This thesis focuses on task sequencing and manpower scheduling to develop robust schedules for an aircraft manufacturer. The production of an aircraft goes through a series of multiple workstations, each consisting of a large number of interactive tasks and a limited number of working zones. The duration of each task varies from operator to operator, because most operations are performed manually. These factors limit the ability of managers to balance, optimize, and change the statement of work in each workstation. In addition, engineers spend considerable amount of time to manually develop schedules that may be incompatible with the changes in the production rate. To address the above problems, the current state of work centers are first analyzed. Then, several deterministic mathematical programming models are developed to minimize the total production labour cost for a target cycle time. The mathematical models seek to find optimal schedules by eliminating and/or considering the effect of overtime on the production cost. The resulting schedules decrease the required number of operators by 16% and reduce production cycle time of work centers by 53% to 67%. Using these models, the time needed to develop a schedule is reduced from 36 days to less than a day. To handle the stochasticity of the task durations, a two-stage stochastic programming model is developed to minimize the total production labour cost and to find the number of operators that are able to work under every scenario. The solution of the two-stage stochastic programming model finds the same number of operators as that of the deterministic models, but reduces the time to adjust production schedules by 88%.

DNA post-replication repair (PRR) is a cellular tolerance mechanism by which eukaryotic cells survive lethal lesions during or after DNA synthesis. In the yeast Saccharomyces cerevisiae, modification of proliferating cell nuclear antigen (PCNA) by ubiquitin and by small ubiquitin-like modifier (SUMO) plays an important role in PRR. PCNA ubiquitination is dependent on Rad6, a ubiquitin-conjugating enzyme (E2) and Rad18, a ubiquitin ligase (E3). Rad6 and Rad18 form a stable complex. PCNA sumoylation is dependent on Ubc9, an E2 specific to SUMO modification. <p>PRR in mammalian cells is less well understood. However, human Rad18 (hRad18) has been found to interact with human Rad6 (HHR6A/B). In this study, we detected physical interaction between hRad18 and human Ubc9 (hUbc9) through yeast two-hybrid assays. In order to define the domain(s) of hRad18 involved in the formation of a complex with HHR6B or hUbc9, a series of yeast two-hybrid constructs containing various hRAD18 gene deletions and mutations were made. A C-terminal region of hRad18, containing the putative HHR6A/B binding domain (amino acids 340 to 395), interacts with HHR6A/B while the N-terminus (amino acids 1-93) does not. Yeast Rad18 has a homologous fragment of the HHR6A/B binding domain and this fragment is sufficient to interact with yeast Rad6 in yeast two-hybrid assays, so we infer that hRad18 interacts with HHR6B through the same domain. Surprisingly, both the N-terminal and C-terminal fragments of hRad18 can interact with hUbc9, suggesting the existence of two separate domains in hRad18 interacting with hUbc9. The N-terminal fragment of hRad18 contains only a RING finger domain (amino acids 25-64), which is probably responsible for binding to hUbc9. The C-terminal fragment of hRad18 with HHR6A/B binding domain deletion can still interact with hUbc9, suggesting that the HHR6A/B binding domain is not involved in hUbc9 interaction. A key cysteine mutation (C28F) in the RING finger domain abolished the interactions of hRad18 with both HHR6A/B and hUbc9. This amino acid substitution is likely to alter the three-dimensional structure of the protein, thus making the protein unstable. Taken together, results obtained from this study suggest that hRad18 may regulate the modification status of PCNA by interacting with two different E2s, HHR6A/B and hUbc9, through distinct domains.

The purpose of this project was to produce visual work that examined a possible nostalgia that unfolds around the breakfast meal. The method of examination involved creating a process breakfast that was followed thirty times. The result of following this process was the taking of three hundred Polaroids that were then edited for their potential to visually reconstruct the ideal process breakfast. This process of discovery has resulted in a number of significant insight into the narrative of breakfast: that an idealized narrative could exist in the visualization of the process breakfast; that elements of nostalgia that may exist within the work are contingent on the viewer; and the level of authenticity of the project affects the nature of the idealization in effect.

