Yeast Rad1-Rad10 is a structure specific nuclease that processes branched double-strand break (DSB) repair intermediates; the persistence of which can impede normal DNA metabolism. The single strand annealing (SSA) mechanism of DSB repair acts when homologous repeats flank both sides of the DSB. End resection from the 5′ ends of the break exposes complementary sequences at the flanking repeats, which are annealed to form 3′ non-homologous flap structures. Saw1 recruits Rad1-Rad10 recruits to these 3′ non-homologous flaps, where Rad1-Rad10 incises the DNA and removes the flap. Saw1 has affinity towards branched DNA structures and forms a stable complex with Rad1-Rad10. The mechanism of both structure specific recruitment and nucleolytic activity of the Saw1-Rad1-Rad10 complex is currently unknown. To study this nuclease complex, we need to produce large quantities of pure, stable, and active recombinant protein. Using dynamic light scattering (DLS) and differential scanning fluorimetry (DSF)-based high throughput thermal stability assays, we have developed a method for large-scale production of recombinant Saw1. This optimized method has increased the stability and yield of protein, thereby allowing for future biochemical investigation of Saw1. Similarly, we have optimized the large-scale production of the higher molecular-weight complex (Saw1-Rad1-Rad10) and improved the homogeneity of the recombinant complex. We have also biochemically characterized the minimal branched DNA substrates for both Saw1 and Saw1-Rad1-Rad10. This work allows for biochemical investigation into the molecular mechanism of eukaryotic 3′ non-homologous flap removal during SSA. / Thesis / Master of Science (MSc)

Third generation advanced high-strength steels (3G-AHSS) have received significant interest from leading auto steel industries and OEMs as candidate materials for reduced mass Body In White (BIW) components due to their unique combination of high specific strength and ductility. However, the continuous hot-dip galvanizing of these steels is challenging due to selective oxidation of the main alloying elements such as Mn, Si, Al and Cr at the steel surface during the annealing step prior to immersion in the galvanizing Zn(Al, Fe) bath, as extensive coverage of the substrate surface by these oxides is detrimental to reactive wetting, good coating adhesion and integrity. Simulated galvanizing treatments were conducted on two prototype Fe-0.1C-6Mn-2Si (wt pct) 3G steels; one as the reference steel and the other with 0.05 wt pct Sn added to the composition. The combined effects of annealing temperature, time, process atmosphere oxygen partial pressure and 0.05 wt pct Sn addition on the selective oxidation of the steel substrates were determined. Subsequently, the reactive wetting of the steels with respect to the pre-immersion surface structures of the samples annealed for 120 s was examined. Annealing heat treatments were carried out at 800˚C and 690˚C in a N2-5 vol pct H2 process atmosphere under three dew points of –50˚C, –30˚C and +5˚C, covering process atmosphere oxygen partial pressures within the range of 1.20  10-27 atm to 1.29  10-20 atm. MnO was present at the outmost layer of the external oxides on all samples after annealing. However, the morphology, distribution, thickness and surface coverage were significantly affected by the experimental variables. Annealing the reference steel under the low dew point process atmospheres, i.e. –50˚C and –30˚C, resulted in the highest Mn surface concentration as well as maximum surface oxide coverage and thickness. The oxides formed under these process atmospheres generally comprised coarse, compact and continuous film forming nodules, whereas the surface morphologies and distributions obtained under the +5˚C dew point process atmosphere, which was consistent with the internal oxidation mode, exhibited wider spacing between finer and thinner MnO nodules. The grain boundary internal oxide networks had a multi layer structure with SiO2 and MnSiO3 at the oxide cores and shells, respectively. Significant morphological changes were obtained as a result of Sn addition. The continuous film-like external MnO nodules were modified to a fine and discrete globular morphology, with less surface coverage by the oxides and reduced external oxide thickness. Both the external and internal oxidations followed parabolic growth kinetics, where the depth of the internal oxidation zone decreased with Sn addition and decreasing oxygen partial pressure. Poor reactive wetting was observed for the reference steel substrates that were annealed for 120 s under the –50˚C and –30˚C dew point process atmospheres at 800˚C and under the –50˚C dew point atmosphere at 690˚C, such that no integral metallic coating was formed after the 4 s immersion in the Zn(Al, Fe) bath. By contrast, excellent coating quality was obtained