published_or_final_version / abstract / Biochemistry / Master / Master of Philosophy

We discuss a systematic methodology that leads to the reconstruction of the material profile of either single, or assemblies of one-dimensional flexural components endowed with Timoshenko-theory assumptions. The probed structures are subjected to user-specified transient excitations: we use the complete waveforms, recorded directly in the time-domain at only a few measurement stations, to drive the profile reconstruction using a partial-differential-equation-constrained optimization approach. We discuss the solution of the ensuing state, adjoint, and control problems, and the alleviation of profile multiplicity by means of either Tikhonov or Total Variation regularization. We report on numerical experiments using synthetic data that show satisfactory reconstruction of a variety of profiles, including smoothly and sharply varying profiles, as well as profiles exhibiting localized discontinuities. The method is well suited for imaging structures for condition assessment purposes, and can handle either diffusive or localized damage without need for a reference undamaged state. / text

In the context of sustainable development, steelmakers and automotive manufacturers decided for some years now to join their efforts to promote the development and use of advanced high strength steels such as the present TRIP steels in order to reduce the fuel consumption and emission of greenhouse gas. These multiphase steels contain some retained austenite, a ductile phase that can transform into hard and brittle martensite during a mechanical solicitation. One the one hand, this transformation improves the mechanical properties during plasticity by bringing about an additional work-hardening. On the other hand, the appearence of a hard and brittle phase can give rise to premature cracking after necking. Knowing the good influence of martensitic transformation on the work-hardening, this Thesis starts with the characterisation of the relationship between transformation rates and testing conditions. It appears that, for each testing condition, there is an optimum austenite stability that leads to a maximum uniform strain. After necking under monotonic loading conditions, the damage mechanisms that takes place in these steels has been characterised. It can be concluded that the TRIP-aided steels that present low or moderate austenite stability behave exactly like Dual-Phase steels, in which martensite replaces retained austenite. However, a very stable retained austenite brings about a significant toughness improvement by providing an additional work-hardening contribution in the necking zone. The mechanical behaviour of these steels has also been characterised under cyclic loading conditions. The results indicate that, for particular loading conditions (i.e. low load levels), the martensitic transformation improves the fatigue properties.

