Dissertations / Theses on the topic 'Ply damage'
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Dimant, Ron A. "Damage mechanics of composite laminates." Thesis, University of Cambridge, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338020.
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Hottengada, Babruvahan. "Investigation of Microcracking and Damage Propagation in Cross-Ply Composite Laminates." ScholarWorks@UNO, 2006. http://scholarworks.uno.edu/td/367.
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The present study investigates microcracking and damage progression in IM7/977-2, IM7/5555, and IM7/5276-1 [0/90/90/0] laminates. For each material system, seven to eight small coupons were axially loaded in a tensile substage. At increments of around 50 MPa the surfaces of the specimens were inspected via optical microscopy so that a history of microcracking damage as a function of applied loading could be charted. In the IM7/977-2 laminates microcracks were found to initiate on average at around 1050MPa; microcracking initiation for the other two systems was around 850 to 900 MPa. Also, the IM7/977-2 system displayed a steeper increase in crack density as a function of applied loading than the other two systems. The IM7/5555 system was the only system that achieved a microcracking saturation density; the saturation density was found to be around 17 cracks per centimeter. While the IM7/977-2 and IM7/5276-1 systems typically broke into two pieces at failure, the IM7/5555 specimens shattered into pieces. In addition, delaminations were observed in a majority of the IM7/5555 specimens at loadings 250MPa under the failure loads.
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Leong, Kok Hoong. "Damage accumulation in cross-ply polymer matrix composite laminates under mechanical loading." Thesis, University of Cambridge, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241115.
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Demerath, Brandon Michael. "Low velocity impact damage assessment in IM7/977-3 cross-ply composites using 3D computed tomography." Thesis, University of Iowa, 2015. https://ir.uiowa.edu/etd/1583.
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Low-velocity impact damage in IM7/977-3 carbon fiber reinforced polymer (CFRP) composites was investigated using 3D computed tomography (CT). 32-ply IM7/977-3 symmetric cross-ply composites were impacted at different impact energy levels and with different impactors (DELRIN® resin flat-ended cylindrical and tool steel hemispherical strikers) using an Instron 8200 Dynatup drop-weight impact machine. The impact energies were chosen to produce slightly visible damage, characterized by short cracks on the impacted surface and little delamination on the non-impacted surface (29.27 J), and barely visible damage, characterized by indentation on the impacted surface but no visible delamination on the back surface of the specimens (20.77 J). Internal damage was assessed using the Zeiss METROTOM 1500 industrial CT scanning system, and CT images were reconstructed using VGStudio MAX and the MyVGL 2.2 viewer. To determine the extent of the damage zone, impacted 152.4 mm square composite plates were initially scanned. As the relatively large specimen size did not allow for evaluation of internal cracks and isolation of delamination at ply interfaces, smaller specimens that enclosed the damaged region (45 mm square plates) were cut out and imaged. The CT scan results showed that volume of the impact damage zone had a generally positive correlation with impact energy, maximum load, and maximum deflection, but that the relationship was generally weak. Absence of a definite correlation between damage volume and impact energy was unexpected, as the difference in the impact energy was up to 30%.
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Bouscarrat, David. "Time-dependent damage in woven-ply thermoplastic composites above glass transition temperature Influence of time-dependent phenomena on translaminar fracture of woven-ply C/PPS laminates above the glass transition temperature." Thesis, Normandie, 2019. http://www.theses.fr/2019NORMIR29.
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Dans les composites associant matrice organique et renfort fibreux, le couplage entre comportements visqueux (viscoélasticité, viscoplasticité) et mécanismes d’endommagement est très peu étudié à l’échelle mésoscopique et se limite principalement à des analyses post-mortem. Pour des applications aéronautiques à haute température (e.g., nacelle de moteur d’avion), la problématique est encore plus complexe. Notamment au sein de stratifiés à matrice thermoplastique haute performance PPS renforcés par des tissus de fibres de carbone. Ces matériaux sont caractérisés par des zones riches en matrice dont les comportements visqueux sont amplifiés pour des températures d’utilisation en service (i.e., 120°C) supérieures à la température de transition vitreuse de la matrice (environ 95°C). La question fondamentale qui se pose alors est de comprendre comment mettre en évidence et quantifier l’endommagement d’origine visqueuse lorsque le comportement de stratifiés C/PPS est piloté par la réponse mécanique de la matrice. Pour apporter des réponses à cette problématique, on peut évaluer : (1) l’influence de la viscosité de la matrice sur le comportement en rupture translaminaire - (2) le visco-endommagement lors de chargements de type fluage-recouvrement. Ces deux axes d’étude reposent notamment sur la mise au point de protocoles expérimentaux adaptés à des essais mécaniques à haute température. Ainsi, l’originalité de ces travaux est de combiner différentes techniques complémentaires (émission acoustique, réplique de bords, analyse fractographique, tomographie) qui permettent une analyse in-situ en temps réel des mécanismes d’endommagement qui coexistent et inter-agissent lors des différentes phases du chargement. En utilisant le protocole mis au point dans des conditions de température supérieure à la Tg du matériau, ces techniques apportent des informations pour quantifier et dissocier les différents comportements matériaux (viscoélasticité, viscoplasticité, endommagements) ainsi que des effets structures (rotation des fibres). Des analyses d’images basées sur des algorithmes de dilatation/érosion implémentées dans Matlab permettent d’évaluer la densité de fissuration (intra- et inter-torons) surfacique à partir des répliques de bords. A l’échelle macroscopique, la réponse thermomécanique du C/PPS est peu influencée par les comportements visqueux du C/PSS que ce soit pour des stratifiés quasi-isotrope (comportement majoritairement piloté par les fibres à 0°) ou à plis orientés (comportement majoritairement piloté par la matrice PPS). Enfin, la rupture translaminaire ductile est caractérisée par l’évolution de l’énergie acoustique cumulée en fonction du taux de restitution d’énergie. L’instabilité de la rupture translaminaire ne permet pas d’évaluer l’influence des effets visqueux sur la ténacité en mode I du matériau à l’initiation. Aux échelles micro- et mésoscopiques, les résultats obtenus montrent clairement le visco-endommagement au sein de stratifiés C/PPS à plis orientés sollicités en fluage à T > Tg. En mettant en œuvre ce protocole, la pertinence/complémentarité démontrées de l’émission acoustique associée à la quantification de la densité de fissuration permettent d’envisager l’étude du couplage entre effets visqueux et endommagement au sein de stratifiés C/PPS soumis à des chargements à haute température. Cette problématique est essentielle du point de vue de la durabilité des structures composites dans un environnement moteurIn fiber-reinforced polymer matrix composite materials, the coupling between viscous behaviour (viscoelasticity, viscoplasticity) and damage mechanisms is very little studied at the mesoscopic scale and is mainly limited to port-mortem analyses. For high-temperature aeronautical applications (e.g., aircraft engine nacelle), the problem is even more complex within high performance thermoplastic matrix laminates PPS (Polyphenylene Sulfide) reinforced with carbon fiber fabrics. Indeed, these materials are characterized by matrix-rich zones whose viscous behaviors are exacerbated for service temperatures (i.e., 120°C) higher than the matrix glass transition temperature (about 95°C). It is therfore necessary to develop specific experimental procedures to highlight and quantify the viscous damage when the behaviour of C/PPS laminates is driven by the mechanical response of the matrix. In order to provide answers to this problem, one can evaluate : (1) the influence of the matrix viscosity on the translaminar fracture behaviour - (2) the time-dependent damage during creep-type loading. These two lines of study are based on the development of experimental protocols adapted to high temperature mechanical testing. Thus, the originality of this work is to combine different complementary techniques (acoustic emission, edge replication, fractographic analysis, tomography) which allow in-situ and in real time analyses of the damage mechanisms that coexist and interact during the different loading phases. Using the protocol developed under conditions of temperature higher than the Tg of the material, these techniques provide information to quantify and dissociate the different material behaviours (viscoelasticity, viscoplasticity, damage) as well as structural effects (fibre rotation). Image analyses based on dilatation/erosion algorithms implemented in Matlab allow the evaluation of the surface cracking density (intra- and inter-strand) from edge replicas. On a macroscopic scale, the thermomechanical response of C/PPS is little influenced by the viscous behaviour of C/PSS, whether for quasi-isotropic laminates (behaviour mainly driven by 0°fibres) or with oriented plies (behaviour mainly driven by the PPS matrix). Finally, the ductile translaminar fracture is characterized by the evolution of the cumulative acoustic energy as a function of the energy restitution rate. The instability of the translaminar fracture does not allow the quantification of the influence of viscous effects on the mode I toughness of the material at initiation. At micro and mesoscopic scales, the results obtained clearly show time-dependent damage within oriented plies C/PPS laminates subjected to creep loadings at T > Tg. By implementing this protocol, the demonstrated relevance/complementarity of the acoustic emission associated with the quantification of the cracking density allows the study of the coupling between viscous effects and damage within C/PPS laminates subjected to high temperature loading. This problem is essential from the point of view of the durability of composite structures in an engine environment
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Orifici, Adrian Cirino, and adrian orifici@student rmit edu au. "Degradation Models for the Collapse Analysis of Composite Aerospace Structures." RMIT University. Aerospace, Mechanical and Manufacturing Engineering, 2007. http://adt.lib.rmit.edu.au/adt/public/adt-VIT20080619.090039.
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García, Rodríguez Santiago. "X-ray tomography investigation of the impact damage mechanisms of thin-ply composites and the use of veils to improve their impact tolerance." Doctoral thesis, Universitat de Girona, 2019. http://hdl.handle.net/10803/668028.
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This thesis investigates the impact response of novel laminates made with “thin-plies” as well as proposes a toughening method to improve their impact tolerance. To this purpose, we devised a wide experimental campaign combined with cutting-edge non-destructive inspection techniques such as nanometric-resolution X-ray micro-computed tomography. Overall, we gave a step forward towards the inclusion of thin-ply laminates in new commercial aircraft designsAquesta tesi investiga la resposta a impacte de laminats compostos fabricats amb "thin-plies" i proposa una tècnica de reforç externa per millorar la seva tolerància al dany (el mètode consisteix a intercalar vels molt fins amb forma de "teranyina" entre les diferents capes del laminat per absorbir més energia durant l'impacte). Per a això, hem dissenyat una extensa campanya experimental acompanyada amb tècniques punteres d'inspecció no destructiva com la tomografia computada de raigs-X. En definitiva, hem fet un pas endavant cap a la inclusió dels laminats "thin-ply" en el disseny de futurs avions
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Lavoie, J. André. "Scaling Effects on Damage Development, Strength, and Stress-Rupture Life on Laminated Composites in Tension." Diss., Virginia Tech, 1997. http://hdl.handle.net/10919/30510.
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The damage development and strength of ply-level scaled carbon/epoxy composite laminates having stacking sequence of [+Tn/-Tn/902n]s where constraint ply angle, T, was 0, 15, 30, 45, 60, and 75 degrees, and size was scaled as n=1,2,3, and 4, is reported in Part I. X-radiography was used to monitor damage developments. First-ply failure stress, and tensile strength were recorded. First-ply failure of the midplane 90 deg. plies depended on the stiffness of constraint plies, and size. All 24 cases were predicted using Zhang's shear-lag model and data generated from cross-ply tests. Laminate strength was controlled by the initiation of a triangular-shaped local delamination of the surface angle plies. This delamination was predicted using O'Brien's strain energy release rate model for delamination of surface angle plies. For each ply angle, the smallest laminate was used to predict delamination (and strength) of the other sizes.