for the Sn-added steels when the –30˚C and +5˚C dew point process atmospheres were employed when annealing at 690˚C. The remainder of the experimental conditions demonstrated good reactive wetting with intermediate coating quality. For the two reference steels annealed at 800˚C under the –50˚C and –30˚C dew point process atmospheres, poor reactive wetting was due to full coverage of the surface by 116 nm and 121 nm thick and continuous MnO films. In the case of the 690˚C  –50˚C reference steel with the external layer thickness of only 35 nm, however, poor wetting was attributed to substantial coverage of the surface by continuous, film-like oxides. In both cases, exposure of the underlying substrate to the bath alloy and an intimate contact between the substrate Fe and the bath dissolved Al could not take place and the formation of the Fe2Al5Znx interfacial layer was hidered. For the processing conditions that satisfactory reactive wetting was obtained despite the pre-immersion selective oxidation of the surfaces, several reactive wetting mechanisms were determined. For the samples with a sufficiently thin external MnO layer, good reactive wetting was attributed to partial reduction of MnO by the bath dissolved Al, as well as bridging of the Mn sub-oxides by the Zn coating or Fe2Al5Znx interfacial intermetallics. Partial or full formation of the Fe2Al5Znx interfacial layer was observed in the successfully galvanized substrates with Fe-Al crystals formed between, underneath and also on top of the reduced oxides. Furthermore, for cases with widely-spaced, fine oxide nodules, it was found that the liquid bath alloy was able to infiltrate the external oxide/substrate interface, resulting in surface oxide lift-off and enhanced coating adhesion. It was globally concluded that the thin, discrete and fine globular morphology of external MnO, resultant of annealing the steel substrates with 0.05 wt pct Sn addition under the process atmosphere oxygen partial pressures consistent with internal oxidation, allowed for an enhanced reactive wetting by the Zn(Al, Fe) galvanizing bath which was manifested by increased amount of Al uptake and population of the Fe2Al5Znx intermetallics at the coating/steel interface. / Thesis / Doctor of Science (PhD)

Industry 4.0 will pave the way to a new age of advanced manufacturing. Additive manufacturing (AM) is one of the leading sectors of the upcoming industrial revolution. The key advantage of AM is its ability to generate lightweight, robust, and complex shapes. AM can also customize the microstructure and mechanical properties of the components according to the selected technique and process parameters. AM of metals using selective laser melting (SLM) could significantly impact a variety of critical applications. SLM is the most common technique of processing high strength Aluminum alloys. SLM of these alloys promises to enhance the performance of lightweight critical components used in various aerospace and automotive applications such as metallic optics and optomechanical components. However, the surface and inside defects of the as-built parts present an obstacle to product quality requirements. Consequently, the post-processing of SLM produced Al alloy parts is an essential step for homogenizing their microstructure and reducing as-built defects. In the current research, various studies assess the optimal process mapping for high-quality SLM parts and the post-processing treatment of Al alloy parts. Ultra-precision machining with single point diamond turning or diamond micro fly-milling is also investigated for the as-built and post-processed Al parts to satisfy the optical mirror’s surface finish requirements. The influence of the SLM process parameters on the quality of the AlSi10Mg and Al6061 alloy parts is investigated. A design of experiment (DOE) is used to analyze relative density, porosity, surface roughness, dimensional accuracy, and mechanical properties according to the interaction effect between SLM process parameters. The microstructure of both materials was also characterized. A developed process map shows the range of energy densities and SLM process parameters for each material needed to achieve optimum quality of the as-built parts. This comprehensive study also strives to reduce the amount of post-processing needed. Thermal post-processing of AlSi10Mg parts is evaluated, using recycled powder, with the aim of improving the microstructure homogeneity of the as-built parts. This work is essential for the cost-effective additive manufacturing (AM) of metal optics and optomechanical systems. To achieve this goal, a full characterization of fresh and recycled powder was performed, in addition to a microstructure assessment of the as-built fabricated samples. Annealing, solution heat treatment (SHT) and T6 heat treatment (T6 HT) were applied under different processing