<p align="justify">The conservation of structures of the historical heritage is an increasing concern nowadays for public authorities. The technical design phase of repair operations for these structures is of prime importance. Such operations usually require an estimation of the residual strength and of the potential structural failure modes of structures to optimize the choice of the repairing techniques.</p> <p align="justify">Although rules of thumb and codes are widely used, numerical simulations now start to emerge as valuable tools. Such alternative methods may be useful in this respect only if they are able to account realistically for the possibly complex failure modes of masonry in structural applications.</p> <p align="justify">The mechanical behaviour of masonry is characterized by the properties of its constituents (bricks and mortar joints) and their stacking mode. Structural failure mechanisms are strongly connected to the mesostructure of the material, with strong localization and damage-induced anisotropy.</p> <p align="justify">The currently available numerical tools for this material are mostly based on approaches incorporating only one scale of representation. Mesoscopic models are used in order to study structural details with an explicit representation of the constituents and of their behaviour. The range of applicability of these descriptions is however restricted by computational costs. At the other end of the spectrum, macroscopic descriptions used in structural computations rely on phenomenological constitutive laws representing the collective behaviour of the constituents. As a result, these macroscopic models are difficult to identify and sometimes lead to wrong failure mode predictions.</p> <p align="justify">The purpose of this study is to bridge the gap between mesoscopic and macroscopic representations and to propose a computational methodology for the analysis of plane masonry walls. To overcome the drawbacks of existing approaches, a multi-scale framework is used which allows to include mesoscopic behaviour features in macroscopic descriptions, without the need for an a priori postulated macroscopic constitutive law. First, a mesoscopic constitutive description is defined for the quasi-brittle constituents of the masonry material, the failure of which mainly occurs through stiffness degradation. The mesoscopic description is therefore based on a scalar damage model. Plane stress and generalized plane state assumptions are used at the mesoscopic scale, leading to two-dimensional macroscopic continuum descriptions. Based on periodic homogenization techniques and unit cell computations, it is shown that the identified mesoscopic constitutive setting allows to reproduce the characteristic shape of (anisotropic) failure envelopes observed experimentally. The failure modes corresponding to various macroscopic loading directions are also shown to be correctly captured. The in-plane failure mechanisms are correctly represented by a plane stress description, while the generalized plane state assumption, introducing simplified three-dimensional effects, is shown to be needed to represent out-of-plane failure under biaxial compressive loading. Macroscopic damage-induced anisotropy resulting from the constituents' stacking mode in the material, which is complex to represent properly using macroscopic phenomenological constitutive equations, is here obtained in a natural fashion. The identified mesoscopic description is introduced in a scale transition procedure to infer the macroscopic response of the material. The first-order computational homogenization technique is used for this purpose to extract this response from unit cells. Damage localization eventually appears as a natural outcome of the quasi-brittle nature of the constituents. The onset of macroscopic localization is treated as a material bifurcation phenomenon and is detected from an eigenvalue analysis of the homogenized acoustic tensor obtained from the scale transition procedure together with a limit point criterion. The macroscopic localization orientations obtained with this type of detection are shown to be strongly related to the underlying mesostructural failure modes in the unit cells.</p> <p align="justify">A well-posed macroscopic description is preserved by embedding localization bands at the macroscopic localization onset, with a width directly deduced from the initial periodicity of the mesostructure of the material. This allows to take into account the finite size of the fracturing zone in the macroscopic description. As a result of mesoscopic damage localization in narrow zones of the order of a mortar joint, the material response computationally deduced from unit cells may exhibit a snap-back behaviour. This precludes the use of such a response in the standard strain-driven multi-scale scheme.</p> <p align="justify">Adaptations of the multi-scale framework required to treat the mesostructural response snap-back are proposed. This multi-scale framework is finally applied for a typical confined shear wall problem, which allows to verify its ability to represent complex structural failure modes.</p>

No description available.

As a result of medical advancement and cultural patterns of Western society, traumatic head injury is increasingly a problem for the injured, their families, medical and social services professionals, and the community at large. Head trauma is remarkable because of the complex nature of the residual disabilities which include long lasting cognitive and emotional problems, social isolation, and family disruption. The purpose of this study was to re-examine the phenomenon of recovery after mild to moderate head injury using an ethnographic research approach. The data were based on the experiences of 21 disabled and their families in the community setting. The disabled represented a range of stages of recovery and severity of disability. The data was collected using three field work strategies: extensive semi-structured interviews, participant observation, and non-academic document review. After collection the data was subjected to thematic and content analysis, that resulted in the selection of themes that characterized the experiences for the head injured and their families. The themes for the head injured informants were: dead days, loneliness, and forgetting. The family members' experiences were represented in the themes: responsibility, vulnerability, tough love, gender differences, and reactions to the experience. Next the data were interpreted using five theoretical concepts from cultural anthropology: liminality, personhood, social labelling, sick role and double bind. In addition, the reflexive influence of the investigator on the research process was addressed. The trustworthiness of the ethnography was assessed in terms of credibility, transferability, dependability and confirmability. Several variables were found to be important to the long term outcome of head injury. These variables were: family directed therapy, double bind communication patterns, and lifelong recovery. Two other factors were found to be critical for the recovery of the head injured. These were economic disincentives to the return to employment and the importance of the social and family environment. In the final section the research and policy implications of the study were discussed in relation to management and service provisions.

