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.

The exploitation of sandwich structures as a means toachieve high specific strength and stiffness is relatively new.Therefore, the knowledge of its damage tolerance is limitedcompared to other structural concepts such as truss bars andmonocoque plate solutions. Several aspects of the damage tolerance of sandwichstructures are investigated. The influence of impact velocityonresidual strength is investigated. Sandwich panels withfaces of glass fiber reinforced vinylester are impacted bothwith very high velocity and quasi static. The residual strengthafter impact is found to be similar for both cases of impactvelocity. Curved sandwich beams subjected to opening bending momentare studied. Faceñcore debonds of varying size areintroduced between the compressively loaded face sheet and thecore. Finite element analysis in combination with a pointstress criterion is utilized to predict the residual strengthof the beams. It is shown that it is possible to predict thefailure load of the beams with face-core debond. Using fractography the governing mode of failure ofcompressively NCF-carbon is characterized. Sandwich panelssubjected to compression after impact are shown to fail byplastic micro buckling. The residual compressive strength after impact of sandwichpanels is investigated. Sandwich panels with face sheets ofnon-crimp fabric (NCF) carbon are subjected to different typesof impact damages. Predictions of residual strength are madeusing the Budiansky, Soutis, Fleck (BSF) model. The residualstrength is tested, and the results are compared topredictions. Predictions and tests correlate well, and indicatethat the residual strength is dependent on damage size and notthe size of the damaged panel. A study of the properties of a selection of fiberreinforcements commonly used in sandwich panels is conducted.The reinforcements are combined with two types of core materialand three types of matrix. Also the influence of laminatethickness is tested. Each combination materials is tested inuni-axial compression, compressive strength after impact andenergy absorption during quasi static indentation. Thespecimens which are tested for residual strength are eithersubjected to quasi-static or dynamic impact of comparableenergy level. Prediction of the residual strength is made andcorrelates reasonably whith the test results. The tests showthat if weight is taken into account the preferred choice offiber reinforcement is carbon.

<p>QC 20120928</p>

The main aim of this thesis was to study the role of the indirect actions of γ-rays and α-particles on the complexity of primary DNA damages and the repair fidelity of major DNA repair pathways: non-homologous end joining (NHEJ), homologous recombination repair (HRR) and base excision repair (BER). The complexity of radiation-induced damages increases and the proximity between damages decreases with increasing LET due to formation of ionization clusters along the particle track. The complexity of damages formed can be modified by the free radical scavenger dimethyl sulfoxide (DMSO). In addition, the effects of low doses of low dose rate γ-radiation on cellular response in terms of differentiation were investigated. Paper I investigates the role of the indirect effect of radiation on repair fidelity of HRR, NHEJ and BER when damages of different complexity were induced by radiation or by potassium bromate. We found that potassium bromate induces complex DNA damages through processing of base modifications and that the indirect effect of radiation has a high impact on the NHEJ pathway. Results in paper II confirmed our conclusions in paper I that the indirect effect from both γ-rays and α-particles has an impact on all three repair pathways studied and NHEJ benefits the most when the indirect effect of radiation is removed. In paper III we investigated the effects of low dose/dose rate γ-radiation on the developmental process of neural cells by using cell models for neurons and astrocytes. Our results suggest that low dose/dose rate γ-radiation attenuates differentiation and down-regulates proteins involved in the differentiation process of neural cells by an epigenetic rather than cytotoxic mechanism. / <p>At the time of doctoral defense, the following paper was unpublished and had a status as follows: Paper 2: Manuscript.</p>

This thesis has two parts. In the first part, we use the results of new fatigue experiments conducted with variable load levels as well as variable stress ratios to critically assess three (two old and one relatively new) cumulative fatigue damage models. These models are deterministic. Such models are usually tested using multiple blocks of periodic loading with differing amplitudes. However, available data pertains to zero-mean loading, and does not investigate the role of variable stress ratio (Smin/Smax). Here, we present experimental results for variable stress ratios. Two specimen geometries and two materials (Al 2014and Al 2024)are tested. Manson’s double linear damage rule (DLDR)gives the highest accuracy in predicting the experimental outcome, even in the presence of variable stress ratios, whereas predictions of the newer model (“A constructive empirical theory for metal fatigue under block cyclic loading,” Proceedings of the Royal Society A, 464 (2008), 1161-1179) are slightly inferior. The widely used Miner’s rule is least accurate in terms of prediction. The merits and drawbacks of these models, in light of the experimental results, are as follows. The DLDR, though accurate, has minor scientific inconsistencies and no clear generalization. The constructive model has possible generalizability and more appealing scientific consistency, but presently has poorer accuracy. Miner’s rule, least accurate, lies within the constructive approach for special parameter values. The DLDR can guide the new (constructive)approach through new parameter fitting criteria. In the second part of this thesis, we consider the scatter in fatigue life and use the Weibull distribution to describe ‘S-N-P’ curves. We first assume homoscedasticity (load-independent or constant variance) and present a way to draw a p-percentile line on a log-log load-life plot. Then heteroscedasticity (load-dependent variance) in fatigue life is incorporated and a simple statistical model is proposed, to obtain a straight line percentile plot at a pre-specified probability of survival ps. The proposed method is illustrated for Al 2014-T6 and Al 2024-T4 data sets (extracted manually) from MMPDS-01 (a data handbook).