conditions. The results demonstrated an improvement in microstructure homogeneity after thermal post-processing under specific conditions of SHT and T6 HT. A micro-hardness map was developed to help in the selection of optimal post-processing parameters for the part’s design requirements. A study is also presented, which aims to improve the surface characteristics of the as-built AlSi10Mg parts using shot peening (SP). Different SP intensities were applied to various surface textures of the as-built samples. The SP results showed a significant improvement in the as-built surface topography and a higher value of effective depth using 22.9A intensity and Gp165 glass beads. The area near the shot-peened surface showed a significant microstructure refinement up to a specific depth, due to the dynamic precipitation of nanoscale Si particles. Surface hardening and high compressive residual stresses were generated due to severe plastic deformation. Friction stir processing (FSP) was studied as a localized treatment on a large surface area of the as-built and hot isostatic pressed (HIPed) AlSi10Mg parts using multiple FSP tool passes. The influence of FSP on the microstructure, hardness, and residual stresses of parts was investigated. FSP transforms the microstructure of parts into an equiaxed grain structure. A consistent microstructure homogenization was achieved over the processed surface after applying a high ratio of tool pass overlap of ≥60%. A map of microstructure and hardness was prepared to assist in the selection of the optimal FSP parameters for attaining the required quality of the final processed parts. Micromachining to the mirror surface was performed using diamond micro fly-milling and single point diamond turning techniques, and the effect of the material properties on surface roughness after machining was investigated. The machining parameters were also tuned to meet IR mirror optical requirements. A novel mirror structure is developed using the design for additive manufacturing concept additive (DFAM). This design achieved weight reduction of 50% as compared to the typical mirror structure. Moreover, the developed design offers an improvement of the mirror cooling performance due to the embedded cooling channels directed to the mirror surface. A novel mirror structure is developed using the design for additive manufacturing concept additive (DFAM). This design achieved weight reduction of 50% as compared to the typical mirror structure. Moreover, the developed design offers an improvement of the mirror cooling performance due to the embedded cooling channels directed to the mirror surface. / Thesis / Doctor of Philosophy (PhD)

Additive manufacturing (AM) has the ability to fabricate components of high geometric complexity that are difficult or near impossible to be produced by traditional manufacturing technologies. Selective laser melting (SLM) is a commonly used AM technology for metallic fabrications. SLM offers the opportunities to customize the characteristics of the as-build part produced, by adjusting the laser settings. However, high strength aluminum (Al) alloys presents an obstacle for SLM production due to the low alloying content, which increases the alloys’ probabilities to form cracks due to thermal stress induced by the SLM build process. The current study focuses on the study of surface roughness and dimensional accuracy of SLM fabrication of Al6061 and AlSi10Mg. Using design of experiment (DOE), wide ranges SLM process parameters were experimented with, and their individual effect along with their interactive effects on the fabricated parts’ quality were evaluated. The quality characteristics studied are: microstructures, microhardness, tensile strength (ultimate tensile strength, and yield strength), density, surface roughness, and dimensional accuracy. Regression models were created for each quality characteristics, and the combination of density, surface roughness, and dimensional accuracy results was used to create processing window for SLM that ensures the production of high-quality parts. The work aims to not only be used as-is, to help with the selection of SLM process parameters for Al6061 and AlSi10Mg that will reduce the post- processing time, but also to set a foundation for future development for numerical models that could better predict and describe the relations between SLM process parameters and the part’s fundamental qualities. / Thesis / Master of Applied Science (MASc)