This study investigated the relationship between the Wechsler Adult Intelligence Scale-Revised (WAIS-R) and the Stanford-Binet Intelligence Scale: Fourth Edition (SBIV) in a brain-damaged adult sample. The sample in this study was composed of 30 adult patients at two residential treatment programs who completed comprehensive psychological evaluations between August, 1986 and November, 1987. Each patient was administered both the WAIS-R and the SBIV as part of these evaluations. Data gathered in this study was submitted to Pearson product moment correlational statistical procedures. Significant correlations were found in the following pairs of summary scores: the SBIV Test Composite Standard Age Score (SAS) and the WAIS-R Full Scale IQ; the SBIV Abstract/Visual Reasoning Area SAS and the WAIS-R Performance IQ; the SBIV Quantitative Reasoning Area SAS and the WAIS-R Verbal Scale IQ; the SBIV Verbal Reasoning Area SAS and the WAIS-R Verbal Scale IQ; the SBIV Short-Term Memory Area SAS and the WAIS-R Verbal Scale IQ; and the SBIV Short-Term Memory Area SAS and the WAIS-R Full Scale IQ. Significant correlations were also found in the following pairs of individual subtest results: the SBIV and WAIS-R Vocabulary subtests; the SBIV Memory for Digits subtest and the WAIS-R Digit Span subtest; the SBIV Pattern Analysis subtest and the WAIS-R Block Design subtest; and the SBIV Paper Folding and Cutting subtest and the WAIS-R Picture Arrangement subtest. Directions for future research were also suggested upon review of the subtest correlation matrix and the descriptive statistics of data generated.

Barrett's esophagus (BE) is a premalignant disease associated with esophageal adenocarcinoma (EAC). This condition is highly associated with gastroesophageal reflux disease (GERD) which is characterized as chronic exposure of the esophagus to acid and bile acids. An understanding of the cytotoxic and tumorigenic capacity of bile acids and acid during a reflux episode will lead to the identification of markers for therapeutic intervention. The major goal of the following studies was to determine the mechanisms responsible for bile acid-induced alteration in intracellular pH (pHi) the effect on DNA damage, apoptosis and the adaptive resistance to reflux episodes in cells derived from normal esophagus (HET1A) or BE (CP-A) and EAC (JH-EsoAd1). In addition, I explored the therapeutic potential of UDCA oral therapy in BE cells.Here we show a novel mechanism of bile acid-induced, nitric oxide-mediated inhibition of the sodium-hydrogen exchanger (NHE) is a pathway bile acids utilize to induce acid-mediated DNA damage. This same mechanism can elicit apoptosis-resistance which we demonstrate by the complete inhibition of NHE with pharmacological inhibitor of NHE, EIPA. In addition, chronic exposure of bile acids and acid, in-vitro, confers resistance to cytotoxicity and makes cells derived from the squamous epithelium of the esophagus resemble BE and EAC. Finally, modifying the bile acid composition with glycol-Ursodeoxycholic acid (GUDCA) prevents many of the malignant effects of bile acids and acid and suggests a possible therapeutic strategy for those that suffer from GERD. The conclusion from this study suggest that bile acid reflux should be controlled in patients who suffer from GERD