The in-situ tensile strength of the 0 deg. plies within different cross-ply, and quasi-isotropic laminates of varying size and stacking sequence is reported in Part II. No size effect was observed in the strength of 0 deg. plies for those lay-ups having failure confined to the gauge section. Laminates exhibiting a size-strength relationship, had grip region failures for the larger sizes. A statistically significant set of 3-point bend tests of unidirectional beams were used to provide parameters for a Weibull model, to re-examine relationship between ultimate strength of 0 deg. plies and specimen volume. The maximum stress in the 0 deg. plies in bending, and the tensile strength of the 0 deg. plies (from valid tests only) was the same. Weibull theory predicted loss of strength which was not observed in the experiments. An effort to model the durability and life of quasi-isotropic E-glass/913 epoxy composite laminates under steady load and in an acidic environment is reported in Part III. Stress-rupture tests of unidirectional coupons immersed in a weak hydrochloric acid solution was conducted to determine their stress-life response. Creep tests were conducted on unidirectional coupons parallel and transverse to the fibers, and on ±45°. layups to characterize the lamina stress- and time-dependent compliances. These data were used in a composite stress-rupture life model, based on the critical element modeling philosophy of Reifsnider, to predict the life of two ply-level thickness-scaled quasi-isotropic laminates.Ph. D.
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Strauss, Elizabeth Ann. "Finite element analysis of damaged cross-ply composite laminates." Thesis, Virginia Polytechnic Institute and State University, 1987. http://hdl.handle.net/10919/52060.
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The problem of transverse cracks in T300/5208 graphite-epoxy cross-ply laminates was studied using generalized plane strain finite element analysis. The degradation of elastic modulus, Poisson's ratio, shear modulus, and coefficient of thermal expansion was predicted and then compared with analytical models and experimental data. The elastic modulus was predicted to exhibit relatively small degradation as a function of crack density as compared to the Poisson's ratio, shear modulus, and coefficient of thermal expansion which were predicted to have large degradations.
The resulting state of stress was also studied for several crack spacings. Interlaminar stresses were predicted to form as a result of the free surface of the crack. The crack tip also caused all the nonzero stresses to exhibit singular behavior at the crack tip.Master of Science
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Tchír, Michal. "Srovnávací studie únosnosti a tuhosti vybraných spojů kovové a kompozitní části konstrukce." Master's thesis, Vysoké učení technické v Brně. Fakulta strojního inženýrství, 2016. http://www.nusl.cz/ntk/nusl-241680.
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V současnosti jedna z metod spojování zejména tlustých a vysoce zatížených kompozitních komponent je šroubový spoj, který je možné rozebrat pro případ opravy na rozdíl od lepeného spoje. Kompozitní konstrukce se tradičně dimenzují tak, aby během provozu nedošlo k porušení první vrstvy laminátu, nicméně důležité je taky poznat chování laminátu po porušení první vrstvy. Pro strukturální analýzu nejenom spojů, ale také dalších komponent se používá metoda konečných prvků a protože moderní nelineání řešiče jsou schopné modelovat chování laminátu po porušení první vrstvy, tato schopnost jednoho z nich byla využita v této práci při zkoumaní chování sklolaminátu spojeného s hliníkovou částí šrouby. Konečno-prvkové modely dvou spojů kovové a kompozitní části konstrukce schopné popsat progresivní porušování laminátu byly postaveny s využitím tří různých poruchových kritérií – kritéria maximálního napětí, kritéria Hill a kritéria Tsai-Wu. Problém byl řešen s využitím řešiče Nastran. Křivky síla-posuv, tuhost-posuv a hodnoty zatížení při hraničním posuvu byly porov-nány s výsledky experimentů. Jelikož faktor zbytkové tuhosti ovlivňuje výsledky ana-lýzy progresivního porušování, byly provedeny citlivostní studie zkoumajíci vliv faktoru na přesnost a stabilitu výpočtu. Shoda výpočtu s experimentem v případe prvního šroubového spoje je méně uspokojivá, nicméně shoda v případě druhého spoje, který má zesilující tenkou ocelovou destičku na spodní straně, je podstatně lepší. Vý-borná shoda je zejména při použití interaktivních kritérií Hill a Tsai-Wu.
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Roberts, Michael. "Direct cellular effects of poly(adp-ribose) polymerase inhibitors." Thesis, University of Newcastle Upon Tyne, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265487.
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Jones, Dawn L. "The cloning and sequencing of the plant nuclear poly ADP-ribose polymerase gene." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262927.
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The project was to clone the gene encoding a nuclear enzyme poly-ADP-ribose polymerase (PARP) involved in the posttranslational modification of nuclear proteins. This modification is important in the regulation of various cellular processes such as cell differentiation, proliferation and in the molecular events involved in the recovery of cells from DNA damage. At the start of this project this enzyme had been well characterized in animal systems but had not as yet been explored in plants. Firstly, I showed the enzyme to be present in higher plant nuclei, by a series of experiments including enzyme assays and western blotting (probed with a polyclonal antibody specific to the protein). Molecular biology approaches were used to isolate the gene encoding the PARP enzyme. These techniques included screening of cDNA libraries, constructed in λZAPII, with both the polyclonal antibody and a gene probe (a restriction digest of a human PARP gene was performed and a 1.4Kb fragment containing the C-terminal region of the gene used as a probe). This identified a number of bacteriophages from which sequence information was obtained (by making and extracting phagemids). Subsequent translation of these nucleotide sequences revealed that one of the sequences (245941) obtained in this manner showed homology to the PARP protein. Degenerate oligonucleotide primers, designed to the conserved C-terminal region of the gene, were also used in an attempt to amplify a 375bp region of the gene thought to contain the PARP signature. PCR products of the expected size (375bp) were obtained from an SST cDNA library. These PCR products hybridized to the gene probe (mentioned earlier). Subsequent subcloning revealed multiple products of 375bp comigrating in the agarose gels. Two different sequences were obtained which were, upon translation, shown not be PARP-like sequence.
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Nichols, Joseph A. "In vitro binding of base excision repair glycosylases to poly(adp-ribose)." Online access for everyone, 2008. http://www.dissertations.wsu.edu/Thesis/Summer2008/j_nichols_071008.pdf.
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Zhang, Tongjie. "Chemical Recycling of Poly(ethylene terephthalate): Effects of Mechanical Stress and Radiation Damage on Hydrolysis." Digital WPI, 2020. https://digitalcommons.wpi.edu/etd-theses/1376.
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Finding an effective recycling process for oceanic plastic waste is increasingly important to address environmental pollution. Plastic waste is a bountiful and sustainable resource for energy production and chemical recycling. Polyethylene terephthalate (PET), one of the most common commercialized polymers, is promising to be recycled by hydrolysis. The objective of this work was to study the effects of mechanical stress and radiation damage on PET structure and hydrolysis reactivity. Ball-milling and photo-damaging pretreatments were carried out to imitate the environmental degradation in the ocean environment. An evident decrease in crystallinity with increasing ball-milling time was observed. This decrease in crystallinity caused by fractures of chemical bonds induced by photoaging and ball-milling treatments were investigated. PET was hydrolyzed into ethylene glycol (EG) and terephthalic acid (TPA) at 200°C in tube hydrolysis reactors without catalysts. EG and TPA were recovered after PET depolymerization. Thermogravimetric analysis and Fourier-transform infrared spectroscopy indicated that the recovered TPA was purified. Qualitative and quantitative analysis of TPA and EG were performed by using UV-Visible spectrophotometer and High-Performance Liquid Chromatograph (HPLC) separately. At 200 ℃, the conversion rate of fresh and ball-milled PET samples was improved from 16-18% with a one-hour reaction time compared to 87-91% with a two-hour reaction time. This depolymerization behavior supported that the conversion rate of PET was increased with increasing reaction time at the same temperature. The experiment results, however, showed PET conversion, TPA yield, and EG yield did not improve after ball-milling and photo-damaging treatment. After retention time of 1 hour, PET conversions, yields of TPA, yields of EG of various PET samples were 16.5±1.5%, 11.5±1.5% and 0.70 ± 0.20%, respectively. Mechanical treatment and radiation damage did not affect PET reactivity significantly in this experiment. Two main reasons were discussed to explain this result. The effect of radiation damage and mechanical stress was obscured by the more dominant reaction condition, temperature. The pretreatments in this experiment were not strong enough to affect PET reactivity. Based on the current results, recommendations for the hydrolysis temperature, potential catalysts, and more robust pretreatment methods were provided for further outlook of studying environmental effects on PET hydrolysis.
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Sellou, Hafida. "Role of Poly-(ADP-ribose)-ylation signaling pathway in the chromatin remodeling after DNA damage." Thesis, Rennes 1, 2016. http://www.theses.fr/2016REN1B029/document.
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Chaque cellule humaine est constamment soumise à des agressions extérieures comme l'exposition aux rayons Ultra-Violets, agents chimiques, etc. ou endogènes provenant de la production de métabolites par la cellule elle-même. Ces agressions induisent des dommages dans l'ADN. Ces dommages, s'ils ne sont pas réparés correctement, peuvent induire un dérèglement des fonctions de base de la cellule qui peut alors devenir cancéreuse. Pour réparer leur ADN, les cellules activent divers mécanismes de réparation et établissent une signalisation au niveau des sites endommagés. Dans le noyau, l'ADN est associé à des protéines appelées histones pour former la chromatine. La chromatine se caractérise par différents niveaux d'organisation, aboutissant à la formation d'une structure très compacte. Cette compaction élevée de la chromatine peut représenter une barrière pour la machinerie de réparation. En effet, pour être réparé, l'ADN endommagé doit être accessible à la machinerie de réparation. Pour cela, les cellules ont développé des mécanismes permettant d'accéder à l'ADN endommagé. Ces mécanismes de réponse aux dommages à l'ADN impliquent l'activation de voies de signalisation. L'un des signaux précurseurs activés après dommage à l'ADN est la Poly-ADP-Ribosylation (PARylation). La PARylation est une modification post-traductionnelle composée d'une répétition de petites molécules appelées Poly-ADP-Riboses, qui s'accrochent notamment sur les histones pour signaler la présence de cassures dans l'ADN et permettent ainsi de recruter les protéines impliquées dans la réparation des dommages. Lorsque l'ADN est endommagé, l'activation de processus de réparation induit de manière précoce le recrutement de facteurs de remodelage de la chromatine. Le rôle exact de la signalisation via la PARylation durant les étapes précoces de la réponse aux dommages à l'ADN et plus particulièrement lors du remodelage de la chromatine reste encore mal caractérisé. Durant ma thèse, j'ai utilisé des techniques avancées en microscopie pour étudier la dynamique de la chromatine après induction de dommages à l'ADN. J'ai ainsi tenté d'élucider le rôle de la PARylation dans le mécanisme de remodelage de la chromatine au niveau des dommages dans l'ADN, en recherchant des facteurs permettant d'altérer de manière spécifique la dynamique de la chromatine. Cette méthodologie nous a permis d'identifier différents facteurs impliqués dans le remodelage de la chromatine après dommage à l'ADNIn each human cell, many thousands of DNA lesions arise every day, challenging continuously the genome integrity. The majority of these lesions results from byproducts of normal cell metabolism or DNA replication, but they are also induced by exposure to radiations and genotoxic chemicals. The integrity of the genome is preserved by a plethora of different DNA damage signalling and repair machinery arranged by the cells. In the cell nucleus, DNA associates with scaffolding proteins to form the chromatin. The chromatin is tightly packed in the nucleus through several levels of organization. Such high-packing state poses a significant challenge for the repair machinery. Indeed, the damaged DNA needs to be accessible to repair proteins, and for that, cells have developed several mechanisms to allow the access to the damaged chromatin. The early steps of the DNA damage response involve the activation of proteins that are part of signalling pathways. One of the proteins activated upon DNA damage is PARP1, which synthetizes long and branched chains of ADP-ribose (poly-ADP-ribose or PAR) on itself and other chromatin factors, including histones. The activation of PARP1 leads to the recruitment of several effectors involved in DNA repair and chromatin remodeling. However the exact function of the PAR-signalling during early DNA damage response and in particular during chromatin remodeling at DNA breaks remains unclear. During my PhD, I used advanced fluorescent imaging tools to study in living cells the dynamics of chromatin in the nucleus at a local scale upon DNA damage. I used these tools to study PAR-dependent chromatin relaxation after DNA damage and to screen factors that selectively alter the dynamic behaviour of the damaged chromatin. This methodology allowed us to identify PAR-dependent factors involved in the local chromatin remodeling upon DNA damage
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Krietsch, Jana. "PARP-1 activation regulates the DNA damage response to DNA double-strand breaks." Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30722/30722.pdf.