10-15% of women take antidepressants during pregnancy. Selective serotonin reuptake inhibitors (SSRIs) are most commonly used for perinatal depression. Perinatal exposure to SSRIs has been shown to disrupt the development of serotonergic signaling pathways in the central nervous system (CNS); however, the effects on the developing enteric nervous system (ENS) remain relatively unexplored. We hypothesized that early life exposure to SSRIs would influence the structural development of the gastrointestinal (GI) tract. We further hypothesized that these structural changes could lead to clinically relevant functional outcomes, such as modifications in susceptibility to inflammation and altered GI motility. Female Wistar rats were given the SSRI, fluoxetine, or vehicle from 2 weeks prior to mating through gestation until weaning. At postnatal day 1 (P1), postnatal day 21 (P21; weaning) and 6 months of age (P6 months) intestines were harvested to assess for structural changes. At P6M, intestines were collected to assess motility in vitro and subsets of the offspring were treated with dextran sulfate sodium (DSS) to assess susceptibility to colitis. At P1, there was a significant decrease in serotonergic neurons in the female colon. At P21, there was a significant increase in serotonergic neurons of both sexes in the colon. At P6M, there was a significant increase in the frequency and velocity of long-distance contractions in the colon when both sexes were combined and an increase in ZO-1 in male colon. In conclusion, SSRI exposure in utero appears to have structural and functional consequences on the developing ENS in the SSRI exposed offspring. The structural consequences are seen in both sexes at P21 and although the structural changes to the ENS resolve by 6 months, motility in the colon continues to be significantly altered. There were no significant differences in chemical colitis, however, we did see difference of quantitative mRNA cytokines, chemokines and extracellular matrix components which may suggest differences in mucosal immune response. The mechanisms by which these changes occur remain to be explored. / Thesis / Master of Science (MSc)

The main aim of this thesis is to investigate the manufacturability of different gyroid designs using Selective laser melting (SLM) process . This study paves the way for a better understanding of design aspects, process optimization, and characterization of titanium alloy (Ti6Al4V) gyroid lattice structures for bone implant applications. First, A MATLAB® code was developed to create various gyroid designs and understand the relationship between the implicit equation parameters and the measurable outputs of gyroid unit cells. A novel gyroid lattice structure is proposed, where the porosity is graded in a radial direction. Second, gyroid designs were investigated by developing a permissible design map to help choose the right gyroid parameters for bone implants. Third, response surface methodology was used to study the process-structure-property relationship and understand the effect of SLM process parameters on the manufacturability of Ti6Al4V gyroid lattice structures. Laser power was found to be the most significant factor affecting the errors in relative density and strut size of gyroid structures. A volumetric energy density between 85 and 103 J/mm3 induces the least errors in the gyroid’s relative density. Fourth, the quasi-static properties of the novel designs were compared to uniform gyroids. The proposed novel gyroids had the highest compressive strength reaching 160 MPa. Numerical simulations were studied to give insight into how manufacturing irregularities can affect the mechanical properties of gyroids. Last, an in-depth defect analysis was conducted to understand how SLM defects may influence the fatigue properties of different Ti6Al4V gyroids. Thin struts have less internal defects than thick ones; thus, they show less crack propagation rate and higher normalized fatigue life. These favorable findings contributed to scientific knowledge of manufacturability of Ti6Al4V porosity graded gyroids and determined the influence of SLM defects on the mechanical properties of gyroid designs for bone implants. / Thesis / Doctor of Philosophy (PhD) / This thesis studies the integration of design aspects, SLM manufacturability, and mechanical characterization of Ti6Al4V gyroid lattice structures used for bone implants. A MATLAB® code was developed to design novel porosity graded gyroids, and develop permissible design map to aid the choice of different gyroid designs for bone implants.. Process maps were also developed to investigate the relationship among laser power, scan speed, and the errors in the relative density of lattice structures. Moreover, the normalized fatigue strength of thin struts gyoid was found to be higher than that of thicker struts.Analytical models and finite element analysis (FEA) models were compared to experimental results. The variation of the results gives a better understanding of the effect of manufacturing defects. An improved insight of gyroids manufacturability has been obtained by integrating the permissible design space with the process-structure-property relationship, and the defect analysis of porosity graded gyroids.

