pouvoir effectuer la réaction et suivre l’effet de la modification sur les spectres RMN de la protéine et donc sur la structure.Ce projet, qui s’inscrit dans une perspective de recherche à plus long terme, a pour objectif de caractériser précisément le mécanisme de production de la congocidine. A travers cette démarche, il s’agit de combiner la biologie moléculaire (modification en amont les gènes) à la chimie afin d’obtenir des molécules différentes aux propriétés améliorées et non toxiquesMy PhD thesis contains two parts: development of ligands against anti-apoptotic proteins and structural study of CGC proteins involved in the biosynthesis of congocidine, a Streptomyces Ambofaciens secondary metabolite.The first project concerns the NMR study of the interactions between the anti-apoptotic proteins and two potential ligand candidates, the Meiogynine and the Drimane. These two terpenoïds, identified from ICSN’s chemical library screening against the Bcl-xL protein, have shown a significant inhibiting activity, thus opening promising perspectives for the treatment of cancer cells overexpressing anti-apoptotic proteins. In fact, as these compounds are considerably smaller than the binding site, our objective is to introduce modifications (such as elongation of their structure, functionalization with hydrophilic groups etc.) that may improve their binding properties as well as their delivery and bioavailability.Following to the successful recombinant expression and purification, necessary to obtain labelled targets (15N/13C), our preliminary NMR studies suggested a rather universal action of our candidates, capable to bind not only to Bcl-xL but also to the other major anti-apoptotic protein, Mcl-1. Titration experiments revealed significant perturbations of the HSQC protein NMR spectra with the progressive disappearance of several protein HN and ligand signals, confirming dissociation constants at the µM region for both targets. However, the intermediate chemical exchange NMR regime observed, associated with the weak ligand solubility, poses severe difficulties for the structural elucidation of the complexes by classical NMR methods.In this work alternative approaches for the localisation of the ligands in the hydrophobic cleft of both target proteins will be presented.Oligopyrroles are secondary metabolites synthesized by Streptomyces bacteria. This family of natural products, composed by one or more pyrrole-2-carboxamide groups is characterized by a variety of biological activities such as antiviral, antitumor and antibiotic functions.One of the best-known metabolites is the congocidine, extensively studied due to its capacity to bind into the minor groove of the DNA double helix, with strong sequence specificity. However, because of its strong toxicity, this molecule cannot be directly used for therapeutic purposes.The analysis of the groups of genes involved in congocidine biosynthesis brought to light 24 genes, but their precise role is not yet well defined. We were particularly interested in two enzymes: the proteins called CGC-10 and CGC-19. For the recombinant expression of the first one, we designed an optimized insert which was cloned in an expression vector pQE30.Concerning CGC-19, the stages of expression and purification, which allowed us to obtain doubly-labeled protein, as well as the 3D NMR experiments for spectral assignment and structure elucidation, will be discussed.Furthermore, we were interested in the holo- state of this protein obtained through a post-traductional modification (phosphopanthéténylation). To this, we produced the enzyme responsible for this modification, Sfp, carry out the reaction in vitro and follow the effect of the modification at the NMR spectra
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Braun, Craig Ronald. "Structural Characterization of BCL-2 Family Protein Interactions Using Photoreactive Stapled Peptides and Mass Spectrometry." Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10139.
