2,5-diaminoimidazolone (Iz) is an important product of a 4-electron oxidation of guanine. The present research focuses on the mechanisms of formation of Iz via pathways initiated by guanine oxidation by one-electron oxidants (OEOs) generated by X-ray radiolysis in aqueous solutions. The kinetics of formation and yields of Iz in reactions of native highly polymerized DNA with different OEOs have been compared using an HPLC-based quantitative analysis of low-molecular products generated from the reaction of DNA-bound Iz with primary amines. Mechanisms of Iz formation in DNA have been investigated including oxygen and superoxide dependence as well as the hypothesis that 8-oxo-G, another product of guanine oxidation, is not a major precursor to Iz. Results indicate Iz is produced in significant quantities in DNA from guanine oxidation and the efficiency of its formation correlates with the reduction potential and selectivity of a given OEO.

In reconstruction of on-roadway vehicle accidents, roadway surface gouges and the forces and energy attributed to the related vehicle components become important keys to resolving an accurate accident reconstruction. These roadway gouge forces vary depending upon such factors as surface temperature and the velocity and geometry of the gouging mechanism. Accounting for the forces applied to vehicle components and the energy dissipated from such forces can be helpful in accident reconstruction where supporting data exists. This research documents the force necessary to create a given roadway gouge geometry. Controlled pavement gouging tests were performed using roadway surface temperature and gouging velocity as main factors. The results of this testing and analysis are useful in quantifying gouge forces and energies for use in accident reconstruction. The findings show that the temperature of the roadway surface that is being damaged significantly affects the amount of force required to cause the damage. A summary of experiments and techniques as applied to accident reconstruction are presented.

An explosion is characterized as a sudden release of large energy over a very short duration. As the blast wave travels parallel to a surface, it creates a side-on pressure and when it hits a surface perpendicularly or at an angle, it creates a reflected pressure. Side-on pressure and reflected pressure are much higher than service loads for the structure. Thus, when a blast happens near a building that is not designed to withstand blast loads, it can cause catastrophic damage. The objective of this study is to present a formulation for the design optimization of framed steel structures subjected to blast loads. Also, a formulation is presented for the design optimization of structures that can withstand some possible damage due to blast loads. To this end, an optimization procedure that includes definitions of design variables, cost function, constraints, and structural analyses is discussed. The design variables for beams and columns are the discrete values of the W-shapes selected from American Institute of Steel Construction (AISC) tables. The optimization problem is to minimize the total structural weight subjected to AISC strength requirements and blast design displacement constraints. Linear static, linear dynamic, and nonlinear dynamic analyses are incorporated in the optimization process and optimum designs are compared. Due to design variables and some constraints discontinuity, gradient-based optimization algorithms cannot be used to solve the optimization problem. Therefore, metaheuristic algorithms are used that require only simulation results to solve problems with discrete variables and non-differentiable functions. Since the number of simulations and robustness to obtain good designs are important for the class of problems discussed in this research, a new hybrid optimization algorithm based on Harmony Search (HS) and Colliding Bodies Optimization (CBO) is developed and examined. The algorithm is named Hybrid Harmony Search - Colliding Bodies Optimization (HHC). Also, a novel design domain reduction technique is incorporated in HHC. Some benchmark discrete variable structural design problems are used to evaluate HHC. In comparison with some popular metaheuristic optimization algorithms, HHC is shown to be robust, effective, and needs fewer structural analyses to obtain the best designs. Depending on the size of the structure to be designed, optimization of structures that require linear or nonlinear dynamic analyses using metaheuristic algorithms can be computationally expensive because these types of algorithms need large number of simulations to reach good designs. Equivalent Static Loads (ESL) approach, which has been used for optimization of structural systems subjected to dynamic loads using gradient-based algorithms, is examined for optimization of structures that have discrete design variables using metaheuristic algorithms. The proposed approach is named global optimization with equivalent static loads (GOESL). Solution of four numerical examples shows that GOESL can drastically reduce the number of dynamic analyses needed to reach the best design compared to an algorithm without the ESL approach. However, the ESL step alone cannot converge to the best design for the current formulation, even with many ESL cycles. Therefore, after a few ESL cycles, the procedure may switch to the original algorithm without the ESL cycles to improve designs further. HHC and GOESL are used to solve three-dimensional framed steel structures subjected to blast loads with linear and nonlinear dynamic analyses as separate solution cases. The source of the blast loads is a car carrying 250 lbs of Trinitrotoluene (TNT) with 50 ft standoff distance from the front face of a 4-bay x 4-bay x 3-story building. Optimum designs of the structure to withstand blast loads show that penalty on the optimum structural weight is substantial when linear dynamic analysis is used. With nonlinear dynamic analysis, the penalty on the structural weight is substantially reduced. When the stiffness of the walls is included in the analysis model, there is very little penalty on the optimum structural weight with linear or nonlinear dynamic analysis models. The best designs obtained with the linear and nonlinear dynamic analysis models are checked for some possible damages due to a blast. Two types of damage conditions are defined: (i) complete removal of some key members from the analysis model, and (ii) reduction of stiffness of some members. It is shown that the best designs using linear or nonlinear dynamic analyses can withstand all damage conditions. Thus, resilience of the designs to withstand blast loads is observed.

