An implantable hearing aid device is being developed by a project group which is part of an EU initiative. This device contains a diaphragm consisting of a submicron thick freestanding titanium film, which should be free of internal stresses. Stress is the force exerted per unit cross-sectional area of the film and it can impair the functionality and performance of the device. The stress that evolves in a thin film during deposition at a substrate is compressive or/and tensile and affects the bending that occurs of the substrate due to the lateral force applied to the substrate by the stressed film. The goal of this diploma work was to contribute to the understanding of in situ stress evolution in a micron thick titanium film and thereby by tuning different physical parameters to obtain minimal residual stress in the films after growth. Titanium films were deposited on silicon sistrates using DC magnetron sputtering. The stress in the material varied, by tuning different physical parameters such as working pressure, power, distance between magnetron and the sample and substrate bias. For this thesis, firstly two different series were done; one where the changing parameter was the distance between the sample and the magnetron and one where it was the working pressure. Later a last series were done to see what effect the bias has on the stress. A multi-beam optical sensor system (MOS) was used to measure the stress in real-time during deposition. X-ray diffraction (XRD) was later used to make post-deposition stress measurements to verify the stress obtained from the MOS. However, the MOS shows the stress evolution in real time and XRD shows a ’final’ average value that can be compared with the stress obtained from MOS-data when the deposition is finished. The results showed that the stress goes from compressive to tensile as the working pressure and the distance between the magnetron and the sample increases. There are other factors, such as the temperature/heating in the main chamber, base pressure of the main chamber, cleaning of the sample and also where the argon gas is let in to the process chamber (in this project called the main chamber (MC)), that influences the results. This will in turn influence the repeatability of the data/measurements, since these effects can affect the process of nucleation and coalescence. The stress evolution can change if a bias is applied during the initial stage of the deposition process when the film has still not grown thick. This is could be due to the bias not having much of an impact on the stress evolution when the film is thicker and thereby more porous.

Ganglion cell death in glaucoma is caused by a variety of insults that include ischemia, insufficient neurotrophic support and oxidative stress. Experimental studies were therefore conducted on cell cultures to determine how serum deprivation (to mimic insufficient neurotrophic support) or oxidative glutamate toxicity (GB), cause oxidative stress and induce retinal cell death. Moreover, studies were carried out to deduce whether selected sulphur containing compounds can blunt any negative influences to cells in culture and/or a defined ischaemic insult to the rat retina in situ, as this might suggest their use for the treatment of glaucoma. Serum deprivation and GB caused generation of reactive oxygen species (ROS) and apoptosis-like death to transformed retinal ganglion cells (RGC-5 cells). RGC-5 cells were more susceptible to the detrimental effects of GB than serum deprivation. RGC-5 cells subjected to serum deprivation appear to die by mechanisms that resemble classical apoptosis more closely than that caused by GB and the phase between the maximal generation of ROS and cell death were different. Cell death caused by serum deprivation was caspase-dependent but this was not the case for GB. Moreover, of the two sulphur compounds sulbutiamine and N-acetyl cysteine (NAC), sulbutiamine blunts the effect of serum deprivation more effectively. In addition, the pan caspase inhibitor z-VAD-fmk attenuated the negative effect of serum deprivation to RGC-5 cells while the necroptosis inhibitor (necrostsatin-1) counteracted solely the insult of GB. The sulphur containing compounds, ACS1 and ACS 67 which release hydrogen sulphide (H2S) slowly and NAC (a pro-cysteine GSH precursor) attenuated GB-induced cell death of RGC-5 cells. In contrast, sulbutiamine (a lipophilic thiolic thiamine derivative) was particularly effective in protecting RGC-5 cells from an insult of serum deprivation. Moreover, all of the sulphur compounds directly sequestered different types of ROS but with varying efficiency. Common features by which all tested sulphur containing agents seem to elicit a mode of action include the stimulation of GSH and the antioxidant enzyme glutathione-S-transferase (GST) as well as to scavenge excess free radicals. Moreover, the slow release of H₂S from the ACS compounds appears to protect cells from oxidative stress through increasing the level of GSH, modulation of the cystine uptake transporter xCT, stimulation of the oxidative stress related transcription factor Nrf2 and the stimulation of pro-survival signalling pathways. The slow releasing H₂S sulphur compound ACS67 also counteracts a number of detrimental influences to the rat retina in situ because of ischemia/reperfusion that includes damage to their ganglion cells. This suggests that such sulphur compounds might find a use in the treatment of glaucoma where ischemia probably plays a part in the disease process.