Full textAbstract:
Recent improvements in mass spectrometry instrumentation have stimulated the fusion of this technology with protein crosslinking to advance the structural proteomics field. However, analysis of complex datasets from crosslinking experiments remains a bottleneck. The majority of crosslinking studies for structural characterization of protein- protein interactions have been conducted with reagents specific for discrete amino acids. While this approach simplifies data analysis, the requirement for specific functionalities to be present at the interaction interface limits resolution. Herein, we report the application of stapled peptides for the development of photoaffinity reagents for mass spectrometric characterization of BCL-2 family protein interactions. To validate this approach, we synthesized photoreactive stabilized alpha-helices of BH3 domains (pSAHBs) incorporating a benzophenone containing amino acid, and demonstrated that the photo crosslinking specificity of these reagents paralleled the interaction specificity of the native proteins. We show that the standard SEQUEST algorithm is effective at identifying specific amino acids crosslinked by pSAHBs, and that this information can be used to create distance restraints for characterizing interaction interfaces by in silico docking. The pSAHB approach is applied to characterize previously elusive activating interactions between BH3 domains and the proapoptotic proteins BAX and BAK. We demonstrate that full-length BAK requires a direct activation stimulus, and that this involves interaction at a canonical surface groove at the C-terminal face of BAK. We confirmed that initiation of direct BAX activation occurs at a geographically distinct site at the N-terminal face of BAX, but further find that induced release of its C-terminus from the canonical groove exposes these residues for secondary BH3 interaction. These data suggest that BAX may be subject to a two-step activation mechanism within distinct cytosolic and mitochondrial compartments. Finally, we report the structural characterization of an interaction between BAD and glucokinase, the first description of a BH3 domain interaction with a non-BCL-2 family member. We identify the active site region of glucokinase as the BAD interaction site, establishing this region as a novel target for development of glucokinase activators. We conclude that the pSAHB approach represents a rapid and powerful approach to protein interaction site identification that complements conventional structural biology techniques.
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Leonard, Richard. "Variable structural style, stratigraphy, total strain and metamorphism adjacent to the Purcell thrust, near Blackman Creek, B.C." Thesis, McGill University, 1985. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=63282.
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Su, Minfei. "Structural Studies of the Mechanism by Which BCL-2 and Beclin Proteins Regulate Autophagy and Apoptosis." Diss., North Dakota State University, 2016. https://hdl.handle.net/10365/27994.
Full textAbstract:
Autophagy and apoptosis are catabolic pathways essential for homeostasis in all eukaryotes. While autophagy usually promotes cell-survival by enabling degradation and recycling of damaged macromolecules, apoptosis is the canonical programmed cell death pathway. Dysfunction of autophagy and apoptosis is implicated in diseases like cancers, cardiac disease, and infectious disease. Beclin homologs are key for autophagy as they are core components of class III phosphatidylinositol 3-kinase autophagosome nucleation and maturation complexes. Anti-apoptotic Bcl-2s inhibit apoptosis through binding and antagonizing pro-apoptotic Bcl-2s. Anti-apoptotic Bcl-2s also down-regulate autophagy by binding to the Bcl-2 homology domain 3 (BH3D) of Beclin homologs, thereby enabling crosstalk between apoptosis and autophagy. The central goal of my doctoral research is to understand the structure-based mechanism of selected Bcl-2s and Beclin homologs in the regulation of autophagy and apoptosis. -Herpesviruses are common human pathogens that encode viral Bcl-2s to facilitate viral reactivation and oncogenic transformation. M11, a viral Bcl-2, and Bcl-XL, a cellular Bcl-2, bind with comparable affinities to the Beclin 1 BH3D. By assessing the impact of different Beclin 1 BH3D mutations on binding to M11 and Bcl-XL, we developed a cell-permeable inhibitory peptide that targets M11, but not Bcl-XL. The mechanism by which this peptide specifically binds to M11 was elucidated by determining the X-ray crystal structure of the peptide:M11 complex. Our attempts to investigate the role of other Bcl-2s in these pathways were unsuccessful. In one project, we were unable to express and purify BALF1, another viral Bcl-2. In another, no interaction was detected between purified samples of the anti-apoptotic Bcl-2 homolog Mcl-1, and the autophagy protein Atg12, that had previously been shown to bind. We also delineated the domain architecture of Beclin 2, a novel Beclin homolog and attempted to express and purify different Beclin 2 constructs for structural studies. We successfully purified and solved the X-ray crystal structure of the Beclin 2 coiled-coil domain (CCD), showing it is a curved, anti-parallel, meta-stable coiled-coil homodimer with seven pairs of non-ideal packing residues. In general, mutating the non-ideal packing residues to leucines enhanced Beclin 2 CCD homodimerization, but also weakened its binding to Atg14 CCD.NIH grant R21 AI078198, NIH grant R03 NS090939, NSF grant MCB 1413525, NSF grant HRD-0811239, and P30 GM103332-01 to Dr. Sangita Sinha, and North Dakota EPSCoR doctoral dissertation award for Minfei Su and Dr. Sangita Sinha
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Culver, James William. "The analysis of dielectric loss in co-planar waveguide structures using generalized transverse resonance." [Tampa, Fla.] : University of South Florida, 2005. http://purl.fcla.edu/fcla/etd/SFE0001036.