The goal of this research is to understand how three different parameters affect single chain variable fragment (scFv) binding capacity. The parameters that were varied include the number of variable complementarity determining regions (CDRs), the number amino acids used to diversify CDRs, and configuration of the structure. How the parameters affect the binding capacity will be tested using the yeast two hybrid assay against five different protein domains. Eight scFv libraries were generated; the genes expressing the scFvs were constructed and the CDRs were randomized using PCR amplification. Genes expressing scFvs were cloned, using the homologous gap repair mechanism in <i>Saccharomyces cerevisiae</I>. Representative members of scFv libraries were sequenced to confirm correct construction.<p> Library diversity was calculated from the library transformation efficiency. Transformation efficiency refers to the number of cells that grew at the time of transformation of the scFv gene into yeast cells. There were significant differences in the diversity of the scFv libraries, which created difficulty in comparing the library binding capacities. Sequencing the scFv libraries revealed that on average 50% of each library contained correct scFv sequences. The percent of correct sequences within each library was then used to calculate the functional diversity.<p> The yeast two-hybrid assay was used to screen the scFv libraries for interactions and to test binding capacity. The binding capacity of the scFv libraries was tested and compared in five different yeast two-hybrid assays using five protein domains as the targets for each screen. The screening results showed that in all cases cyclic scFv libraries had a statistically significant higher binding capacity than linear scFv libraries despite a diversity bias against the cyclic libraries. There was no clear trend in binding capacity with the other two parameters; however, the four amino acid three CDR libraries dominated over the other libraries in almost every screen.<p> Some of the scFvs isolated from the screens were expressed in <i>E. coli</i> and <i>S. cerevisiae</i>to analyze for proper expression and correct size. All the scFvs that were isolated and analyzed were the correct size and could be purified using a poly histidine tag.<p> Due to its bioaffinity and specificity, scFvs were constructed to profile disease patterns, and to identify potential drug targets. In addition to its original application to health-related studies, scFvs could also be extended to locate potential metabolic bottlenecks, to alter metabolic flux to enhance productivity, and regulate metabolic bionetworks. Industrial microorganisms are generally carrying more than two sets of chromosomes, making it difficult to be genetically engineered when conventional approaches are employed. With the availability of scFvs as reported in this thesis, we are able to design specific scFvs that selectively bind to target proteins, resulting in re-routing of metabolic flux within the microorganism, toward a high productivity of desired product. ScFvs can be applied to industrial microorganisms directly, leading to the development of new fermentation processes.

Astrocytes, the major type of non-neuronal cells in the brain, play an important functional role in the brains extracellular potassium (K+) and pH homeostasis. Pathological brain states have been shown to cause astrocyte swelling. However, these volume changes have never before been verified to occur in response to physiological activity. In the present thesis, two-photon laser scanning microscopy was used to visualize real-time astrocyte volume changes in the stratum radiatum of the CA1 region of the hippocampus. Astrocyte somas and primary processes were observed to swell by 19.0±0.9% in response to a physiological (3 mM) increase in the concentration of extracellular K+. Astrocyte swelling was partially mediated by K+ influx through inwardly rectifying K+ channels (Kir), as their inhibition resulted in a significant decrease of the increased K+ induced astrocyte swelling (13.9±0.9%). In addition, the bicarbonate ion (HCO3-) was found to play a significant role in the increased K+ induced astrocyte swelling. The astrocyte swelling was significantly decreased when the influx of HCO3- was decreased in 1) a HCO3- free extracellular solution (5.4±0.7%), 2) in the presence of an extracellular carbonic anhydrase inhibitor (11.4±0.6% ), and 3) when the activity of the sodium-bicarbonate cotransporter (NBC) was blocked (8.3±0.7%) . Conversely, astrocytes were found to shrink by 7.7±0.5% in response to ã-Amino-butyric Acid (GABA) receptor activation. GABAA receptor mediated astrocyte shrinkage was significantly decreased to 5.0±0.6% when HCO3- efflux was reduced. Furthermore, in this thesis it was shown for the first time that astrocytes swell in response to neuronal stimulation (4.0±0.4%). This activity induced astrocyte swelling was significantly decreased to 1.5±0.2% in a HCO3- free extracellular solution. These astrocyte volume changes may have important implications for the regulation of brain activity under both physiological and pathological brain states.

