Einfluss von oxidativem Stress auf die DNA-Reparatur in Säugerzellen

Gegenstand dieser Arbeit war es, das Zusammenspiel zwischen DNA-Reparatur und zellulärem anitoxidativen Abwehrsystem in Melanomzellen und gesunden Hautfibroblasten näher zu untersuchen. Dabei konnte gezeigt werden, dass die dominierenden DNA-Läsionen im Falle einer Bestrahlung mit sichtbarem Licht (400 – 800 nm) Fpg-sensitive Läsionen, zu denen die Basenmodifikation 7,8-Dihydro-8-oxoguanin (8-oxoG) gehört, und im Falle der UVA-Bestrahlung Cyclobutan-Pyrimidindimere (CPDs) sind. Sowohl Melanomzellen als auch Hautfibroblasten waren problemlos in der Lage, die durch sichtbares Licht und UVA-Strahlung induzierten oxidativen DNA-Modifikationen zu reparieren. Jedoch reagierten Melanomzellen in einer adaptiven Antwort mit einer Erhöhung ihres Glutathion-Gehalts auf ein Maximum (nach circa 10 - 14 h) nach Bestrahlung mit sichtbarem Licht, wohingegen die Hautfibroblasten einen massiven Einbruch direkt nach Bestrahlung und eine extrem lange Erholungsphase über 48 h aufzuweisen hatten. Die darauffolgende Untersuchung der DNA-Reparaturkapazität der Zellen unter Bedingungen von oxidativem Stress mit vorangegangener Depletion intrazellulären Glutathions zeigten eine dramatische, nahezu vollständige Hemmung der Reparatur durch UVA- bzw. Sonnenlicht-induzierter Fpg-sensitiver DNA-Modifikationen (8-oxoG) - sowohl in Melanomzellen als auch in Hautfibroblasten. Dieser Effekt ließ sich durch den Zusatz von Dithiothreitol (DTT), nach erfolgter Bestrahlung der Glutathion-depletierten Zellen, wieder komplett revertieren. Diese Ergebnisse weisen darauf hin, dass an der Reparatur ein redoxempfindliches Protein oder zellulärer Cofaktor beteiligt sein muß. Zudem konnte durch Untersuchungen der Nukleotidexzisionsreparatur (NER) und der Einzelstrangbruchreparatur nach dem gleichen Versuchsdesign gezeigt werden, dass es sich hierbei sehr wahrscheinlich um einen für die Basenexzisionsreparatur (BER) von 7,8-dihydro-8-oxo-guanine (8-oxoG) exklusiven Effekt handelte. Zwei der wichtigsten Reparaturproteine der BER, nämlich hOGG1 und APE1, wurden anschließend auf ihre Funktionsfähigkeit hin untersucht, da es naheliegend war, dass der Reparaturhemmung ein Funktionsverlust eines dieser beiden Enzyme zugrunde liegen könnte. Im Falle des APE1-Proteins konnte dies ausgeschlossen werden, da mit Hilfe der Alkalischen Elution die volle Funktionsfähigkeit für die Reparatur von AP-Läsionen nachgewiesen werden konnte. Interessanterweise zeigte aber das hOGG1-Protein eine zwischen der dritten und vierten Stunde nach Bestrahlung Glutathion-depletierter Zellen stark abfallende Aktivität der 8-oxoG-Glykosylasefunktion. Die Western-Blot-Analyse ergab allerdings keinen Hinweis auf eine Proteinoxidation von hOGG1. Möglicherweise wird nicht hOGG1 selbst, wohl aber ein anderes, für eine konzertierte Abfolge der einzelnen Reparaturschritte entscheidend notwendiges Protein innerhalb der Zelle durch ROS leicht oxidiert. In jedem Fall bleibt festzustellen, dass Glutathion eine wichtige Aufgabe hinsichtlich einer voll funktionsfähigen Basenexzisionreparatur zuzukommen scheint. Die Ergebnisse unterstreichen die mögliche Bedeutung von oxidativem Stress für die Entstehung von Krebs durch Sonnenlicht, insbesondere durch UVA, da die durch die Strahlung (und eventuell auftretende Entzündung) gebildeten ROS nicht nur DNA-Schäden induzieren, sondern auch ihre Reparatur verhindern können.