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Les cassures double-brin de l'ADN, lorsque incorrectement réparées, peuvent avoir des conséquences fatales telles que des délétions et des réarrangements chromosomiques, favorisant la carcinogenèse. La poly(ADP-ribosyl)ation réalisée par la protéine poly(ADP-ribose) polymérase-1 (PARP-1) est l'une des premières modifications post-traductionnelles qui se produisent en réponse aux dommages à l'ADN. La PARP-1 utilise la nicotinamide pour générer un polymère chargé négativement, nommé poly(ADP-ribose) polymère (PAR), lequel est attaché en majorité à la PARP-1 elle-même ainsi qu'à d'autres protéines cibles. Le PAR a récemment été reconnu comme un signal de recrutement pour certaines protéines de réparation aux sites de dommages à l'ADN, mais un débat est en cours quant au rôle précis de la PARP-1 et du PAR dans la réponse aux dommages de l'ADN. Au cours de mon projet de doctorat, nous avons pu confirmer que les protéines qui se retrouvent en complexe avec le PAR immédiatement après les dommages à l'ADN sont principalement des facteurs de réparation. Étonnamment, les complexes protéiques associés au PAR pendant la période de récupération suite aux dommages sont enrichis en facteurs de liaison à l'ARN. Toutefois, la protéine liant l'ARN la plus abondante que nous avons détectée dans l'interactome du PAR, soit NONO, ne suit pas cette dernière cinétique puisqu'elle est fortement enrichie immédiatement après les dommages à l'ADN. Notre étude subséquente de NONO dans la réponse aux cassures double-brin de l'ADN a étonnamment révélé une implication directe de celle-ci par le mécanismede réparation de jonction des extrémités non-homologues. En plus, nous avons constaté que NONO se lie fortement et spécifiquement au PAR via son motif 1 de la reconnaissance de l'ARN, soulignant la compétition entre les PAR et l'ARN pour le même site de liaison. Fait intéressant, le recrutement in vivo de NONO aux sites de dommages de l'ADN dépend entièrement du PAR et nécessite le motif 1 de la reconnaissance de l'ARN. En conclusion, nos résultats établissent NONO comme une nouvelle protéine impliquée dans la réponse aux cassures double-brin de l'ADN et plus généralement démontrent un autre niveau de complexité supplémentaire dans l'interdépendance de la biologie de l'ARN et la réparation de l'ADN.DNA double-strand breaks are potentially lethal lesions, which if not repaired correctly, can have harmful consequences such as carcinogenesis promoted by chromosome deletions and rearrangements. Poly(ADP-ribosyl)ation carried out by poly(ADP-ribose) polymerase 1 (PARP-1) is one of the first posttranslational modifications occurring in response to DNA damage. In brief, PARP-1 uses nicotinamide to generate a negatively charged polymer called poly(ADP-ribose) polymer (PAR), that can be attached to acceptor proteins, which is to a large extent PARP-1 itself. PAR has recently been recognized as a recruitment signal for key DNA repair proteins to sites of DNA damage but the precise role of PARP-1 and its catalytic product PAR in the DNA damage response are still a matter of ongoing debate. Throughout my doctoral work, we confirmed that the proteins in complex with PAR promptly after DNA damage are mostly DNA repair proteins, whereas during the period of recovery from DNA damage, the PAR interactome is highly enriched with RNA processing factors. Interestingly, one of the most abundant RNA-binding proteins detected in the PAR interactome, namely NONO, did not follow these kinetics as it was highly enriched immediately after DNA damage in the DNA repair protein complexes centered on PAR. Our subsequent investigation of NONO in the DNA damage response to double-strand breaks strikingly revealed a direct implication for NONO in repair by nonhomologous end joining (NHEJ). Moreover, we found that NONO strongly and specifically binds to PAR through its RNA-recognition motif 1 (RRM1), highlighting competition between PAR and RNA for the same binding site. Remarkably, the in vivo recruitment of NONO to DNA damage sites completely depends on PAR and requires the RRM1 motif. In conclusion, our results establish NONO as a new protein implicated in the DNA damage response to double-strand break and in broader terms add another layer of complexity to the cross-talk between RNA-biology and DNA repair.
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Jowsey, Paul Andrew. "The role of poly(ADP-ribose) polymerase-1 in the MDM2-p53 DNA damage response pathway." Thesis, University of Newcastle Upon Tyne, 2003. http://hdl.handle.net/10443/1005.
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p53 is a tumour suppressor protein that is stabilised and activated by DNA damage. DNA damage-induced p53 is able to bring about either cell cycle arrest or apoptosis by the induction of p53-responsive genes such as mdm2 and p21 waf-I. Mdm2 regulates p53 function by blocking the transcriptional transactivation domain of p53 and also by targeting p53 for degradation via an ubiquitin-mediated pathway. Increases in the levels and activity of p53 are brought about by post-translational modifications. The most widely studied modification of p53 is phosphorylation, mediated by several DNA damageactivated kinases. Poly(ADP-Ribose) Polymerase-l (PARP-l) is also a DNA damageactivated enzyme which covalently modifies several target proteins by poly(ADPribosylation). It is well established that PARP-1 plays a key role in DNA base excision repair. More recently, several studies have implicated PARP-1 in the regulation of p53 function in response to DNA damage, although the nature of this relationship has been controversial. This study aimed to clarify and investigate further the role of PARP-1 in p53 regulation using PARP-1 proficient and PARP-1 deficient mouse embryonic fibroblasts (MEFs) as well as a novel potent PARP-1 inhibitor (AGI4361; Ki < 6nM). In this study, both primary and immortalised PARP-l MEFs were used. Initial experiments revealed a tendency for PARP-l +/+ MEFs to develop p53 mutations during immortalisation. Interestingly. PARP-1 -/- MEFs retained wild-type p53, suggesting that the absence of PARP-l bypasses the requirement for p53 to be mutated during the immortalisation of MEFs. As these cells could not be used to analyse p53 responses, experiments were perfonned on primary PARP-l MEFs. However. the primary PARP-l- - MEFs were found to grow very slowly compared to their PARP-1 proficient counterparts. Interestingly. treatment of primary PARP-1+1+ MEFs with AG14361 had a similar effect on cellular growth. This growth inhibition in the absence of PARP-1 was only evident in primary and not immortalised cells. It was therefore decided to stably transfect immortalised PARP-l-- MEFs, expressing wild-type p53, with a plasmid construct containing PARP-l to produce an isogenic cell line pair. These cells have been used, together with a human colorectal carcinoma cell line (HCT-116) and the potent PARP-1 inhibitor AG14361 to analyse the p53 response to different DNA damaging agents. In response to ionising radiation and ultra violet radiation, the absence of PARP-1 did not alter the induction or activity of p53. In response to the alkylating agent temozolomide, treatment of PARP-l proficient MEFs with AG14361 potentiated the increase in p53 protein levels without affecting the transcriptional transactivation activity of p53, possibly due to an impaired repair of the DNA damage and hence increased signalling to p53 due to the persistence of DNA strand breaks. However, similar results were not obtained in the absence of PARP-1 protein (P ARP-1-/- MEFs) or in HCT -116 cells treated with AG 14361 The data presented do not support the hypothesis that PARP-1 is directly involved in the DNA damage induced regulation of p53. There may, however, be an altered p53 response in the absence of PARP-l when cells are treated with particular DNA damaging agents, due to an impaired DNA repair pathway.
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Grauer, Christine M. "The effects of zinc status on hepatic poly(ADP-ribose) polymerase function in response to DNA damage." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq24472.pdf.
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Wu, Wing-Fung. "Structural studies of the molecular mechanism of DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648786.
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Pacella, Manuela. "Pulsed laser ablation (PLA) of ultra-hard structures : generation of damage-tolerant freeform surfaces for advanced machining applications." Thesis, University of Nottingham, 2014. http://eprints.nottingham.ac.uk/27730/.
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The current methods for manufacturing super-abrasive elements result in a stochastic geometry of abrasives with random three-dimensional abrasive spatial locations. This thesis covers the laser generation of novel micro-cutting arrays in ultra-hard super-abrasive composites (e.g. polycrystalline diamond, PCD and polycrystalline cubic boron nitride, PCBN). Pulsed laser ablation (PLA) has been used to manufacture repeatable patterns of micro cutting/abrasive edges onto micro structurally different PCD/PCBN composites. The analysis on the influence of microstructural factors of the composite materials in the use of laser ablation technology has been carried out via a novel technique (Focused Ion Beam/High Resolution Transmission Electron Microscopy/Electron Energy Loss Spectroscopy) to identify the allotropic changes occurring in the composite as a consequence of PLA allowing the laser ablated PCD/PCBN surfaces to be characterized and the nanometric changes evaluated. The wear/failure characteristics/progression of the ultra-hard laser generated micro cutting/abrasive arrays has been studied in wear tests of Silicon Dioxide workpiece shafts and the influence of the microstructural factors in the wear properties of the super-abrasive micro cutting edges has been found. Opposing to these highly-engineered microcutting/abrasive arrays, conventional electroplated abrasive pads containing diamond and CBN abrasives respectively have been chosen as benchmarks and tested under the same conditions. Contact profiling, Optical Microscopy and Environmental Scanning Electron Microscopy have been employed for the characterization of the abrasive arrays/electroplated tools before/during/after the wear/cutting tests. In the PCD abrasive micro-arrays, the type of grain and binder percentage proved to affect the wear performances due to the different extents of compressive stresses occurring at the grain boundaries. In this respect, the micro-arrays made of PCD with mixed diamond grains have shown slower wear progression when compared to the electroplated diamond pads confirming the combination of the high wear resistance typical of the fine grain and the good shock resistance typical of the coarse grain structures. While PCD laser manufactured arrays indicated edge break as typical wear mechanism, the abrasive pad confirmed flattening of grits as main wear mechanism. Mixed grained PCD arrays performed 25% better than fine grained arrays. The improved wear performances of laser manufactured arrays when compared to industrial benchmark is proved by the different wear failure mechanism in the array and in the electroplated pad: in the first one the edges break creating new sharp edges during testing, while in the latter grit flattening is the main wear mechanism. This increases up to 60% the life of the laser manufactured array when compared to the benchmarked pads. As for the PCBN abrasive micro-arrays, two are the main wear mechanisms experienced by the arrays: edge flattening for the high CBN content array and edge breaking for the medium CBN content array. The wear performance of the high content PCBN array is directly comparable to the electroplated boron nitride pad, because they both worn out with edge/grit flattening. The increase of metallic binder and the presence of metalloids in the medium content-CBN specimens have shown to produce higher contact pressure with the workpiece when compared to the electroplated specimen, causing fracturing as the main wear mechanism; while the PCBN micro-array with purely a metallic binder phase has shown better wear performances and lower contact pressure in comparison to the electroplated CBN specimen. In particular, the laser manufactured array proved to perform 50% better than the electroplated ones in terms of wear resistance. Among all of the tested arrays, the mixed grained PCD and the purely metallic binder phase PCBN micro-arrays have shown slower wear when benchmarked to the electroplated pads, giving a possible application of their use in the cutting tool industry.
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Albalawi, Mohammed Hamdan. "READ TO CHANGE: THE ROLE ARABIC LITERATURE CAN PLAY TO REDRESS THE DAMAGE OF STEREOTYPING ARABS IN AMERICAN MEDIA." Kent State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=kent1460221387.
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Veuger, Stephany Jane. "Interactive effects of poly(ADP-ribose) polymerase -1 and DNA dependent protein kinase in the cellular responses to DNA damage." Thesis, University of Newcastle Upon Tyne, 2003. http://hdl.handle.net/10443/1023.