An advanced ascent guidance algorithm for rocket-powered launch vehicles is developed. The ascent guidance function is responsible for commanding attitude, throttle and setting during the powered ascent phase of flight so that the vehicle attains target cutoff conditions in a near-optimal manner while satisfying path constraints such as maximum allowed bending moment and maximum allowed axial acceleration. This algorithm cyclically solves the calculus-of-variations two-point boundary-value problem starting at vertical rise completion through orbit insertion. This is different from traditional ascent guidance algorithms which operate in an open-loop mode until the high dynamic pressure portion of the trajectory is over, at which time there is a switch to a closed loop guidance mode that operates under the assumption of negligible aerodynamic forces. The main contribution of this research is an algorithm of the predictor-corrector type wherein the state/costate system is propagated with known (navigated) initial state and guessed initial costate to predict the state/costate at engine cutoff. The initial costate guess is corrected, using a multi-dimensional Newtons method, based on errors in the terminal state constraints and the transversality conditions. Path constraints are enforced within the propagation process. A modified multiple shooting method is shown to be a very effective numerical technique for this application. Results for a single stage to orbit launch vehicle are given. In addition, the formulation for the free final time multi-arc trajectory optimization problem is given. Results for a two-stage launch vehicle burn-coast-burn ascent to orbit in a closed-loop guidance mode are shown. An abort to landing site formulation of the algorithm and numerical results are presented. A technique for numerically treating the transversality conditions is discussed that eliminates part of the analytical and coding burden associated with optimal control theory.

Galaxies and clusters of galaxies are believed to be dominated by non-luminous non-baryonic dark matter. A favored candidate is a new type of Weakly Interacting Massive Particle (WIMP) with a mass of order 100 GeV/c^2. The ZEPLIN II experiment is a WIMP search experiment that attempts to directly detect WIMP interactions using the two-phase xenon approach. The detector measures both scintillation and ionization generated by interactions in a 31 kg liquid xenon target. This approach provides a powerful discrimination between nuclear recoils, as expected from WIMPs, and background electron recoils. In this work, we develop a new X^2 approach to determine the three dimensional event positions in an attempt to improve the background rejection. The optical properties of the PTFE reflectors and the grids of the detector were determined using the Geant4 simulation, and event positions were obtained by finding the best match to the amount of light in each photomultiplier. This was found to greatly improve the position resolution. The approach was then applied to the WIMP search data. It was found that one of the dominating background sources was events from the gas above the anode grid and not from the PTFE walls caused by the small signals as previously thought. WIMP search results were then obtained from the first 31 days of stable ZEPLIN II data using two methods. Although the X^2 method greatly improved position resolution, the number of background events was not significantly altered and the new limit agreed well with the limit published by the collaboration.