Emotion regulation is an ability that humans engage in throughout their lives. Disruption in this ability due to brain injury can have devastating consequences on the ability to function adaptively in complex environments. It has been observed that damage involving certain areas of the prefrontal cortex (PFC), including the ventromedial PFC (VMPFC), can result in long-lasting impairments in real-world emotional and behavioral functioning. However, the specific areas of the PFC that are critical for the ability to regulate emotion have not been identified. The primary aims of this project were to identify areas of the PFC that are important for the regulation of emotion, and to determine the degree to which impairments in emotion regulation may contribute to real-world dysfunction following damage to the PFC. To address these aims, emotional regulation and real-world functioning were examined in a sample of patients with focal PFC lesions. Damage involving the VMPFC appeared to have limited impact on the ability to voluntarily regulate emotion. It was also observed that damage to PFC regions outside the VMPFC was associated with reduced ability to overcome distraction by salient emotional stimuli, compared to VMPFC damage. However, analyses of lesion volume showed that more extensive damage involving the VMPFC was associated with greater emotional distraction, suggesting one form of emotional dysregulation that may result from damage to the VMPFC. In addition, it was found that brain damage in general was associated with impairments in real-world functioning, though PFC damage was not associated with more striking impairments compared to damage outside the PFC. These findings suggest that damage involving certain PFC regions can disrupt the ability to effectively regulate emotion. The results from this project also suggest that laboratory measures of emotion regulation may help in predicting real-world dysfunction following brain damage.

Micromechanical simulations are conducted to quantify the influence of microstructure attributes to the formation of small fatigue cracks. Three wrought aluminum alloys (7075-T651, 2024-T3, virtual material) with fractured particle are studied to quantify the influence of material’s yield strength and ultimate strength to material’s fatigue resistance. Laser Engineered Net Shaping (LENS) material with pores of various spatial distribution and particles are simulated for the microplasticity and its effects on fatigue incubation. A cohesive zone model is used to study the interface cohesive behavior’s influence to the cyclic driving mechanisms. Different simulations based on different interfacial crack geometries and particle shapes are studied. A cohesive law with unloading-reloading cyclic behavior is introduced. A damage factor D is proposed to study the possibility of interfacial crack propagation. With this factor, plastic wake zone behind the debonding is studied.

La conception et la réalisation des tests de qualification des engins propulsés nécessitent une connaissance du comportement mécanique des matériaux utilisés pour leur fabrication. Dans ce cadre, une large gamme de vitesses de sollicitation est à considérer, intégrant de nombreuses situations de service des propergols solides. La connaissance de leur comportement doit permettre de prédire les risques associés à une sollicitation imprévue (conditions de transport difficiles, chute). La méthodologie usuelle consiste en la caractérisation des matériaux par un ensemble d’essais de traction uniaxiale, d’essais de DMA et d’essais de traction sous pression pour identifier les paramètres du modèle numérique (HRVM). Cependant, il a été indiqué que la méthodologie usuelle ne permettait pas la réalisation de simulations numériques satisfaisantes lorsque la vitesse de déformation est supérieure à 50 s−1. Ce travail de thèse propose des nouvelles techniques de caractérisation expérimentale permettant de compléter les résultats existants pour une gamme de vitesse de l’ordre de 100 s−1. Des essais originaux assurant des modes de sollicitations dynamiques et homogènes ont été mis au point et validés. Par exemple, un montage expérimental de traction uni-axiale rapide a été conçu pour la caractérisation d’un élastomère composite à matrice p − BHT hautement chargé de particules rigides (une distribution de CaCO3 et une autre d’aluminium). Parmi les autres essais développés, un essai de cisaillement hétérogène d’impact sur tranche a été adapté, cet essai permet d’apprécier l’état d’endommagement dans le matériau pendant et suite à l’impact. Les paramètres de comportement quantifiés dans la gamme de vitesse de déformation prospectée ont été intégrés à la bibliothèque des paramètres existante. Les premières simulations numériques intégrant ces nouveaux paramètres ont permis d’étendre l’utilisation du modèle de comportement utilisé par Ariane Group. / The design and qualification tests of rocket motors require knowledge of the mechanical behavior of the materialsused to manufacture them. In this aim, a large range of strain rates have to be considered, this range integratemany solid propellant service situations. Knowledge of their behaviour should make it possible to predict the risksassociated with unexpected stress on propelled vehicles (difficult transport conditions, falls). The usual methodologyuses both numerical and experimental approaches. This methology is based on several uniaxial tesile tests, DMA andtensile tests under pressure to identify the parameters of the constitutive law (HRVM). However, it was indicatedthat the usual method did not allow satisfactory numerical predictions to be performed when the strain rate isgreater than 50 s−1. This PhD work proposes new experimental characterization techniques to complement existingresults for a range of strain rates of about 100 s−1. Original tests ensuring dynamic and homogeneous loadingshave been developed. A dynamic tensile test has been designed to characterize composites elastomers highly filled(CaCO3 and aluminum). A heterogeneous dynamic shear test of edge-on impact has been also adapted, this testmakes it possible to assess the state of damage in the material during and after the impact. The material parametersquantified with new mechanical tests have been integrated into the existing parameter library. The firsts numericalsimulations using these new parameters have made it possible to extend the practice of numerical model used byAriane Group.