Uranium has been mined for many years and used for fuel for nuclear reactors and materials for atomic weapons, ammunition, and armor. While the radioactivity associated with uranium mining has been linked to the development of lung and kidney cancers, and leukemia, little is known about the direct chemical genotoxicity of uranium. The overall hypothesis of the current research is that uranium can produce DNA damage by chemical genotoxicity mechanisms. Three specific aims were tested. In Aim 1, specific DNA lesions caused by direct interaction of uranium and DNA were investigated. Chinese Hamster Ovary cells (CHO) with mutations in various DNA repair pathways were exposed to 0 – 300 μM of soluble depleted uranium (DU) as uranyl acetate (UA) for 0 – 48 hr. Results indicate that UA readily enters CHO cells, with the highest concentration localizing in the nucleus. Clonogenics assay shows that UA is cytotoxic in each cell line with the greatest cytotoxicity in the base excision repair deficient EM9 cells and the nuclear excision repair deficient UV5 cells compared to the non-homologous end joining deficient V3.3 cells and the parental AA8 cells after 48 hr. This indicates that UA is forming DNA adducts that may be producing single strand breaks through hydrolysis rather than double strand breaks in CHO cells. Fast Micromethod® results indicate an increased amount of single strand breaks in the EM9 cells after 48 hr UA exposure compared to the V3.3 and AA8 cells. In Aim 2, the role of oxidative stress in producing DNA lesions was determined. Cellular oxidative stress has been implicated in the genotoxicity of many heavy metals as a mechanism of induced DNA damage. To investigate this possible mechanism, human bronchial epithelial cells (16HBE14o⁻) were exposed to 30 ppb (0.13 μM U) UA for 2 – 24 hr. UA did not significantly induce oxidative stress compared to untreated cells at 3 – 4 hr time points. These results suggest that cellular oxidative stress is not a major pathway of DU genotoxicity at low concentrations. In Aim 3, DNA damage response to uranium-induced DNA damage was investigated. It has been widely reported that metals can be genotoxic by inhibiting DNA repair. Cultured cells were co-exposed to 0.13 μM UA in the presence of 0 – 25 μM of etoposide for 0 – 48 hr. Results indicate that UA inhibited double strand break repair. Coexposures of etoposide and UA synergistically induced cytotoxicity compared to individual treatments and untreated cells. Co-exposed UA and etoposide treated 16HBE14o⁻ cells exhibited a decrease in phosphorylation of DNA repair proteins compared to etoposide treatments. Untreated and UA-treated 16HBE14o⁻ cells did not induce phosphorylation of DNA repair proteins. These results suggest that DU inhibits double strand break DNA repair at low concentrations in the presence of a known DNA double-strand damaging agent, etoposide. The inhibition of DNA repair by DU at environmentally relevant concentrations suggests a novel means by which uranium may exert its genotoxic effects. Results found at low dose exposures are not consistent with alterations seen with radioactivity, suggesting that the effects of uranium at low doses are due to its chemical genotoxic effects. Understanding how uranium reacts with DNA is important to better understand how this suspected carcinogen induces cancer and to help to elucidate mechanisms that produce cancers in people exposed to uranium.

Large optical systems fabrication is a demanding task due to the tight requirements and big scales. To make mirrors up to 8.4m in diameter necessitates technological development in materials, tooling, and metrology. These advancements are designed to not only produce optics on a near-unheard of scale, but to improve fabrication methods with each piece.For an optical surface to be properly polished, the amount of material removed during polishing must be greater than the volume of damage left behind by the grinding process. Mixed-mode grinding, which combines bound abrasives with a compliant binder material, is a valuable tool at this stage as it creates less damage while maintaining a fast and uniform cutting rate than traditional loose abrasive grinding.These materials are challenging for large optical surfaces due to the honeycomb structures used to lightweight the mirrors. Development is done to adapt the abrasive to handle the very low pressures and speeds required to avoid imprinting structure on the optical surface.We take a comprehensive approach in measuring mixed-mode behavior using 3M Trizact™. Prior works on bound abrasives have focused on specific properties: removal rates, subsurface damage, etc. None have yet to look at the entire scope of the material and its benefits. These properties will be analyzed along with different behaviors regarding surface scattering, Twyman effect bending moments, glazing, manufacturing expenses, and failure mechanisms. This comprehensive understanding of the abrasive allows manufacturers to create better grinding schedules and reduce overall expenses in fabrication.Trizact shows up to a three times faster removal rate while producing 30\% less subsurface damage than loose abrasives of similar size. Additionally, the surface has scatters less light which can be adapted through changes in processing to create a specular reflection for optical surface metrology.Based on our findings, this type of abrasive integrates into current optical fabrication processes as a pre-polishing material. Here, the transition to these abrasives becomes cost effective by rapidly eliminating damage created during the generating of the surface and reducing the amount of polishing required.