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DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase-1 (PARP-1) participate in non-homologous end joining and base excision repair respectively, and are key determinants of radio-resistance. The interactive effects of PARP-1 and DNA-PK in the cellular responses to DNA damage were investigated using novel specific inhibitors of DNA-PK (NU7026) and PARP-1 (AG14361) and cell lines proficient or deficient for DNA-PK or PARP-1. Enzyme deficient cell lines were 4-fold more sensitive to ionizing radiation (IR) alone, and showed reduced potentially lethal damage recovery (PLDR), compared to their proficient counterparts. NU7026 potentiated IR cytotoxicity in exponentially growing DNA-PK proficient, but not deficient cells. Similarly AG14361 potentiated IR in PARP-1 +/+ but not PARP-1-/- cells. When NU7026 and AG14361 were used in combination, their potentiating effects were additive. Both inhibitors reduced PLDR in the proficient cell lines. Furthermore, inhibitor combination completely abolished PLDR. Both inhibitors prevented IR-induced DNA double strand break repair, but only AG14361 prevented DNA single strand break repair The enzyme activities were investigated using purified enzymes and permeabilised cells. In cell-free assays, PARP- 1 activity was unaffected by the presence of DNA-PK, and vice versa, provided the enzyme substrates were present. DNA-PK inhibited PARP-1 when ATP was absent or NU7026 present. PARP-1 inhibited DNA-PK when NAD+ was absent or AG14361 present. Furthermore, PARP-1 inhibition increased with increasing ratio of DNA-PK to PARP-1, and vice versa. Similar results were obtained using the inhibitors in permeabilised cells. PARP-1 was inactive in the absence of histones, but activity was restored by the addition of DNA-PK. DNA-PK was inactive in the absence of its p53 peptide substrate unless PARP-1 was included. These data suggest reciprocal regulation of PARP-1 and DNA-PK, and co-operation in DSB repair and survival. Thus, individually, or in combination, the DNA-PK and PARP-1 inhibitors act as potent radio-sensitisers.
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Verma, Ravi Kant. "A study of the damage accumulation process in poly(aryl ether ketone ketone) and its AS4 carbon fiber reinforced composites." Thesis, Virginia Tech, 1992. http://hdl.handle.net/10919/43146.
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This thesis presents the results of a study done on the damage accumulation process in poly(ether ketone ketone) and its AS4 carbon fiber reinforced composites. The damage accumulation process was studied as a function of applied heat treatment. This study is the result of a project funded by duPont and was done in part to explain the dramatic change in fatigue properties observed at duPont as the applied heat treatment is changed.
The mechanical properties were characterized using a battery of tests. The quenched composite systems have lower moduli, but higher toughness and elongations. The quenched systems also have the best fatigue performance and therefore, it can be concluded that the quenched composite systems have the best potential as far as industrial applications are concerned. Quenching has other advantages in industrial applications. These include decreased chances of operator error, and decreased processing times.
The damage accumulation process was characterized using the acoustic emission method and also the drop in stiffness during flexure testing. It has been observed that the ultimate mechanical properties show a weak dependence on the applied heat treatment, whereas the damage accumulation process changes dramatically. A model has been developed to simulate the damage accumulation process. This model has then been used to predict the fatigue S-N curve in stroke control and to qualitatively relate it to the available fatigue data in stress control.Master of Science
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Harris, Edward T. "The effect of solvent damage and fibre waviness on the strength of cross-plied carbon fibre reinforced poly(aryl sulphone)." Thesis, University of Central Lancashire, 1996. http://clok.uclan.ac.uk/20020/.
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The effect of damage on carbon-fibre reinforced poly(aryl suiphone) by a solvent of the type used by BAe Military Aircraft Division as a paint stripper has been investigated together with the effect of fibre waviness upon the mechanical strength of carbon-fibre reinforced poly(aryl suiphone). Mathematical models for solvent effects were derived and comparison was made with the practical results obtained both from tension loading and three-point loading in bending. Good agreement between the theoretical and test results has been observed. It was found that solvent damage is minimal on the tensile behaviour of (90,0)s laminates but caused a reduction in the strain at failure in (0,90)s laminates. Theoretical models were developed for fibre waviness, where the waviness is in the plane of the ply. The theoretical results are compared to the results of tensile testing. It is reported that, contrary to the work of others, fibre waviness can have a marked affect on laminate behaviour in tension and, for a wave ratio of 0.1, can cause the load at failure in cross-plied laminates to be reduced to only 24% of the the load at failure in an equivalent laminate free of fibre waviness. Specimens were put through heating and cooling cycles in order to reduce residual stresses. Estimates of the value of these stresses were based upon the curvature of asymmetric laminates. The results compared favourably with published values for similar materials. Various 'protective' coats were investigated to reduce the amount of solvent damage. One protective coat was found to give reduced damage with increasing coats. Test results were compared to those obtained from (i) The Tsai-Hill failure criterion, (ii) The Han-Smith maximum shear stress criterion. The test results were found to be in good agreement with both criteria when failure did not occur at positions containing fibre waviness. When failure occurs at fibre waviness it is demonstrated that if the exact point of failure within fibre waviness is known then corrections can be made to the test results. When the corrections were made there was good agreement between test results and both criteria.
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Verma, Ravi Kant. "A study of the damage accumulation process in poly(aryl ether ketone ketone) and it's [sic] AS4 carbon fiber reinforced composites /." This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-06112009-063316/.
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Hetti, Mimi. "Synthesis and Characterization of Polymeric Magnetic Nanocomposites for Damage-Free Structural Health Monitoring of High Performance Composites." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2016. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-211082.
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The poly(glycidyl methacrylate)-modified magnetite nanoparticles, Fe3O4-PGMA NPs, were investigated and applied in nondestructive flaw detection of polymeric materials in this research. The Fe3O4 endowed magnetic property to the materials for flaw detection while the PGMA promoted colloidal stability and prevented particle aggregation. The magnetite nanoparticles (Fe3O4 NPs) were successfully synthesized by coprecipitation and then surface-modified with PGMA to form PGMA-modified Fe3O4 NPs by both grafting-from and grafting-to approaches. For the grafting-from approach, the Fe3O4 NPs were surface-functionalized with α-bromo isobutyryl bromide (BIBB) to form BIB-modified Fe3O4 NPs (Fe3O4-BIB NPs) with covalent linkage. The resultant Fe3O4-BIB NPs were used as surface-initiators to grow PGMA by surface-initiated atom transfer radical polymerization (SI-ATRP). For the grafting-to approach, the Fe3O4 NP were surface-functionalized with (3-mercaptopropyl)triethoxysilane (MCTES) to form MCTES-modified Fe3O4 NPs (Fe3O4-MCTES NPs). The PGMA with Br-end group was pre-synthesized by ATRP and then was grafted to the surface of the Fe3O4-MCTES NPs by coupling reaction.
Both bare and modified Fe3O4 NPs exhibited superparamagnetism and the existence of iron oxide in the form of Fe3O4 was confirmed. The particle size of individual Fe3O4 NPs was about 8 – 24 nm but they aggregated to form clusters. The PGMA-modified NPs formed stable dispersion in chloroform and had larger cluster sizes than the unmodified ones because of the PGMA polymer layer. However, the uniformity of the NP clusters could be improved with PGMA surface grafting. The PGMA surface layer of the grafting-from (Fe3O4-gf-PGMA) NPs was thin and dense while that of the grafting-to (Fe3O4-gt-PGMA) NPs was thick and loose. The hydrodynamic diameters (Zave) of Fe3O4-gf-PGMA NP clusters could be controlled between 176 to 643 nm, dependent on the PGMA contents and reaction conditions. During SI-ATRP, side reactions happened and caused NP aggregation as well as increase of size of NP clusters. However, the aggregation has been minimized through optimization of reaction conditions. Oppositely, Zave values of Fe3O4-gt-PGMA NPs had little variation of about 120 – 190 nm. And the PGMA content of the Fe3O4-gt-PGMA NPs was limited to 12.5% because of the spatial hindrance during grafting process.
The saturation magnetization (Ms) of the unmodified Fe3O4 NPs was about 77 emu/g, while those of the grafting-from and grafting-to Fe3O4-PGMA NPs were 50 – 66 emu/g and 63 – 70 emu/g, respectively. For Fe3O4-PGMA NPs with similar Fe3O4 contents, the grafting-to NPs had slightly higher Ms than the grafting-from counterparts. In addition, the Ms of both kinds of the Fe3O4-PGMA NPs with higher Fe3O4 content (> 87%) were also higher than that of the fluidMAG-Amine, the commercially available amine-modified MNPs. Besides, both kinds of Fe3O4-PGMA NPs also had much higher Fe3O4 contents and Ms values than most of the reported PGMA-modified MNPs.
The magnetic epoxy nanocomposites (MENCs) were prepared by blending the modified Fe3O4 NPs into bisphenol A diglycidyl ether (BADGE)-based epoxy system and the distributions of both kinds of the PGMA-modified NPs were much better than that of the oleic acid-modified Fe3O4 NPs. Similar to the NPs, the MENCs also exhibited superparamagnetism. By cross-section TEM observation, the grafting-to Fe3O4-PGMA NPs formed more homogeneous distributions with smaller cluster size than the grafting-from counterparts and gave higher Ms of the MENCs. Nondestructive flaw detection of surface and sub-surface defects could be successfully achieved by brightness contrast of images given through eddy current testing (ET) method, which is firstly reported. The mechanical properties of the materials were influenced very slightly when 2.5% or lower Fe3O4-gt-PGMA NPs were present while the presence of the Fe3O4-gf-PGMA NPs (1 – 2.5 %) gave mild improvement of the storage modulus and increase of the glass-rubber transition temperature(Tg) of the MENCs. Furthermore, the Fe3O4-PGMA NPs could be evenly coated onto the functionalized ultra-high molecular weight poly(ethylene) (UHMWPE) textiles. The Fe3O4-gt-PGMA NPs were coated on the textile in order to prepare NP-coated textile-reinforced composite. Preliminary result of ET measurement showed that the Fe3O4-gt-PGMA NPs coated on the textiles could visualize the structure of the textile hidden inside and their relative depth. Accordingly, the incorporation of MNPs to polymers opens a new pathway of damage-free structural health monitoring of polymeric materials.
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Lebeaupin, Théo. "Multiscale analysis of poly-ADP-ribosylation dependent chromatin remodeling mechanisms at DNA breaks." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1B024/document.