Variation is inevitable in any process, so it has to be dealt with effectively and economically. Reducing variation can be achieved in assembly lines strategically and dynamically. Implementing both the strategic and dynamic variation reduction techniques is expected to lead to further reduction in the number of failed final assemblies. The dissertation is divided into three major parts. In the first part, we propose to reduce variation for assemblies by developing efficient inspection plans based on (1) historical data for existing products, or simulated data for newly developed products; (2) Monte Carlo simulation; and (3) optimization search techniques. The cost function to be minimized is the total of inspection, rework, scrap and failure costs. The novelty of the proposed approach is three-fold. First, the use of CAD data to develop inspection plans for newly launched products is new, and has not been introduced in the literature before. Second, frequency of inspection is considered as the main decision variable, instead of considering whether or not to inspect a quality characteristic of a subassembly. Third, we use a realistic reaction plan (rework-scrap-keep) that mimics reality in the sense that not all out-of-tolerance items should be scrapped or reworked. At a certain stage, real-time inspection data for a batch of subassemblies could be available. In the second part of this dissertation, we propose utilizing this data in near real-time to dynamically reduce variation by assigning the inspected subassembly parts together. In proposing mathematical models, we found that they are hard to solve using traditional optimization techniques. Therefore, we propose using heuristics.Finally, we propose exploring opportunities to reduce the aforementioned cost function by integrating the inspection planning model with the Dynamic Throughput Maximization (DTM) model. This hybrid model adds one decision variable in the inspection planning; which is whether to implement DTM (assemble the inspected subassemblies selectively) or to assemble the inspected items arbitrarily. We expect this hybrid implementation to substantially reduce the failure cost when assembling the final assemblies for some cases. To demonstrate this, we solve a numerical example that supports our findings. / Ph. D.

The subject of this dissertation is advanced inorganic membranes and their application in membrane reactors (MRs). The reaction studied is the ethanol steam reforming (ESR) reaction using Co-Na/ZnO catalysts, chosen because of their high activity and stability. The Co-Na/ZnO catalysts were prepared by a co-precipitation method and it was found that promotion with a moderate amount of Na (1.0 wt%) produced a catalyst with stable ethanol conversion and product selectivity. Higher cobalt loading, higher W:E ratio, higher reaction temperature, and lower space velocity enhanced the conversion of ethanol to H2 and CO2 while reducing the formation of undesirable acetaldehyde. Acetaldehyde was a primary product of the ESR reaction. Studies of the effect of hydrogen permeance on the ESR reaction at 623 K were performed in MRs equipped with silica-based and palladium-based membranes of different hydrogen permeances, and the highest ethanol conversion enhancement of 44 % and hydrogen molar flow enhancement of 69 % compared to a packed-bed reactor (PBR) were obtained in a MR fitted with a membrane with the highest hydrogen permeance. An operability level coefficient (OLC), defined as the ratio of the hydrogen permeation and hydrogen formation rates, was suggested as a useful tool for estimating performances of MRs for different reforming reactions such as methane dry reforming (MDR), methane steam reforming (MSR), methanol steam reforming (MeSR), and ethanol steam reforming (ESR) reactions. Studies of the effect of pressure (1-10 atm) on the ESR reaction at 623 K were carried out in a PBR and a MR fitted with a Pd-Cu membrane prepared by an electroless plating of palladium and copper at 333 K. Comparison studies showed that increasing pressure in both reactors resulted in decreasing ethanol conversions and increasing hydrogen molar flows. Compared to the PBR, higher ethanol conversions and hydrogen molar flows were obtained in the MR for all pressures studied. Increasing pressure was favorable for enhancing ethanol conversion and hydrogen molar flow in the MR compared to the PBR, and the highest ethanol conversion enhancement of 48 % with the highest hydrogen molar flow enhancement of 55 % was obtained at 10 atm in the MR. / Ph. D.