In this dissertation, experimental investigations and theoretical studies on the stochastic matrix cracking evolution under static and fatigue loading in composite laminates with defects are presented. The presented work demonstrates a methodology that accounts for the statistically distributed defects in damage mechanics models for the assessment of the integrity of composites and for the structural design of composites. The experimental study deals with the mechanisms of the formation of a single crack on a micro-scale and the stochastic process for the multiplication of cracks on a macro-scale. The defects introduced by the manufacturing processes are found to have significant effect on the matrix cracking evolution. Influenced by the distributed defects, the initiation and multiplication of cracks evolve in a stochastic way. The experimental study on the in-plane shear stress finds the detrimental effect of the shear stress on the fatigue performance of composite laminates. Combined with the transverse tensile stress, the in-plane shear stress induces multiple inclined microcracks in the matrix, which enhance the initiation and propagation of the major matrix cracks. Based on the experimental investigations, a statistical model for the stochastic matrix cracking evolution on the macro-scale is developed. Simulations based on the statistical model yield accurate predictions for both static and fatigue loading compared to the experimental data. The Weibull distribution of the static strength is estimated by the statistical model by comparing against the experimental crack density data. The estimated Weibull distribution of the static strength provides an efficient approach to characterize the manufacturing quality of composite laminates. Compared to deterministic approaches, the Weibull distribution of the static strength provides comprehensive information of the strength property of composite laminates.

Gene regulatory networks are dynamic and continuously remodelled in response to internal and external stimuli. To understand how these networks alter cellular phenotype in response towards specific challenges, my first project sought to develop a methodology to explore how the strength of genetic interactions changes according to environmental context. Defined as sensitivity-based epistasis, the results obtained using this methodology were compared to those generated under the conventional fitness-based approach. By integrating this information with gene expression profiles and physical interaction datasets, we demonstrate that sensitivity-based epistasis specifically highlights genetic interactions with a dynamic component. Having investigated how an external stimulus regulates network dynamics, we next sought to understand of how genome positioning impacts transcription kinetics. This feat was accomplished by cloning two gene-reporter constructs, representing contrasting promoter architectures, across 128 loci along chromosome III in S.Cerevisiae. By comparing expression and noise measurements for promoters with “covered” and “open” chromatin structures against a stochastic model for eukaryotic gene expression, we demonstrate that while promoter structure regulates burst frequency (the rate of promoter activation), positional effects in turn appear to primarily modulate burst size (the number of mRNA produced per gene activation event). By integrating these datasets with information describing global chromatin structure, we suggest that the acetylation state of chromatin regulates burst size across the genome. Interestingly, this hypothesis is further supported by nicotinamide-mediated inhibition of Sir2 which would appear to modulate burst size globally across the genome.

The reliability of modern gas turbine engines is largely due to careful damage tolerant design a method of structural design based on the assumption that flaws (cracks) exist in any structure and will continue to grow with usage. With proper monitoring, largely in the form of periodic inspections at conservative intervals reliability and safety is maintained. These methods while reliable can lead to the early retirement of some components and unforeseen failure if design assumptions fail to reflect reality. With improvements to sensor and computing technology there is a growing interest in a system that could continuously monitor the health of structural aircraft as well as forecast future damage accumulation in real-time. Through the use of two-dimensional and three-dimensional numerical modeling the initial goals and findings for this continued work include: (a) establishing measurable parameters directly linked to the health of the blade and (b) the feasibility of detecting accumulated damage to the structural material and thermal barrier coating as well as the onset of damage causing structural failure.