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Pendant longtemps, la chromatine a été uniquement décrite comme un moyen de compacter près de deux mètres d’ADN dans un noyau de quelques micromètres de diamètre. On sait aujourd’hui que la chromatine représente en fait un élément majeur de régulation de toutes les fonctions nucléaires impliquant l’ADN. Dans le contexte de dommages de l’ADN induits par irradiations UV, la chromatine endommagée subit une décondensation rapide et transitoire qui l’amène à occuper un volume 1,5 fois plus grand que son volume initial. Cette relaxation chromatinienne est associée à une plus grande accessibilité de l’ADN. Néanmoins, le lien entre ces deux effets découlant de la présence de dommages, n’a pas été établi, ni caractérisé. En couplant l’imagerie de cellules vivantes à l’induction de dommages ciblés au sein de noyaux cellulaires par micro-irradiation laser, ces travaux ont permis de mettre en évidence le rôle majeur de PARP1 dans la réponse chromatinienne aux dommages de l’ADN. En effet, certaines conclusions contradictoires présentes dans la littérature scientifique concernant l’action de PARP1 sur la chromatine ont été réconciliées en démontrant que PARP1 seul peut se lier à la chromatine et entraîner une plus forte compaction de celle-ci, tandis que son activité catalytique de PARylation va, quant à elle, conduire à une décompaction de la structure chromatinienne. Cette étude s’est aussi intéressée à la dynamique particulière de l’histone H1 suite aux dommages de l’ADN. En effet, celui-ci est rapidement exclu des zones de dommages par un mécanisme encore inconnu, et les éléments apportés ici suggèrent que H1 pourrait jouer un rôle dans la décondensation de la chromatine suite aux dommages de l’ADN. Pour finir, des techniques de photo-perturbation et de spectroscopie de corrélation de fluorescence ont été employées pour comprendre et caractériser l’environnement moléculaire que constitue la chromatine endommagée et décondensée. Bien qu’une augmentation significative des interactions entre la chromatine et certains de ses partenaires d’interactions soit observée au sein des zones endommagées, aucun changement en termes d’encombrement moléculaire n’a pu être mis en évidence à ce niveau qui pourrait expliquer une plus grande accessibilité de l’ADNFor a long time, chromatin was only described as a mean to fit the two-meters long DNA molecule into a nucleus of only a few microns. It is admitted today that chromatin actually represents a key element in the regulation of all nuclear functions dependent on DNA. In the context of UV-induced DNA damage, chromatin undergoes a rapid and transient relaxation which leads to an expansion of the damaged area to 1.5 times its original size. While this chromatin response to damage is associated with a higher DNA accessibility, the link between those two phenomena, as well as the mechanisms driving them, are still poorly understood. Using live-cell imaging and laser micro-irradiation to induce DNA damage on specific nuclear areas, this work allowed to gain hindsight on the predominant role played by PARP1 in the DNA damage-induced chromatin relaxation. Indeed, showing that PARP1 at DNA damage sites can both induce chromatin compaction through its recruitment at DNA breaks or chromatin decondensation through its PARylation activity helped reconcile its apparent opposite effects described in the literature. A focus was also made on the linker histone H1, as it displays a peculiar behavior upon DNA damage, being rapidly released from the site of DNA lesions. Even if the driving force behind H1 release from damaged chromatin areas has not been identified yet, its behavior suggests that H1 might play a part in chromatin relaxation or in increasing DNA accessibility upon DNA damage. Lastly, combining photo-activation techniques and fluorescence correlation spectroscopy, experiments were performed in order to understand the physical environment that damaged, relaxed chromatin constitutes. We report here that, while enhanced binding of random DNA binding factors is observed in the damaged chromatin area, no significant change is observed in the macromolecular crowding levels that could potentially explain this enhanced binding, as well as a higher DNA accessibility
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Colona, Ortega José Carlos. "Is the Accreditation of an Arbitrary Dismissal Sufficient to result in the Payment of Compensation for Moral Damages?" Derecho & Sociedad, 2017. http://repositorio.pucp.edu.pe/index/handle/123456789/117688.
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The author analyzes the rules of civil liability and its application in the workplace to establish the right to compensation as a result of irregular dismissal. In particular, it seeks to determine if a judicial declaration of unfair dismissal is sufficient to justify the payment of compensation for moral damages for the worker element.El autor realiza un análisis de las reglas de la responsabilidad civil y su aplicación en el ámbito laboral para establecer el derecho a ser indemnizado como consecuencia de un cese irregular. En particular, busca determinar si es que una declaración judicial de despido arbitrario es un elemento suficiente para justificar el pago de una indemnización por daño moral a favor del trabajador.
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Marquez, Rafael Batista. "Cláusula take or pay em contratos de longo prazo." reponame:Repositório Institucional do FGV, 2018. http://hdl.handle.net/10438/22992.
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O escopo deste trabalho consiste na análise do racional e do funcionamento da cláusula take or pay, largamente utilizada em contratos de longo prazo, usualmente em contratos de fornecimento. Para tanto, tratar da tipicidade (social) da cláusula take or pay mostrou-se necessário. Isso porque, abordou-se a qualificação e interpretação da obrigação decorrente da cláusula e a sua finalidade, tendo em vista a boa-fé objetiva e o dever de cooperação entre as partes. Indo além, abordou-se a natureza jurídica da cláusula take or pay, considerando a inafastável e necessária prefixação dos valores a serem pagos em caso de descumprimento da obrigação. Na sequência, analisou-se a aplicabilidade do artigo 413 do Código Civil. Por derradeiro e a fim de apresentar aspectos propositivos, abordou-se a importância do cuidado com a redação contratual, bem como algumas recomendações práticas sobre a cláusula take or pay, endereçando algumas preocupações quando do seu uso, ainda pouco amadurecido no Brasil. Assim, acredita-se que o presente estudo contribuirá para o desenvolvimento do uso da cláusula de forma previsível e respeitando a segurança jurídica almejada nas relações contratuais.
This work consists on the analysis of the rationale and practice of take or pay clause, widely applied in long-term contracts, usually in supply agreements. To do so, dealing with the typicity (social) of the take or pay clause was necessary. It was taken into account the qualification and interpretation of the obligation provided in the clause and its purpose, vis-à-vis the good faith principle and the cooperation duty between the parties. Beyond that, this study aimed to address the legal nature of take or pay clause, as the due values are pre-determined (liquidated damages) in case of default. In addition to that, for a comprehensive understanding, the study also evaluated the applicability of article 413 of the Brazilian Civil Code The study propositional approach focused on the importance of the contract wording and recommends some practical measures for the clause legal writing, which is still incipient in Brazil. Based on that, the author believes that this study may contribute to enable the development of the take or pay clause in a predictable manner respecting the legal safety in the contractual relations.
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Bentle, Melissa Srougi. "INVOLVEMENT OF SINGLE- AND DOUBLE-STRAND BREAK REPAIR PROCESSES IN BETA-LAPACHONE-INDUCED CELL DEATH." Connect to text online, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1179427756.
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da, Silva Soares Joao Filipe. "Constitutive modeling for biodegradable polymers for application in endovascular stents." Texas A&M University, 2008. http://hdl.handle.net/1969.1/85939.
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Percutaneous transluminal balloon angioplasty followed by drug-eluting stent
implantation has been of great benefit in coronary applications, whereas in peripheral
applications, success rates remain low. Analysis of healing patterns in successful
deployments shows that six months after implantation the artery has reorganized itself to
accommodate the increase in caliber and there is no purpose for the stent to remain,
potentially provoking inflammation and foreign body reaction. Thus, a fully
biodegradable polymeric stent that fulfills the mission and steps away is of great benefit.
Biodegradable polymers have a widespread usage in the biomedical field, such as
sutures, scaffolds and implants. Degradation refers to bond scission process that breaks
polymeric chains down to oligomers and monomers. Extensive degradation leads to
erosion, which is the process of mass loss from the polymer bulk. The prevailing
mechanism of biodegradation of aliphatic polyesters (the main class of biodegradable
polymers used in biomedical applications) is random scission by passive hydrolysis and
results in molecular weight reduction and softening.
In order to understand the applicability and efficacy of biodegradable polymers, a
two pronged approach involving experiments and theory is necessary. A constitutive
model involving degradation and its impact on mechanical properties was developed
through an extension of a material which response depends on the history of the motion
and on a scalar parameter reflecting the local extent of degradation and depreciates the
mechanical properties. A rate equation describing the chain scission process confers
characteristics of stress relaxation, creep and hysteresis to the material, arising due to the entropy-producing nature of degradation and markedly different from their viscoelastic
counterparts.
Several initial and boundary value problems such as inflation and extension of
cylinders were solved and the impacts of the constitutive model analyzed. In vitro
degradation of poly(L-lactic acid) fibers under tensile load was performed and
degradation and reduction in mechanical properties was dependent on the mechanical
environment. Mechanical testing of degraded fibers allowed the proper choice of
constitutive model and its evolution. Analysis of real stent geometries was made possible
with the constitutive model integration into finite element setting and stent deformation
patterns in response to pressurization changed dramatically as degradation proceeded.
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Heberle, Eléa. "Etude du rôle et de la régulation de la Poly(ADP-ribose) Glycohydrolase(PARG) dans la réponse cellulaire aux dommages à l'ADN." Thesis, Strasbourg, 2017. http://www.theses.fr/2017STRAJ106.
Full textAbstract:
La Poly(ADP-ribosyl)ation est une modification post-traductionnelle de protéines, impliquée dans un grand nombre de processus biologiques, dont la réparation de l’ADN. Alors que la fonction et le mode d’action de la Poly(ADP-ribose) (PAR) Polymérase 1 (PARP1), activée en réponse aux dommages de l’ADN sont bien compris, on en sait beaucoup moins sur la fonction et la régulation de l’enzyme de dégradation du PAR, la Poly(ADP-ribose) glycohydrolase (PARG). Dans le contexte de ce projet de thèse, nous décrivons de nouvelles lignées U2OS stables, déficientes pour toutes les isoformes de PARG, permettant la complémentation inductible avec chacun des isoformes de PARG. Ces modèles nous ont permis d’évaluer les contributions relatives des isoformes à la réparation de dommages à l’ADN. Nous avons identifié un nouveau partenaire cellulaire de PARG : la protéine-kinase dépendante des dommages à l’ADN (DNA-PK). Nous explorons l’interaction fonctionnelle de ces deux protéines dans le contexte de la réponse cellulaire à la camptothécine (CPT), un agent anticancéreux inhibant la topoisomérase I et provoquant l’activation simultanée de PARP1 et DNA-PKPoly (ADP-ribosyl) ation is a post-translational modification of proteins involved in a large number of biological processes, including DNA repair. While the function and mode of action of Poly (ADP-ribose) (PAR) Polymerase 1 (PARP1), activated in response to DNA damage, is well understood, much less is known about the function and regulation the PAR degrading enzyme, Poly (ADP-ribose) glycohydrolase (PARG). In the context of this thesis project, we describe new stable U2OS lines, deficient for all PARG isoforms, allowing the inducible complementation with each of the PARG isoforms. These models allowed us to evaluate the relative contributions of the isoforms to DNA damage repair. We have identified a new cellular partner of PARG: the DNA-dependent protein kinase-dependent kinase (DNA-PK). We explore the functional interaction between these two proteins in the context of the cellular response to camptothecin (CPT), an anticancer drug that inhibits topoisomerase I and induces the simultaneous activation of PARP1 and DNA-PK
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Vernin, Emmanuelle Reynaud Jean-François. "Les bâtiments canoniaux du chapitre cathédral Notre-Dame du Puy-en-Velay un centre "fortifié" de vie communautaire, intellectuelle et de spiritualité (Xe-début XVI siècles) /." Lyon : Université Lumière Lyon 2, 2003. http://demeter.univ-lyon2.fr:8080/sdx/theses/lyon2/2003/vernin_e.
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Caous, Damien. "Rôle de l'endommagement sur la durée de vie en fatigue des matériaux composites stratifiés : application au domaine éolien." Thesis, Paris, ENSAM, 2017. http://www.theses.fr/2017ENAM0022/document.
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L’objet de cette thèse est de proposer et d’identifier un modèle de comportement mécanique en fatigue écrit à l’échelle du pli ou de la couche composite élémentaire. Le modèle doit permettre de prédire l’évolution des dégradations mais également la résistance résiduelle. Les matériaux concernés par cette étude sont des composites renforcés par des tissus de fibres de verre bi ou tri axiaux. Ce travail exclue les zones de liaisons ou de reprise de pli où des contraintes hors plan engendrent des couplages forts entre endommagement intra et inter laminaires. Les principaux objectifs de la thèse sont de : - Identifier sur le matériau de l’étude les mécanismes d’endommagement et leur couplage en quasi-statique et en fatigue - Caractériser et modéliser la perte de rigidité engendrée par les mécanismes d’endommagement - Caractériser et modéliser les cinétiques d’endommagement en fatigue - Caractériser et modéliser les pertes de résistance engendrées par les mécanismes d’endommagement - Implémenter et tester le modèle proposé (ou celui retenu de la littérature et qui sera modifié si besoin) dans un code de calcul EFThe purpose of this thesis is to propose and identify a model of mechanical fatigue behavior written for the lamina level. The model would be able to predict damage evolution but also residual strength. Studied materials are bi or tri axial glass fibre reinforced plastics fabrics. This work excluded joints areas where out of plane stresses generate strong coupling between intra and inter laminar damage. The main goals of the thesis are: - Identify on the material of the study damage mechanisms and their coupling in quasi-static and fatigue - Characterize and model residual stiffness caused by damage mechanisms - Characterize and model fatigue damage - Characterize and model residual strength caused by damage mechanisms - Implement and test the proposed model (or the one chosen in the literature and changed if necessary) in a computer FE code
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Samuelsson, Oscar, and Pontus Svensson. "Kan aktieägaravtal som saknar aktiebolagsrättslig relevans leda till obligationsrättslig bundenhet och skadeståndsskyldighet? : De lege lata och de lege ferenda." Thesis, Internationella Handelshögskolan, Högskolan i Jönköping, IHH, Redovisning och Rättsvetenskap, 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-26623.