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Al, Rifaie Mohammed Jamal. "Resilience and Toughness Behavior of 3D-Printed Polymer Lattice Structures: Testing and Modeling." Wright State University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=wright1502760172343413.
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Drew, Jeffrey John. "A re-evaluation of the seismic structure across the active subduction zone of Western Canada." Thesis, University of British Columbia, 1987. http://hdl.handle.net/2429/26248.
Full textAbstract:
The 1980 Vancouver Island Seismic Project (VISP) was conducted to investigate lithospheric structure associated with the underthrusting oceanic Juan de Fuca plate and the overriding continental America plate. The principal components of the survey were: (l) an onshore-offshore refraction line, which was approximately perpendicular to the continental margin (line 1), and (2) a refraction line which ran along the length of Vancouver Island approximately parallel with the continental margin (line IV). Lines I and IV were originally interpreted by Spence el a.1. (1985) and McMechan and Spence (1983), respectively. However since the original interpretations of these lines, deep multichannel seismic reflection data have been obtained on southern Vancouver Island as part of the 1984 LITHOPROBE project and off the west coast of the island during a marine survey in 1985.
This study was undertaken to resolve differences between the subsurface structures proposed in the original interpretations of lines I and IV and those suggested by the more recently acquired deep reflection data. The vertical two-way traveltimes to prominent
reflectors, observed in the onshore-offshore deep reflection data, were used as a constraint in constructing velocity models which are consistent with both the reflection and refraction data. The traveltimes and amplitudes observed in the VISP refraction data were modeled using a two-dimensional raytracing and asymptotic ray theory synthetic
seismogram routine.
The principal difference between the model originally interpreted for line I and the revised model involves the introduction of a twice repeated sequence of a low velocity zone (≈ 6.4 km/s) above a thicker high velocity zone (≈ 7.1 km/s) for the underplated region directly above the subducting Juan de Fuca plate in place of the single high velocity block underlain by a thick low velocity zone. The revised model for line IV is significantly different from the originally interpreted model. The two low-high velocity zones of line 1 are continued along the length of the island at depths between 10 and 35 km. Below this, the structure of the subducted plate is included to maintain consistency with the revised model developed for line 1.
Additional features of the revised onshore-offshore model corresponding to line 1 include
an oceanic lithosphere that dips approximately 3° beneath the continental slope, then 14° to 16° beneath the continental shelf and Vancouver Island, and an average velocity for the upper oceanic mantle of 8.22 km/s. Two separate two-dimensional models were needed to explain the data collected along line IV as a result of considerable
azimuthal coverage due to a 30° change in profile direction. The revised models developed for line IV are consistent with the revised model developed for line 1. The velocity in the upper 10 km ranges from 5.5 km/s to approximately 6.7 km/s. Below 10 km the velocity structure is consistent with that interpreted for line 1 and shows some variations along strike of the subduction zone.
Several possible interpretations can be made for the origin of the sequence of layers directly above the subducting plate beneath Vancouver Island. The two favored interpretations
are: (1) a. three stage tectonic process consisting of: stage 1 — offscraping of sediment from the top of the subducting plate forms the uppermost low velocity layer in the sequence; stage 2 — an imbricated package of mafic rocks derived by continuous accretion from the top of the subducting oceanic crust forms the first high velocity layer; and stage 3 — stages 1 and 2 repeat themselves with stage 2 currently occurring; or (2) remnant, pieces of oceanic lithosphere left stranded above the current subducting
plate during two previous episodes of subduction in which the subduction thrust jumped further westward isolating the remnant. The revised model along line IV indicates
that this process of subduction underplating could have been a pervasive feature of this convergent margin.Science, Faculty of
Physics and Astronomy, Department of
Graduate