The 2004 Indian Ocean and 2011 Tohoku tsunami events have shown the destructive power of tsunami inundation to the constructed environment in addition to the tragic loss of life. A comparable event is expected for the Cascadia Subduction Zone (CSZ) which will impact the west coast of North America. Research efforts have focused on understanding and predicting the hazard to mitigate potential impacts. This thesis presents two manuscripts which pertain to estimating infrastructure damage and determining design loads of tsunami inundation. The first manuscript estimates damage to buildings and economic loss for Seaside, Oregon, for CSZ events ranging from 3 to 25 m of slip along the entire fault. The analysis provides a community scale estimate of the hazard with calculations performed at the parcel level. Hydrodynamic results are obtained from the numerical model MOST and damage estimates are based on fragility curves from the recent literature. Seaside is located on low lying coastal land which makes it particularly sensitive to the magnitude of the events. For the range of events modeled, the percentage of building within the inundation zone ranges from 9 to 88%, with average economic losses ranging from $2 million to $1.2 billion. The second manuscript introduces a new tsunami inundation model based on the concept of an energy grade line to estimate the hydrodynamic quantities of maximum flow depth, velocity, and momentum flux between the shoreline and extent of inundation along a 1D transect. Using the numerical model FUNWAVE empirical relations were derived to tune the model. For simple bi-linear beaches the average error for the tuned model in flow depth, velocity, and momentum flux were 10, 23, and 10%, respectively; and for complex bathymetry at Rockaway Beach, Oregon, without recalibration, the errors were 14, 44, and 14% for flow depth, velocity, and momentum flux, respectively. / Graduation date: 2013

The application of the synthetic mineralocorticoid, deoxycorticosterone acetate (DOCA)-salt, to unilaterally nephrectomised rats induces severe hypertension due to volume-overload, and mimics human primary aldosteronism. Importantly, DOCA-salt hypertension is characterized by severe cardiac and renal lesions triggered by nuclear factor kappa B (NF-kappaB), activating protein (AP-1), and transforming growth factor beta1 (TGF-beta1) leading to end-stage organ damage. Although DOCA-salt hypertension is a low renin model, local production of angiotensin-II and aldosterone in cardiac and renal tissues stimulate TGF-beta1, fibronectin and collagen-1 causing fibrosis and hypertrophy. Since TGF-beta1 gene promoter contains binding sites for NF-kappaB and AP-1, cross-talk between TGF-beta1, NF-kappaBnand AP-1 can be envisaged. Accordingly, the activation of TGF-beta1, fibronectin, collagen, NF-kappaB and AP-1 may constitute a potent destructive force in hypertension.<p> Emerging evidence indicates that upregulation of the heme oxygenase (HO) system is cytoprotective with antioxidant, antihypertensive and antihypertrophic effects. Interestingly, the promoter region of HO-1 gene harbors consensus-binding sites for NF-kappaB and AP-1; therefore, the HO system may regulate these transcription factors to counteract tissue insults. However, the multifaceted interactions between the HO system, NF-kappaB, AP-1, TGF-beta1, fibronectin and collagen in mineralocorticoid-induced end-stage-organ damage have not been fully characterized. Similarly, the effect of the HO system on tissue angiotensin-II and aldosterone levels in mineralocorticoid-induced hypertension remains unclear. Therefore, the present study was designed to investigate the antihypertrophic effect of the HO system in cardiac and renal tissue of DOCA-salt hypertensive rats. In this study, the HO inducer, hemin, lowered blood pressure and attenuated cardiac/renal hypertrophy, whereas the HO inhibitor, chromium mesoporphyrin (CrMP), nullified the effects of hemin and exacerbated cardiac/renal injury the DOCA-salt hypertensive rats. The protective effect of hemin was associated with increased HO-1, HO activity, cyclic guanosine monophosphate (cGMP), superoxide dismutase activity, ferritin and the total antioxidant capacity in the cardiac and renal tissue. In contrast, angiotensin-II, aldosterone, 8-isoprostane, NF-kappaB and AP-1 were significantly downregulated. Furthermore, hemin therapy attenuated TGF-beta1 and extracellular matrix (ECM) proteins such as fibronectin and collagen, with corresponding reduction of cardiac histopathological lesions, including longitudinal/cross-sectional muscle fiber thickness, scarring, muscular hypertrophy, coronary arteriolar thickening and collagen deposition. Similarly, hemin attenuated structural lesions in the kidney such as glomerular hypertrophy, glomerular sclerosis, mononuclear cell infiltration, tubular cast formation, tubular dilation and renal arteriolar thickening with concomitant improvement of kidney function as evidenced by reduction of plasma creatinine, proteinuria, but enhanced creatinine clearance.<p> Collectively, these results suggest that the HO system suppressed hypertension, cardiac and renal fibrosis, and hypertrophy in the DOCA-salt hypertensive rat by downregulating transcription factors such as NF-kappaB and AP-1, reducing ECM proteins such as fibronectin and collagen, decreasing local tissue production of angiotensin-II and aldosterone, and improved renal functional capacity.