DNA double strand break (DSB) repair is critical to maintain genomic integrity and cell viability. DSBs can occur during the course of cell cycle during replication or transcription, or by exogenous agents such as chemicals or ionizing radiation. For my thesis, I studied homologous recombination (HR), which has two sub-pathways: Homology Directed Repair (HDR) and Single Strand Annealing (SSA). HDR involves strand invasion of a homologous template to prime DNA synthesis; SSA involves annealing of homologous segments flanking a DSB. Background data showed that depletion of XAB2 protein by RNA interference reduced both HDR and SSA events. XAB2 protein contains 15 tetratricopeptide repeat (TPR) motifs, which likely enable protein-protein interactions. While XAB2 is speculated to have a role in transcription coupled repair and pre-mRNA splicing, its role in HR pathway is uncertain. The overall hypothesis for my thesis is that XAB2 mediates a specific step of HR (5’-3’ end resection), and the TPR motifs present in XAB2 enable the protein to function in a complex during HR. By using an end resection assay and cell biology analysis, I found that XAB2 is essential for 5’ – 3’ end resection, an intermediate step common to both HDR and SSA pathways. With a functional complementation assay I developed, I have shown that specific TPR regions are critical for XAB2 functions in HR. Overall, my research demonstrates that XAB2 protein has a key role in the 5’-3’ end resection step of HR, and its function in HR requires specific sets of its TPR regions.

The purpose of this study was to examine and compare inferential abilities on a reading comprehension task in two groups of adults who had suffered cerebrovascular accidents (CVA). Sixteen subjects with a CVA to the right hemisphere of the brain were compared to an equal number of left hemisphere damaged subjects. Subjects were selected after they had demonstrated an adequate level of functioning on the Short Porch Index of Communicative Ability (SPICA), a test which measures communicative efficiency, to perform the tasks required in this study. All subjects were administered the revised version of the Nelson Reading Skills Test (NRST). On the NRST, test questions can be grouped into three categories representing literal, translational and high levels of inference. Subjects were presented five reading paragraphs. They were asked to answer thirty-three questions pertaining to the reading material by pointing to the correct answer out of four choices. Subjects were allowed to refer back to the paragraphs when trying to answer the questions. Results revealed total NRST performance to be significantly better for RBD subjects. RBD subjects also performed significantly better than LBD subjects on translational inference items. The research data did not reflect the expected error pattern with most errors on questions requiring high inferential abilities followed by translational items and fewest errors on literal inferences for either group of subjects.

Break Induced Replication (BIR), a mechanism by which cells heal one-ended double-strand breaks, involves the invasion of a broken strand of DNA into a homologous template, and the copying of tens to hundreds of kilobases from the site of invasion to the telomere using a migrating D-loop. Here we show that if BIR encounters an interstitial telomere sequence (ITS) placed in its path, BIR terminates at the ITS 12% of the time, with the formation of a new telomere at this location. We find that the ITS can be converted to a functional telomere by either direct addition of telomeric repeats by telomerase, or by homology-directed repair using natural telomeres. This termination and creation of a new telomere is promoted by Mph1 helicase, which is known to disassemble D-loops. We also show that other sequences that have the potential to form new telomeres, but lack the unique features of a perfect telomere sequence, do not terminate BIR at a significant frequency in wild-type cells. However, these sequences can cause chromosome truncations if BIR is made less processive by loss of Pol32 or Pif1. These findings together indicate that features of the ITS itself, such as secondary structures and telomeric protein binding, pose a challenge to BIR and increase the vulnerability of the D-loop to dissociation by Mph1, promoting telomere formation at the site.

Vibration-based damage detection methods are used in structural applications to identify the global dynamic response of the system. The purpose of the work presented is to exhibit a vibration-based damage detection algorithm that calculates a damage indicator, based on limited frequency bands of the transmissibility function that have high coherence, as a metric for changes in the dynamic integrity of the structure. The methodology was tested using numerical simulation, laboratory experimentation, and field testing with success in detecting, comparatively locating, and relatively quantifying different damages while also parametrically investigating variables which have been identified as issues within similar existing methods. Throughout both the numerical and laboratory analyses, the results were used to successfully detect damage as a result of crack growth or formation of new cracks. Field results using stochastic operational traffic loading have indicated the capability of the proposed methodology in evaluating the changes in the health condition of a section of the bridge and in consistently detecting cracks of various sizes (30 to 60 mm) on a sacrificial specimen integrated with the bridge abutment and a floor beam. Fluctuations in environmental and loading conditions have been known to create some uncertainties in most damage detection processes; however, this work demonstrated that by limiting the features of transmissibility to frequency ranges of high coherence, the effect of these parameters, as compared to the effect of damage, become less significant and can be neglected for some instances. The results of additional field testing using controlled impact forces on the sacrificial specimen have reinforced the findings from the operational loading in detecting damage.