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Bestämmelsen om tvångsinlösen i 22 kap. 1 § ABL är tvingande, vilket innebär att avsteg från vad som föreskrivs inte får göras genom bolagsordningen. Mot bakgrund av Högsta domstolens avgörande i NJA 2011 s. 429, synes bestämmelsens tvingande natur vara än mer vidsträckt. I förevarande fall ansågs nämligen ett aktieägaravtal, varigenom en majoritetsägare avstått från sin rätt att påkalla tvångsinlösen, sakna aktiebolagsrättslig relevans. Domstolen framhöll emellertid att sådana aktieägaravtal som huvudregel binder parterna. Författarna är av uppfattningen att blotta förekomsten av tvångsinlöseninstitutet utgör en inskränkning av principen om avtalsfrihet. Därutöver innebär Högsta domstolens avgörande att den välgrundade principen inskränks ytterligare. I förevarande uppsats utreds huruvida den sistnämnda inskränkningen är motiverad. Därutöver utreds även hur ett eventuellt avtalsbrott och en därtill inträdande skadeståndsskyldighet förhåller sig till det faktum att avtalsvillkoret saknar aktiebolagsrättslig relevans. Inledningsvis anser författarna att inskränkningen av avtalsfriheten som följer av NJA 2011 s. 429 är motiverad. Vidare har författarna konstaterat att skadeståndsskyldighet kan aktualiseras de lege lata eftersom parterna torde vara obligationsrättsligt bundna mot bakgrund av Högsta domstolens uttalande i NJA 2011 s. 429. Yttermera är författarna av uppfattningen att ett föreliggande skadeståndsansvar inte kan begränsas genom tillämpning av adekvansläran eller normskyddsläran. De lege ferenda anser författarna att ett aktieägaravtal som inskränker tvångsinlösenrätten inte bör tillerkännas obligationsrättslig verkan. Detta främst mot bakgrund av att det är en orimlig följd att ett avtal som inte kan göras gällande gentemot bolaget trots allt kan föranleda obligationsrättslig bundenhet och skadeståndsansvar.The provision in chapter 22. 1 § of the Swedish companies act regarding compulsory purchases and sales of shares is imperative, meaning that derogations from the provision not is allowed through a company’s articles of association. The imperative nature of the provision has been further strengthened through the Swedish Supreme Court ruling NJA 2011 s. 429. In the mentioned case, a shareholders’ agreement in which a party has waived its right to claim a compulsory purchase, was found to lack affect in relation to the company. However, the court stressed that shareholders’ agreements, in principle, are valid and enforceable between the contractual parties, i.e. the shareholders. The authors’ opinion is that the mere existence of compulsory purchases and sales of shares constitute an infringement of the freedom of contract. Moreover, the mentioned court ruling entails an extension of the already existing infringement of this freedom. This thesis examines whether this, later infringement, is motivated. Furthermore, this thesis examines how a breach of a shareholders’ agreement – and liability to pay damages – relates to the fact that the contractual term that has been breached lacks affect toward the company. According to the authors, the infringement of the freedom of contract derived from the mentioned court ruling is motivated. Furthermore, the authors have concluded that liability to pay damages may arise de lege lata, due to the fact that the contractual parties ought to be bound by the shareholders’ agreement according to the mentioned court ruling. In the authors’ opinion, the methods used to limit liability are not capable of doing so in this case. The authors suggest, de lege ferenda, that a term of a shareholder’s agreement where a party refrains from his right to claim a compulsory purchase or sales of shares not shall be binding between the parties.
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Matta, Elie. "Characterization of DNA ADP-Ribosylation Mechanism and its Role in DNA Damage Signaling Insight into DNA Substrate Specificity of PARP1-Catalysed DNA Poly(ADP-Ribosyl)ation Role of PARP-catalyzed ADP-ribosylation in the Crosstalk Between DNA Strand Breaks and Epigenetic Regulation." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASS058.
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Les poly (ADP-ribose) polymérases dépendantes de l’ADN (PARPs) PARP1, PARP2 et PARP3 agissent comme des détecteurs de cassures d'ADN signalant des dommages à l'ADN. Lors de la détection des dommages à l'ADN, ces PARPs utilisent le nicotinamide adénine dinucléotide comme substrat pour synthétiser un monomère ou un polymère d'ADP-ribose (MAR ou PAR, respectivement) attaché de manière covalente au résidu accepteur des protéines cibles. Récemment, il a été démontré que les protéines PARP1–3 peuvent directement ADP-ribosyler les cassures d'ADN en attachant les oligomères MAR et PAR aux phosphates terminaux.Néanmoins, peu de choses sont connues sur les mécanismes régissant la reconnaissance et la spécificité du substrat de PARP1, qui représente la majeure partie de l'activité de PARylation cellulaire, ainsi que sur les protéines responsables de la détection et de l'élimination des adduits d'ADN ADP-ribosylés et son rôle dans une multitude de processus cellulaires. Dans cette étude, nous avons caractérisé de manière détaillée la spécificité du substrat (ADN) de PARP1 et des mécanismes de la PARylation de l'ADN. Nous avons montré que le résidu phosphate 3'-terminal aux extrémités des cassures de l'ADN double brin servait de site accepteur majeur pour la PARylation catalysée par PARP1 en fonction de l'orientation et de la distance entre les cassures du brin d'ADN dans une seule molécule d'ADN. De plus, une préférence pour l’ADP-ribosylation des molécules d'ADN contenant du phosphate 3'-terminal a été observée par rapport à l'auto-ADP-ribosylation de PARP1, et un modèle de modification de l'ADN par PARP1 a été proposé. Des résultats similaires ont été observés avec l’enzyme PARP1 recombinante purifiée et des extraits provenant des cellules HeLa. Ainsi, les effets biologiques de l’ADP-ribosylation médiée par PARP peuvent dépendre fortement de la configuration des cassures complexes des brins d'ADN. De plus, nous avons élaboré une nouvelle approche permettant d’identifier et valider les protéines responsables de la détection («readers») ou de l'élimination («erasers») des adduits ADN- ADP-ribose. Nos données protéomiques ont révélé que les adduits de l'ADN MARylé modulaient sélectivement la reconnaissance de l'ADN par un grand nombre de protéines impliquées dans différentes voies de signalisation cellulaire. Environ 90 protéines, y compris des complexes protéiques, ont été sélectionnées comme lecteurs («readers») potentiels d'adduits ADN-MARylé. Le rôle de l'ADP-ribosylation de l’ADN dans la jonction d'extrémités non homologues (NHEJ) a été partiellement caractérisé dans une étude in vitro. Nous avons démontré que l'ADP-ribosylation de l’extrémité de la cassure double brin («DSB») peut conduire à l'inhibition de la réparation de la DSB bout franc par la voie NHEJ canonique si elle n'est pas éliminée par la glycohydrolase PARG. Au contraire, la présence d'une coupure («nick») proximale avec un site apurinique / apyrimidinique stabilisé conduit à une efficacité NHEJ accrue, apparemment de manière indépendante de l'ADP-ribosylation. Enfin, nous avons recherché de nouveaux inhibiteurs de PARP1, PARP2 et PARP3 parmi les dérivés de 1,4-dihydropyridine, ayant une capacité de liaison à l'ADN. Nos résultats ont révélé que certains analogues de NAD + pourraient être utilisés par les PARPs pour la modification de l'ADN conduisant à la stabilisation des adduits MARylés et PARylés correspondants, en raison de leur résistance à l'activité d'hydrolyse des PARG. Ensemble, ces données mettent en évidence la pertinence physiologique et les résultats biologiques possibles de l’ADP-ribosylation de l’ADN catalysée par les protéines PARPs, tels que la fourniture d'une référence stable de l'emplacement d'une cassure du brin d'ADN sur une carte de chromatine, le recrutement de protéines de réparation de l'ADN et l'inhibition du mécanisme NHEJ toxiqueDNA-dependent poly(ADP-ribose) polymerases (PARPs) PARP1, PARP2 and PARP3 act as DNA break sensors signaling DNA damage. Upon detecting DNA damage, these PARPs use nicotine adenine dinucleotide as a substrate to synthesize a monomer or polymer of ADP-ribose (MAR or PAR, respectively) covalently attached to the acceptor residue of target proteins. Recently, it was demonstrated that PARP1–3 proteins can directly ADP-ribosylate DNA breaks by attaching MAR and PAR moieties to terminal phosphates. Nevertheless, little is still known about the mechanisms governing substrate recognition and specificity of PARP1, which accounts for most of cellular PARylation activity, as well, about proteins responsible for detection and removal of ADP-ribosylated DNA adducts and its role in multitude of cellular processes.In this study we provide a detailed characterization of PARP1 DNA substrate specificity and mechanisms of DNA PARylation. We showed that the 3′-terminal phosphate residue at double-strand DNA break ends served as a major acceptor site for PARP1-catalysed PARylation depending on the orientation and distance between DNA strand breaks in a single DNA molecule. Moreover, a preference for ADP-ribosylation of DNA molecules containing 3′-terminal phosphate over PARP1 auto-ADP-ribosylation was observed, and a model of DNA modification by PARP1 was proposed. Similar results were obtained with purified recombinant PARP1 and HeLa cell-free extracts. Thus, the biological effects of PARP-mediated ADP-ribosylation may strongly depend on the configuration of complex DNA strand breaks. Furthermore, we elaborated a new research technique to identify and validate proteins responsible for ADP-ribose-DNA adducts detection (“readers”) or removal (“erasers”). Our proteomic data revealed that MARylated DNA adducts selectively modulated DNA recognition of a large number of proteins involved in different cellular pathways. About 90 proteins including protein complexes were selected as potential MAR-DNA adduct readers. The role of DNA ADP-ribosylation in non-homologous end-joining (NHEJ) was partially characterized in an in vitro study. We demonstrated that ADP-ribosylation of DSB terminus can lead to inhibition of blunt DSB repair by canonical NHEJ if not removed by PARG glycohydrolase. Contrary, presence of a proximal nick with a stabilized apurinic/apyrimidinic site leads to increased NHEJ efficiency, apparently in ADP-ribosylation-independent manner. Finally we searched for novel PARP1, PARP2 and PARP3 inhibitors among derivatives of 1,4-dihydropyridine with DNA binding capacity. Our results revealed that some of NAD+ analogues analogs could be used by PARPs for DNA modification leading to stabilization of corresponding MARylated and PARylated adducts due to their PARG hydrolysis activity resistance. Taking together, these data highlight the physiological relevance and possible biological outcomes of PARP-catalyzed DNA-ADP-ribosylation such as providing a stable benchmark of the location of a DNA strand break on a chromatin map, recruitement of DNA repair proteins and inhibition of the toxic NHEJ
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Vernin, Emmanuelle. "Les bâtiments canoniaux du chapitre cathédral Notre-Dame du Puy-en-Velay : un centre "fortifié" de vie communautaire, intellectuelle et de spiritualité (Xe-début XVI siècles)." Lyon 2, 2003. http://theses.univ-lyon2.fr/documents/lyon2/2003/vernin_e.