Finite element modeling of the cement-bone interface beneath the tibial tray of a total knee arthroplasty: Study of the stress shielding effect (modellazione agli elementi finiti dell'interfaccia cemento-osso sotto il piatto tibiale di protesi totale di ginocchio: Analisi dello stress shielding)

The goal of this thesis was the study of the cement-bone interface in the tibial component of a cemented total knee prosthesis. One of the things you can see in specimens after in vivo service is that resorption of bone occurs in the interdigitated region between bone and cement. A stress shielding effect was investigated as a cause to explain bone resorption. Stress shielding occurs when bone is loaded less than physiological and therefore it starts remodeling according to the new loading conditions. µCT images were used to obtain 3D models of the bone and cement structure and a Finite Element Analysis was used to simulate different kind of loads. Resorption was also simulated by performing erosion operations in the interdigitated bone region. Finally, 4 models were simulated: bone (trabecular), bone with cement, and two models of bone with cement after progressive erosions of the bone. Compression, tension and shear test were simulated for each model in displacement-control until 2% of strain. The results show how the principal strain and Von Mises stress decrease after adding the cement on the structure and after the erosion operations. These results show that a stress shielding effect does occur and rises after resorption starts.

Stress and Strain Adaptation in Load-Dependent Remodeling of the Embryonic Left Ventricle

Altered pressure in the developing left ventricle (LV) results in altered morphology and tissue material properties. Mechanical stress and strain may play a role in the regulating process. This study showed that confocal microscopy, three-dimensional reconstruction, and finite element analysis can provide a detailed model of stress and strain in the trabeculated embryonic heart. The method was used to test the hypothesis that end-diastolic strains are normalized after altered loading of the LV during the stages of trabecular compaction and chamber formation. Stage-29 chick LVs subjected to pressure overload and underload at stage 21 were reconstructed with full trabecular morphology from confocal images and analyzed with finite element techniques. Measured material properties and intraventricular pressures were specified in the models. The results show volume-weighted end-diastolic von Mises stress and strain averaging 50–82% higher in the trabecular tissue than in the compact wall. The volume-weighted-average stresses for the entire LV were 115, 64, and 147Pa in control, underloaded, and overloaded models, while strains were 11, 7, and 4%; thus, neither was normalized in a volume-weighted sense. Localized epicardial strains at mid-longitudinal level were similar among the three groups and to strains measured from high-resolution ultrasound images. Sensitivity analysis showed changes in material properties are more significant than changes in geometry in the overloaded strain adaptation, although resulting stress was similar in both types of adaptation. These results emphasize the importance of appropriate metrics and the role of trabecular tissue in evaluating the evolution of stress and strain in relation to pressure-induced adaptation.

The von Mises-Fisher distribution of the first exit point from the hypersphere of the drifted Brownian motion and the density of the first exit time

A characterization is provided for the von Mises–Fisher random variable, in terms of first exit point from the unit hypersphere of the drifted Wiener process. Laplace transform formulae for the first exit time from the unit hypersphere of the drifted Wiener process are provided. Post representations in terms of Bell polynomials are provided for the densities of the first exit times from the circle and from the sphere.

An efficient simulation algorithm for the generalized von Mises distribution of order two

In this article we propose an exact efficient simulation algorithm for the generalized von Mises circular distribution of order two. It is an acceptance-rejection algorithm with a piecewise linear envelope based on the local extrema and the inflexion points of the generalized von Mises density of order two. We show that these points can be obtained from the roots of polynomials and degrees four and eight, which can be easily obtained by the methods of Ferrari and Weierstrass. A comparative study with the von Neumann acceptance-rejection, with the ratio-of-uniforms and with a Markov chain Monte Carlo algorithms shows that this new method is generally the most efficient.