Ce travail de thèse a pour objet de contribuer à la compréhension de la déformation des assemblages combustibles REP équipés de composants en alliages de zirconium (Zy-4 ou M5). En particulier, nous nous sommes intéressés à l’accélération de croissance, corrélée à l’apparition d’un type de défaut d’irradiation : les boucles à composante <c>. Des irradiations aux particules chargées nous ont permis de reproduire ces évolutions microstructurales et d’étudier leur représentativité. La morphologie du dommage primaire n’a ainsi que peu d’impact sur la microstructure de boucles <c> tandis que le taux de création de dommage (tout comme la température) semble jouer un rôle majeur. Par ailleurs, la dose seuil pour la nucléation des boucles <c> apparaît étroitement liée à la cinétique de croissance des amas lacunaires et des germes de boucles. Cette cinétique peut être influencée par le taux de création de dommage, les éléments d’alliages, mais également la contrainte ou la présence d’hydrogène (introduit dans le matériau lors de l’oxydation en réacteur). Ce travail a ainsi exploré de manière approfondie l’effet d’une contrainte appliquée dans les domaines d’élasticité et de plasticité ainsi que l’impact de l’hydrogène absorbé sur la nucléation et la croissance des boucles <c>. Conformément au mécanisme SIPA proposé dans la littérature, nous avons observé un effet de la contrainte sur les boucles <c>. Par ailleurs, cette étude met en évidence que l’hydrogène en solution et / ou sous forme d’hydrures influence significativement la nucléation et la croissance des boucles <c>. / The aim of this PhD work is to have a better understanding of axial elongation of the PWR fuel assemblies manufactured in zirconium alloys (Zy-4 or M5). More specifically, we focused on the growth acceleration of these assemblies, clearly correlated to the nucleation of specific irradiation defects: the c-loops. Irradiations by charged particles were performed in order to reproduce the microstructure evolution and to study its representativeness. Thus, primary damage morphology has no impact on the c-loop microstructures where as the damage creation rate (like the temperature) seems to play a major role. Moreover, the nucleation dose for c-loops appears clearly correlated to the nuclei and vacancy clusters growth kinetics. This kinetics could be influenced by the damage creation rate, the alloying elements, but also by an applied stress or the hydrogen content (which can be introduced during oxidation in reactor). Thus, this work has explored the effect of an applied stress (in the elasticity or plasticity domain) and the impact of the hydrogen pick-up on the nucleation and growth of c-loops. In accordance with the SIPA mechanism described in the literature, we observed an effect of the applied stress on the c-loop microstructures. Moreover, this study clearly shows an impact of hydrogen in solid solution and as precipitated hydrides on the nucleation and growth of c-loops.

Introduction: Takotsubo cardiomyopathy is an apical ballooning syndrome, which can be triggeredby stress. Only few case reports describe the onset of Takotsubo as a complication of neurosurgery procedures. Clinical presentation: A case of a 53 year-old female with a spinal neurinoma and surgery-associated Takotsubo cardiomyopathy is demonstrated. The patient developed typical signs of a myocardial infarction with circulation depression and ST elevation, but normal cardiac enzymes at the end of surgery. Cardiac catheterization and levocardiography confirmed the absence of any critical coronary disease but the presence of a typical apical ballooning and midventricular hypokinesis. The patient recovered completely under supportive conservative and cardiological therapy, showing regular left ventricular pumpfunction. Conclusion: Interventions in neurosurgery and perioperative care should be kept as stress free as possible. Due to the possibility of neurogenic mechanisms related to cardiomyopathy, Takotsubo cardiomyopathy as an entity of stress-induced complications should be taken into consideration.

This research investigates wave propagation in an elastic half-space with a quadratic nonlinearity in its stress-strain relationship. Different boundary conditions on the surface are considered that result in both one- and two-dimensional wave propagation problems. The goal of the research is to examine the generation of second-order frequency effects and static effects which may be used to determine the nonlinearity present in the material. This is accomplished by extracting the amplitudes of those effects in the frequency domain and analyzing their dependency on the third-order elastic constants (TOEC). For the one-dimensional problems, both analytical approximate solutions as well as numerical simulations are presented. For the two-dimensional problems, numerical solutions are presented whose dependency on the material's nonlinearity is compared to the one-dimensional problems. The numerical solutions are obtained by first formulating the problem as a hyperbolic system of conservation laws, which is then solved numerically using a semi-discrete central scheme. The numerical method is implemented using the package CentPack. In the one-dimensional cases, it is shown that the analytical and numerical solutions are in good agreement with each other, as well as how different boundary conditions may be used to measure the TOEC. In the two-dimensional cases, it is shown that there exist comparable dependencies of the second-order frequency effects and static effects on the TOEC. Finally, it is analytically and numerically investigated how multiple reflections in a plate can be used to simplify measurements of the material nonlinearity in an experiment.

Introduction: Takotsubo cardiomyopathy is an apical ballooning syndrome, which can be triggeredby stress. Only few case reports describe the onset of Takotsubo as a complication of neurosurgery procedures. Clinical presentation: A case of a 53 year-old female with a spinal neurinoma and surgery-associated Takotsubo cardiomyopathy is demonstrated. The patient developed typical signs of a myocardial infarction with circulation depression and ST elevation, but normal cardiac enzymes at the end of surgery. Cardiac catheterization and levocardiography confirmed the absence of any critical coronary disease but the presence of a typical apical ballooning and midventricular hypokinesis. The patient recovered completely under supportive conservative and cardiological therapy, showing regular left ventricular pumpfunction. Conclusion: Interventions in neurosurgery and perioperative care should be kept as stress free as possible. Due to the possibility of neurogenic mechanisms related to cardiomyopathy, Takotsubo cardiomyopathy as an entity of stress-induced complications should be taken into consideration.