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Les bâtiments canoniaux situés au nord de la cathédrale et organisés autour du cloître constituent un patrimoine architectural médiéval homogène, rare et composite. Leur période de construction est large et s'échelonne entre la fin du Xe siècle et le début du XVIe siècle, avec d'importants travaux aux XIe et XIIe siècles. Les restaurations successives jusqu'au XXe siècle ont préserver en partie ces édifices de destructions. Ce patrimoine architectural est l'un des lieux de vie quotidienne des religieux au Moyen Age. Au Puy, le chapitre cathédral se définit comme une "élite" intellectuelle et une seigneurie ecclésiastique. Dans ce but, il manifeste matériellement sur ce site sa puissance temporelle et spirituelle. Ceci est atteint par le choix d'implantation de son siège principal les bâtiments canoniaux sur un promontoire et aux partis architecturaux adoptés dans leur réalisation. Ainsi, l'Eglise de Puy semble avoir contribué à une création et une mise en place progressive d'une scénographie religieuse au cours du Moyen Age. L'organisation spatiale des édifices religieux les plus importants en rend compte. Cette scénographie était destinée à aider le pèlerin dans sa démarche.
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Maes, Bruno. "Pèlerinages nationaux et identité nationale en France, XVe-XVIIIe s. : Liesse, Saumur et Le Puy entre culture religieuse et culture politique." Reims, 1999. http://www.theses.fr/1999REIML005.
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Cette thèse analyse les rapports entre l'évolution de la culture religieuse des masses et l'évolution des formes de l'État en France, en prenant comme observatoire trois pèlerinages nationaux, au rôle politique important et au rayonnement lointain : quelles mutations de l'identité nationale reflète l'évolution de ces sanctuaires ? Dans un premier temps, aux XVe-XVIe s. , on assiste a leur élévation progressive a un rôle national, pour des raisons religieuses (leur fonction de sanctuaire à miracles leur donne un grand impact) et politiques (présence des grands, des rois, d'une frontière politique ou religieuse) ; ils entretiennent avec l'identité nationale des liens divers, que l'on retrouve à l'âge baroque : ils diffusent une image de la France alliée de la vierge, renforcent l'unité du pays autour du souverain et de la sainte française, permettent au centre politique de maitriser la périphérie en pèlerinant à la frontière, assurent à la monarchie la maitrise du temps en lui donnant une descendance, défendent l'identité catholique dans les régions protestantes, proposent par les légendaires des héros identificatoires à imiter. Un deuxième temps correspond à l'âge baroque (1600 / 1660-1680) ou une instrumentalisation systématique en est faite tant par l'Église que par l'État, et ils participent à la « confessionnalisation » de la France. Par ailleurs, ils diffusent les ferments d'une culture moderne (individualisme religieux, monde désenchanté et mœurs policées). Dans un troisième temps, pendant la seconde modernité, leur rôle politique décline, reflet d'une sécularisation précoce de l'identité nationale en France, phénomène concomitant de l'épanouissement religieux de liesse qui voit l'éclosion des fruits de la reforme catholique. Ainsi, l'évolution des pèlerinages nationaux comme créateurs, vecteurs ou miroirs d'identité nationale dans la France des XVe-XVIIIe s. Montre bien que l'histoire religieuse est un domaine fécond de l'histoire culturelle du politique car les liens que les hommes tissent avec le monde divin, avec la nature et entre eux sont imbriqués.
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Cabrero-Ravel, Laurence. "Notre-Dame du Port et la sculpture ornementale des églises romanes d'Auvergne, les chapitaux corinthiens et leurs dérivés : (fin XIe- XIIe siècle)." Besançon, 1996. http://www.theses.fr/1995BESA1042.
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Au sein de l'Auvergne romane, Notre-Dame du Port apparait centrale au point de vue architectural et sculptural pour un groupe de 33 édifices situés dans l'ancien diocèse de Clermont. Son architecture se caractérise par l'abondance de conservatismes. Sa sculpture ornementale, également tournée vers le passé, s'inscrit parmi les diverses renaissances que connut le corinthien a l'époque romane mais se distingue tant par la variété des compositions et des types végétaux que par son ouverture sur des motifs issus d'un autre répertoire décoratif. Une analyse systématique de l'architecture et de la sculpture met en évidence, au sein de cet ensemble d'édifices apparentés à Notre-Dame du Port, des sous familles faisant apparaitre des évolutions architecturales ou sculpturales qui, palliant la carence des sources textuelles, permettent de proposer des datations. Des comparaisons stylistiques avec des édifices non auvergnats et avec la sculpture de saint-marcellin de Chanteuges, dont on peut admettre que la reconstruction intervint peu après son rattachement à la Chaise-Dieu (1137) font situer la construction de Notre-Dame du Port, et d'un certain nombre d'églises affiliées, dans le premier tiers du XIIe siècle. Outre Chanteuges, d'autres édifices auvergnats apparaissent plus tardifs, notamment Brioude Chauriat et Riom.
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Croset, Amélie. "Identification et caractérisation des mécanismes d'action des molécules appats, les SiDNA, dans l'inhibition des voies de réparation des cassures simple-brin." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T018.
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La plupart des traitements anticancéreux, comme la chimiothérapie ou la radiothérapie, sont cytotoxiques et causent des dommages à l'ADN dans le but d’induire la mort des cellules tumorales. Cependant, l’efficacité d’activité de réparation de l'ADN des tumeurs entraine des résistances intrinsèques et acquises aux traitements. L'une des étapes précoces de la réparation de l’ADN est le recrutement de protéines au niveau du site de dommage. Ce recrutement est coordonné par une cascade de modifications et est contrôlé par des protéines senseurs telles que la protéine kinase ADN dépendante (DNA-PK) et / ou la poly (ADP- ribose) polymérase (PARP). Dans ce manuscrit, nous avons identifié et caractérisé le mécanisme d'action de petites molécules d'ADN (les siDNA), mimant des cassures double brin (appelé Dbait) ou simple brin (appelé Pbait), dans l’inhibition des voies de réparation des cassures simple brin (SSBR/BER). Nous démontrons que les molécules Dbait recrutent et activent à la fois PARP et DNA-PK, contrairement aux molécules Pbait qui ne recrutent que la PARP. L'étude comparative de ces deux molécules permet d'analyser les rôles respectifs des deux voies de signalisation: les deux molécules recrutent les protéines impliquées dans la voie de réparation des cassures simple brin (comme PARP, PCNA et XRCC1) et empêchent leurs recrutements aux niveaux des lésions chromosomiques. Les molécules Dbait inhibent par ailleurs le recrutement des protéines impliquées dans la voie de réparation des cassures double brin (NHEJ et HR). Pbait et Dbait désorganisent la réparation de l’ADN et sensibilisent les cellules tumorales aux traitements. L’inhibition de la réparation des cassures simple brin semble dépendre d’un piégeage des protéines directement sur les siDNA ou indirectement sur les polymères PAR. L’inhibition des voies de réparation des cassures double brin (DSB) semble par contre se faire de façon indirecte ; cette inhibition résulterait plutôt de la phosphorylation des protéines de réparation des DSB de part l’activation de DNA-PK. Les molécules Dbait et Pbait induisent un effet de létalité synthétique des cellules tumorales BRCA mutées. Cependant, la mutation BRCA semble être suffisante mais non nécessaire pour induire la sensibilité des cellules tumorales aux traitements Dbait. En effet, nous avons démontré que les molécules Dbait peuvent aussi sensibiliser les cellules ne présentant pas de mutation BRCA mais ayant toutefois une forte instabilité génétique. Nous avons trouvé une corrélation entre le niveau basal de protéines de réparation de l'ADN (ɣH2AX, PARP et PAR), le taux basal de cassures à l’ADN, la présence de micronoyaux (MN) et la sensibilité des cellules tumorales au traitement Dbait. Nous avons émis l’hypothèse que cette instabilité génétique, déterminé par la quantification de MN dans des biopsies tumorales, pourrait être un biomarqueur prédictif de l’effet du Dbait, non seulement dans les cancers du sein, mais aussi dans les glioblastomes, les mélanomes, les mélanomes uvéaux et les cancers du côlonMost conventional cancer treatments, such as chemotherapy or radiotherapy, are cytotoxic and cause DNA damages in the tumoral treated cells, which ultimately lead to their death. However, several intrinsic and acquired resistances of tumors to these treatments are due to the tumor efficient DNA repair activities. One of the major early steps of DNA repair is the recruitment of repair proteins at the damage site and this is coordinated by a cascade of modifications controlled by sensor proteins such as DNA-dependent protein kinase (DNA-PK) and/or poly (ADP-ribose) polymerase (PARP). In this manuscript, we identify and characterize the mechanism of action of short interfering DNA molecules (siDNA), mimicking double-strand breaks (called Dbait) or single-strand breaks (called Pbait) in Single Strand Break Repair pathway (SSBR/BER) inhibition. We demonstrate that Dbait bound and induced both PARP and DNA-PK activities, whereas Pbait acts only on PARP. The comparative study of the two molecules allows analysis of the respective roles of the two signaling pathways: both molecules recruit proteins involved in single-strand break repair (such as PARP, XRCC1 and PCNA) and prevent their recruitment at chromosomal damage. Dbait, but not Pbait, also inhibits recruitment of proteins involved in double-strand break (DSB) repair. By these ways, Pbait and Dbait disorganized DNA repair, thereby sensitizing cells to treatments. SSB repair inhibition depends upon a direct trapping of the main proteins on both molecules and an indirect trapping in PAR polymers. DSB repair inhibition may be indirect, resulting from the phosphorylation of DSB repair proteins by activated DNA-PK. The DNA repair inhibition by both molecules is confirmed by their synthetic lethality with BRCA mutations tumoral cell lines. However, BRCA mutation could be sufficient but not necessary to induce breast cancer cell lines and tumors sensitivity to Dbait treatment. In fact, we demonstrate that Dbait molecules could also have a stand-alone effect in BRCA wild type cells with a high genetic instability. We found a correlation between DNA repair proteins basal level (ɣH2AX, PARP and PAR), DNA break basal level, presence of micronucleus (MN) and tumoral cell lines sensitivity to Dbait treatment. We hypothesis that this genetic instability, determined by MN in tumor biopsies, could be a predictive biomarker of Dbait stand-alone effect, not only in breast cancer treatment, but also in glioblastoma, melanoma, uveal melanoma and colon cancer treatment
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Burns, Kristi Lee. "An exploration of biochemistry including biotechnology, structural characterization, drug design, and chromatographic analyses." Diss., Atlanta, Ga. : Georgia Institute of Technology, 2006. http://hdl.handle.net/1853/29593.
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Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2007.Committee Chair: Sheldon W. May ; Committee Members: Donald F. Doyle, Leslie T. Gelbaum, Stanley H. Pollock, and James Powers. Part of the SMARTech Electronic Thesis and Dissertation Collection.
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永正, 邵., and Yongzheng Shao. "Study on the effects of matrix properties on the mechanical properties of carbon fiber reinforced plastic composites." Thesis, https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB12902982/?lang=0, 2015. https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB12902982/?lang=0.
Full textAbstract:
It was found that a significant improvement of mechanical properties of CFRPs can be achieved by the adjustment of the matrix properties such as toughness and CF/matrix adhesion via the chemical modification, as well as the physical modification by a small amount of cheap and environment-friendly nano fibers. Based on investigation of fracture mechanisms at macro/micro scale, the effects of matrix properties and nano fiber on the mechanical properties of CFRP have been discussed. Subsequently, the relationship has been characterized by a numerical model to show how to modulate the parameters of the matrix properties to achieve excellent fatigue properties of CFRP.博士(工学)
Doctor of Philosophy in Engineering
同志社大学
Doshisha University
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Ben, Hafsia Khaoula. "Identification des micro-mécanismes de déformation du PET amorphe et semi-cristallin in situ au cours d’un essai mécanique." Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0081/document.