Helene von Mises

B. Samuel

Arthur Edler von Mises [Illustration] : geb. 1854 - gest. 1903

Scan von Monochrom-Mikroform

Univariate and bivariate truncated von Mises distributions

In this article we study the univariate and bivariate truncated von Mises distribution, as a generalization of the von Mises distribution (\cite{jupp1989}), (\cite{mardia2000directional}). This implies the addition of two or four new truncation parameters in the univariate and, bivariate cases, respectively. The results include the definition, properties of the distribution and maximum likelihood estimators for the univariate and bivariate cases. Additionally, the analysis of the bivariate case shows how the conditional distribution is a truncated von Mises distribution, whereas the marginal distribution that generalizes the distribution introduced in \cite{repe}. From the viewpoint of applications, we test the distribution with simulated data, as well as with data regarding leaf inclination angles (\cite{safari}) and dihedral angles in protein chains (\cite{prote}). This research aims to assert this probability distribution as a potential option for modelling or simulating any kind of phenomena where circular distributions are applicable.\par

Das Büchlein vom Leben nach dem Tode, von Mises.

Mode of access: Internet.

Exponentially decaying pressure pulse moving with superseismic velocity on the surface of a half space of Von Mises elastoplastic material

Mode of access: Internet.

Influence of implant-abutment angulations and crown material on stress distribution on central incisor: a 3D FEA

Aim: To investigate the effect of implant-abutment angulation and crown material on stress distribution of central incisors. Finite element method was used to simulate the clinical situation of a maxillary right central incisor restored by two different implant-abutment angulations, 15° and 25°, using two different crown materials (IPS E-Max CAD and zirconia). Methods: Two 3D finite element models were specially prepared for this research simulating the abutment angulations. Commercial engineering CAD/CAM package was used to model crown, implant abutment complex and bone (cortical and spongy) in 3D. Linear static analysis was performed by applying a 178 N oblique load. The obtained results were compared with former experimental results. Results: Implant Von Mises stress level was negligibly changed with increasing abutment angulation. The abutment with higher angulation is mechanically weaker and expected to fail at lower loading in comparison with the steeper one. Similarly, screw used with abutment angulation of 25° will fail at lower (about one-third) load value the failure load of similar screw used with abutment angulated by 15°. Conclusions: Bone (cortical and spongy) is insensitive to crown material. Increasing abutment angulation from 15° to 25°, increases stress on cortical bone by about 20% and reduces it by about 12% on spongy bone. Crown fracture resistance is dramatically reduced by increasing abutment angulation. Zirconia crown showed better performance than E-Max one.

Advanced numerical study of impact forces on railway sleepers under wheel flat

Wheel-rail interaction is one of the most important research topics in railway engineering. It includes track vibration, track impact response and safety of the track. Track structure failures caused by impact forces can lead to significant economic loss for track owners through damage to rails and to the sleepers beneath. The wheel-rail impact forces occur because of imperfections on the wheels or rails such as wheel flats, irregular wheel profile, rail corrugation and differences in the height of rails connected at a welded joint. In this paper, a finite element model for the wheel flat study is developed by use of the FEA software package ANSYS. The effect of the wheel flat to impact force on sleepers is investigated. It has found that the wheel flat significantly increases impact forces and maximum Von Mises stress, and also delays the peak position of dynamic variation for impact forces on both rail and sleeper.

Failure analysis of laminated glass panels subjected to blast loads

This paper presents a rigorous and a reliable analytical procedure using finite element (FE) techniques to study the blast response of laminated glass (LG) panel and predict the failure of its components. The 1st principal stress (σ11) is used as the failure criterion for glass and the von mises stress (σv) is used for the interlayer and sealant joints. The results from the FE analysis for mid-span deflection, energy absorption and the stresses at critical locations of glass, interlayer and structural sealant are presented in the paper. These results compared well with those obtained from a free field blast test reported in the literature. The tensile strength (T) of the glass has a significant influence on the behaviour of the LG panel and should be treated carefully in the analysis. The glass panes absorb about 80% of the blast energy for the treated blast load and this should be minimised in the design.