The purpose of this thesis was to assess the economic implications of an export promotion policy on poverty reduction and inter-industry growth of Ethiopia. The study was conducted in four steps. The first and the second steps involved simulation scenarios. Scenario 1 simulated the change in the incidence of poverty when FDI capital was selectively introduced into non-coffee export agriculture. Scenario 2 simulated a situation in which the coffee industry received the same policy treatment as other export agriculture in accessing FDI capital. Step three analyzed inter-industry growth under the two scenarios. In the fourth step, sensitivity analysis was conducted to assess the possible outcomes of Scenario 1 and 2 under fluctuations in world coffee prices and changes in substitution parameters. A micro-simulated CGE model was constructed to determine optimum production, income and consumption. A Beta frequency distribution function and FGT poverty measures were used to examine the changes in three household groups' income distribution and prevalence of poverty. For these analyses, the National Accounting Matrix and the Household Income and Expenditure Sample Survey data set were used. At the macro level, growth in GDP due to expansion of export agriculture was significant. But at a micro level, the magnitude and dimension of economic changes were different with respect to each policy alternative. In the selective export promotion, for instance, only rural households were able to achieve statistically significant income changes. More particularly, about 10 percent of rural households were drawn out of poverty while only 1.7 and 0.5 percent of small and large urban households overcame poverty. When export promotion was assumed to be implemented across the board of all agricultural activities, the welfare gains were extended beyond rural household groups. In this policy alternative, statistically significant mean income changes were observed for both rural and urban household members. Specifically, about 12 percent of rural, 9 percent of small urban and 5 percent of large urban households were able to escape poverty. These achievements were attributed to higher intensification of coffee production and better linkages with other industries to efficiently allocate factors of production where they provided higher rates of return. The increase in income and consumption of millions of coffee dependent households has also stimulated more agricultural and some non-agricultural productions. Simulation results were observed to deteriorate when export promotion was evaluated under world coffee price fluctuation. The negative effect of a price shock, however, was observed to be minimized under alternative an export promotion approach. / Ph. D.

First generation students face significant challenges with respect to college enrollment (Choy, 2001) and remain disproportionately underrepresented in certain segments of American higher education particularly in graduate education (Callan, 2001). Among those individuals who shape the educational plans of first-generation students are their parents (Hossler & Stage, 1999; McDonough, 1997). Researchers operationalize parental influence as the transmission of various forms of capital (Bourdieu, 1977). The purpose of this study was to determine if there was a relationship between various forms of capital parents transmit to their children and graduate school aspirations of first generation and non-first generation students attending highly selective institutions. Three dimensions of capital were explored in this study: (a) human, (b) cultural, and (c) social. Additionally, this study was designed to determine whether there are differences in the degree of these forms of capital among groups classified by race, gender and institution type. Data from the National Longitudinal Survey of Freshmen (NLSF) (Massey et. al, 2003) which included a sample of Asian, Black, Hispanic and Caucasian first year, first generation and non-first generation students from 28 highly selective colleges and universities were used for this study. The findings suggest that human, cultural, and social capital transmitted to students by parents are marginally related to graduate school aspirations regardless of generation status. Also, graduate school aspirations differ by race/ethnicity and gender, but do not differ substantively between first generation and non-first generation students in this sample. Finally, the type of institution students attend does not relate to their graduate school aspirations. / Ph. D.