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Selon leur formulation et leur mise en forme et grâce à leur complexité microstructurale induite, les polymères thermoplastiques bénéficient d’une grande diversité de propriétés thermomécaniques. Cependant, l’évolution de la microstructure de ces matériaux au cours de leur utilisation reste difficile à identifier. Afin de mieux comprendre les modifications microstructurales ayant lieu au cours de sollicitations thermomécaniques, différentes techniques non destructives de caractérisation en temps réel et in situ ont été développées. Dans ce contexte, un Poly (Ethylène Téréphtalate) (PET) amorphe et semi-cristallin a été étudié afin de mettre en évidence l’effet de la microstructure sur les propriétés macroscopiques du matériau. Pour ce faire, plusieurs couplages de techniques expérimentales de caractérisation ont été mis en œuvre tels que la spectroscopie Raman et la diffraction/diffusion des rayons X couplées au système de VidéoTraction™ ou la spectroscopie Raman couplée à la calorimétrie différentielle à balayage (DSC) pour une caractérisation des micromécanismes de déformation et du comportement thermique du matériau respectivement. Le suivi de différentes bandes vibrationnelles judicieusement identifiées a permis d’établir un nouveau critère robuste et capable de mesurer avec exactitude le taux de cristallinité du matériau ou de remonter aux températures caractéristiques de sa morphologie (Tg, Tc, Tcc, Tf) grâce aux informations extraites d’un spectre Raman. De plus, un système de caractérisation relaxationnelle par un couplage de la spectroscopie diélectrique dynamique avec un essai de traction a été utilisé afin de mettre en évidence l’effet de la mobilité moléculaire sur la déformation élasto-visco-plastique du PET. D’un point de vue mécanique, les principaux micromécanismes de déformation ont été étudiés en temps réel pendant un essai de traction à différentes températures et vitesses de déformation vraies constantes : l’orientation macromoléculaire, l’endommagement volumique, le développement de mésophase et la cristallisation induite sous contrainte, ont été observés et quantifiés in situ en utilisant les couplages précédents au synchrotron Petra III de Hambourg et au synchrotron Elettra de Trieste. En parallèle, une étude de la mobilité moléculaire (paramètre déterminant à la prédominance de tel ou tel micromécanisme de déformation) a été menée via des analyses relaxationnelles réalisées au cours de la déformation du matériau. En complément, des expériences en temps réel, des études post mortem par les techniques précédemment citées et par radiographie X, microscopie électronique à balayage et tomographie X ont été réalisées afin d’apprécier l’influence de la relaxation mécanique du PETAccording to their formulations and forming processes and thanks to the complexity of their induced microstructure, thermoplastic polymers show a wide range of thermomechanical properties. However, the identification of the evolution of the microstructure of these materials during their use remains difficult. To better understand the microstructural changes occurring during thermomechanical loadings, various in situ and non-destructive techniques of characterization have been used. In this context, a Poly (Ethylene Terephthalate) (PET) amorphous and semi-crystalline was studied in order to highlight the effect of the microstructure on the macroscopic properties of the material. This way, different coupling systems combining several experimental characterization techniques have been implemented such as Raman spectroscopy and X-rays diffraction/scattering coupled to the VidéoTraction™ system or Raman spectroscopy coupled with differential scanning calorimetry (DSC) for the characterization of the deformation micro-mechanisms and the thermal behavior of the material respectively. Monitoring specific vibrational bands thoroughly identified allowed the establishment of a new robust criterion which enables to accurately measure the crystallinity ratio of the material and the identification of the characteristic temperatures of its morphology (Tg, Tc, Tcc, Tm). In addition, a relaxational characterization system by coupling dynamic dielectric spectroscopy to a tensile test has been used in order to highlight the effect of molecular mobility on the elasto-visco-plastic deformation of PET. From a mechanical point of view, the main deformation micro-mechanisms have been studied in real time during a tensile test at different temperatures and constant true strain rates: macromolecular orientation, volume damage, development of mesophase and strain induced crystallization were observed and quantified in situ using the coupled characterization technics presented previously at Petra III (Hambourg) and Elettra (Trieste) synchrotrons. In parallel, a study of the molecular mobility (a determining parameter for the predominance of one deformation micromechanism to another) was conducted via relaxational analysis performed during the deformation of the material. In addition to in situ experiments, post mortem analysis by the previously mentioned technics and by X radiography, scanning electron microscopy and X tomography were performed to assess the influence of the mechanical relaxation of the polymer
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Muriithi, Paul Mutuanyingi. "A case for memory enhancement : ethical, social, legal, and policy implications for enhancing the memory." Thesis, University of Manchester, 2014. https://www.research.manchester.ac.uk/portal/en/theses/a-case-for-memory-enhancement-ethical-social-legal-and-policy-implications-for-enhancing-the-memory(bf11d09d-6326-49d2-8ef3-a40340471acf).html.
Full textAbstract:
The desire to enhance and make ourselves better is not a new one and it has continued to intrigue throughout the ages. Individuals have continued to seek ways to improve and enhance their well-being for example through nutrition, physical exercise, education and so on. Crucial to this improvement of their well-being is improving their ability to remember. Hence, people interested in improving their well-being, are often interested in memory as well. The rationale being that memory is crucial to our well-being. The desire to improve one’s memory then is almost certainly as old as the desire to improve one’s well-being. Traditionally, people have used different means in an attempt to enhance their memories: for example in learning through storytelling, studying, and apprenticeship. In remembering through practices like mnemonics, repetition, singing, and drumming. In retaining, storing and consolidating memories through nutrition and stimulants like coffee to help keep awake; and by external aids like notepads and computers. In forgetting through rituals and rites. Recent scientific advances in biotechnology, nanotechnology, molecular biology, neuroscience, and information technologies, present a wide variety of technologies to enhance many different aspects of human functioning. Thus, some commentators have identified human enhancement as central and one of the most fascinating subject in bioethics in the last two decades. Within, this period, most of the commentators have addressed the Ethical, Social, Legal and Policy (ESLP) issues in human enhancements as a whole as opposed to specific enhancements. However, this is problematic and recently various commentators have found this to be deficient and called for a contextualized case-by-case analysis to human enhancements for example genetic enhancement, moral enhancement, and in my case memory enhancement (ME). The rationale being that the reasons for accepting/rejecting a particular enhancement vary depending on the enhancement itself. Given this enormous variation, moral and legal generalizations about all enhancement processes and technologies are unwise and they should instead be evaluated individually. Taking this as a point of departure, this research will focus specifically on making a case for ME and in doing so assessing the ESLP implications arising from ME. My analysis will draw on the already existing literature for and against enhancement, especially in part two of this thesis; but it will be novel in providing a much more in-depth analysis of ME. From this perspective, I will contribute to the ME debate through two reviews that address the question how we enhance the memory, and through four original papers discussed in part three of this thesis, where I examine and evaluate critically specific ESLP issues that arise with the use of ME. In the conclusion, I will amalgamate all my contribution to the ME debate and suggest the future direction for the ME debate.
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Silva, Carolina Furtado Pereira da. "Damage and fracture in advanced composite laminates: thin-ply and nanoengineered composites." Doctoral thesis, 2020. https://hdl.handle.net/10216/125860.
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Vieira, Tiago Vaz Maia. "Analysis of ply damage using computational micro-mechanics: transverse shear failure mechanisms." Dissertação, 2020. https://hdl.handle.net/10216/129669.
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Vieira, Tiago Vaz Maia. "Analysis of ply damage using computational micro-mechanics: transverse shear failure mechanisms." Master's thesis, 2020. https://hdl.handle.net/10216/129669.
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Wafai, Husam. "Effects of matrix properties on microscale damage in thermoplastic laminates under quasi-static and impact loading." Diss., 2018. http://hdl.handle.net/10754/627434.
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Thermoplastics reinforced with continuous fibers are very promising building materials
for the auto industry and consumer electronics to reduce the weight of vehicles and portable
devices, and to deliver a high impact tolerance at the same time. Polypropylene is an abundant
thermoplastic, and its glass fibers composites make a valuable solution that is suitable
for mass production. But the adoption of such composites requires a deep understanding
of their mechanical behavior under the relevant loading conditions.
In this Ph.D. work, we aim to understand the damage process in continuous glass fiberreinforced
polypropylene in detail. We will focus in particular on developing an approach
for microscale observation of damage during the out-of-plane loading process and will use
these observations for both qualitative and quantitative evaluation of the composite. We
will apply our approach to two kinds of polypropylene composites, one of them is specially
designed to withstand impact. The comparison between the two types of composites at slow
and fast loading cases will shed some light on the effect of the polymer properties on the
behavior of composites under out-of-plane loading.
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Traudes, Daniel. "In Situ Tomography of Microcracking in Cross Ply Carbon Fiber Composites with Pre-existing Debonding Damage." Thesis, 2012. http://hdl.handle.net/10754/235331.
Full textAbstract:
Carbon fiber based composites are an essential material in weight-critical applications
such as in the aerospace industry. However, these materials are susceptible to
damage such as matrix microcracking and fiber/matrix debonding (diffuse damage),
which occurs at stresses much lower than the failure stress.
A T700/M21 [0/90]s laminate was tensile loaded to introduce diffuse damage and
prepared for a study on the initiation of transverse microcracks. The material was
tensile loaded in a [+45/-45]s orientation to induce diffuse damage. A diffuse damage
indicator was developed by measuring the decrease in shear stiffness. Samples with
diffuse damage levels of 0, 0.05, 0.10, 0.15, 0.20, and 0.25 were prepared to be tensile
tested in a [0/90]s orientation to induce microcracks.
A successful development of the microcracking test procedure was performed. The
edge of the material was studied with optical microscopy and x-ray to establish the
structure of the fiber bundle geometry when undamaged. A sample containing microcracks
was treated with diiodomethane dye penetrant, which successfully highlighted
microcracks during x-ray imaging. The application time was not sufficient to produce consistent x-ray images over time, so a 45 minute soak time was recommended
instead. The same damaged sample was subjected to a tomographic scan without
a dye penetrant and while unloaded. Transverse microcracks were successfully identified from the data, although the results were not clean enough and likely omitted
some smaller microcracks. Results are expected to be cleaner if performed during
tensile testing.
Future tensile testing will quantify the induced crack density of samples containing
various degrees of initial diffuse damage, either using x-rays with a dye penetrant or
using x-ray microtomography.
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Mustafa, Ghulam. "High fidelity micromechanics-based statistical analysis of composite material properties." Thesis, 2016. http://hdl.handle.net/1828/7100.
Full textAbstract:
Composite materials are being widely used in light weight structural applications due to their high specific stiffness and strength properties. However, predicting their mechanical behaviour accurately is a difficult task because of the complicated nature of these heterogeneous materials. This behaviour is not easily modeled with most of existing macro mechanics based models. Designers compensate for the model unknowns in failure predictions by generating overly conservative designs with relatively simple ply stacking sequences, thereby mitigating many of the benefits promised by composites.
The research presented in this dissertation was undertaken with the primary goal of providing efficient methodologies for use in the design of composite structures considering inherent material variability and model shortcomings. A micromechanics based methodology is proposed to simulate stiffness, strength, and fatigue behaviour of composites. The computational micromechanics framework is based on the properties of the constituents of composite materials: the fiber, matrix and fiber/matrix interface. This model helps the designer to understand in-depth the failure modes in these materials and design efficient structures utilizing arbitrary layups with a reduced requirement for supporting experimental testing. The only limiting factor in using a micromechanics model is the challenge in obtaining the constituent properties. The overall novelty of this dissertation is to calibrate these constituent properties by integrating the micromechanics approach with a Bayesian statistical model.
The early research explored the probabilistic aspects of the constituent properties to calculate the stiffness characteristics of a unidirectional lamina. Then these stochastic stiffness properties were considered as an input to analyze the wing box of a wind turbine blade. Results of this study gave a gateway to map constituent uncertainties to the top-level structure. Next, a stochastic first ply failure load method was developed based on micromechanics and Bayesian inference. Finally, probabilistic SN curves of composite materials were calculated after fatigue model parameter calibration using Bayesian inference.
Throughout this research, extensive experimental data sets from literature have been used to calibrate and evaluate the proposed models. The micromechanics based probabilistic framework formulated here is quite general, and applied on the specific application of a wind turbine blade. The procedure may be easily generalized to deal with other structural applications such as storage tanks, pressure vessels, civil structural cladding, unmanned air vehicles, automotive bodies, etc. which can be explored in future work.Graduate
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enginer315@gmail.com