Liquid-metal Rankine power conversion systems (PCS) coupled with a fission reactor remain an attractive option for space power applications because system specific power and efficiency is very favorable for plant designs of 100 kW(e) or higher. Potential drawbacks to the technology in a reduced gravity environment include two-phase fluid management processes such as liquid-vapor phase separation. The most critical location for phase separation is at the boiler exit where only vapor must be sent to the turbine because blade erosion occurs from high velocity liquid droplets entrained by vapor flow. Previous studies have proposed that rotary separators be used to separate the liquid and vapor from a two phase mixture. However these devices have complex turbo machinery, require kilowatts of power and are untested for high vapor flow conditions. The Interphase Transport Phenomena (ITP) laboratory has developed a low-power, passive microgravity vortex phase separator (MVS) which has already proven to be an essential component of two-phase systems operating in low gravity environments. This thesis presents results from flight experiments where a Rankine cycle was operated in a reduced gravity environment for the first time by utilizing the MVS for liquid and vapor phase separation. The MVS was able to operate under saturated conditions and adjust to system transients as it would in the Rankine cycle by controlling the amount of liquid and vapor within the device. A new model is developed for the MVS to predict separation performance at high vapor flow conditions for sizing the separator at the boiler, condenser, and turbine locations within the cycle by using a volume limiting method. This model factors in the following separator characteristics: mass, pumping power, and available buffer volume for system transients. The study is concluded with overall Rankine efficiency and performance changes due to adding vortex phase separation and a schematic of the Rankine cycle with the integration of the MVS is presented. The results from this thesis indicate the thermal to electric efficiency and specific mass of the cycle can be improved by using the MVS to separate the two phases instead of a rotary separator.

The purpose of this study was to examine perceptions of possible factors that lead to academic success for African American children who participated in two-way immersion programs. In order to examine the perceptions, the following areas were explored: 1.) The evolution of the academic achievement gap that exists between African American and Anglo children and the reasons theorists gave as to why the gap exists, as well as the importance of this connection to two-way immersion program participation 2.) The evolution of the modern two-way immersion language program via its development through bilingual education, and 3.) The development of Canadian twoway immersion language programs, and how political, economic, and cultural factors have impacted their successful implementation. The research method consisted of purposeful sampling of six African-American children in fourth and fifth grade who are participants in an elementary two-way immersion language program and their primary caregivers. The interviews were audio taped with notes taken for clarity. The data revealed that the primary caregivers perceived the participation of their children in a two-way language immersion program to be an educational move which would enhance the lives of their children economically, educationally and socially. The primary caregivers maintained involvement in the education of their children through facilitating homework completion in Spanish, communicating with teachers on a regular basis, participating in PTO, and facilitating structured and unstructured extra curricular activities with family and friends. The children perceived positive teacher interaction to play an important role in their academic success. They had positive experiences speaking Spanish with friends, family, and persons that they did not know. The primary caregivers perceived that the school and the district did not provide enough additional support to facilitate Spanish language acquisition for their children. This would indicate that more support from the school and the district is needed for future groups of African-American children in two-way immersion language programs.

In this dissertation we used tunable particle-particle and particle-substrate attraction to achieve reversible two-dimensional crystallization of colloids on homogeneous and patterned substrates. Total internal reflection and video microscopy techniques were used to quantify the interparticle and particle-substrate interactions in these colloidal systems. Equilibrium and dynamic simulations were then utilized to link these colloidal interactions to the experimental colloidal phase behaviour. The importance of the nature of the attractive interaction in successfully crystallizing colloids has also been documented. The first set of experiments demonstrates the use of temperature and specific ion effects to reversibly control the net particle-substrate van der Waals (vdW) attraction. Colloidal stabilization was achieved via the use of adsorbed polymer brush layers. By using evanescent wave microscopy, we directly and precisely measured how temperature and specific ion effects control the dimensions of adsorbed polymer layers and hence the net van der Waals attraction in between the colloids and the substrate. However, the magnitude of the van der Waals attraction decays very rapidly with increasing surface separation and is therefore not conducive to the self assembly of colloidal crystals. We successfully used thermoresponsive polymer nanoparticles to control the depletion attraction between micron sized silica particles and thereby induced reversible crystallization of the micron sized silica colloids on homogeneous substrates. Video and evanescent wave microscopy techniques were used to measure the nanoparticle-induced attractive interaction as a function of temperature. The experimentally observed phase behaviour was verified via simulations that utilized knowledge of the measured colloidal depletion interactions. Finally, patterned surface topologies were used to position attractive colloidal crystals. Simulations were used to link the measured colloidal interactions to experimental phase behaviour as well as substrate topology. An extension of the concepts developed in this dissertation might suggest a general strategy to assemble colloidal particles into robust and annealable crystals contributing to the fabrication of photonic bandgap materials.