No description available.

No description available.

No description available.

Neurodegenerative diseases are characterized by selective neuronal vulnerability and subsequent degeneration in specific areas of the brain. Huntington’s Disease (HD) is inherited as an autosomal dominant mutation that primarily affects the cells of the striatum and the cerebral cortex, leading to a triad of symptoms that include the progressive loss of motor function, defects in cognitive ability and psychiatric manifestations. HD is caused by a CAG repeat expansion that exceeds 37 repeats in Exon1 of the ​HTT​ gene, manifesting as a pathogenic polyglutamine (polyQ) amino acid tract expansion in the huntingtin protein. HD is a late onset disorder, with disease onset around 40-50 years of age and symptoms that worsen over 10-20 years. Only a few symptomatic treatments are available and there is currently no cure for the disease. Therapeutics to target the huntingtin gene itself have only been in clinical trial in the past 2 years. The length of the expansion has an inverse relationship with the age of disease onset. Most patients that have repeats between 40-45 CAG, however, have varying age of disease onset. Recent genome-wide association studies (GWAS) have implicated DNA handling and repair pathways as modifiers of age of disease onset up to 6 years. Therapeutic approaches to modify and delay onset indefinitely through other genetic targets will require identification of pathological mechanisms that precede disease onset. Several hallmark phenotypes have been identified in cell and animal models, including pathogenic aggregate formation. These models are not reflective of human biology, using excessively large CAG repeats (>100) associated with the more aggressive, juvenile HD, overlooking the importance of GWAS results and the progression of disease with lower pathogenic CAG repeats (40-50 CAG). We have therefore generated novel, clinically-relevant human patient fibroblast cell lines and have characterized several disease phenotypes. My thesis presents a culmination of several projects that focus on disease modelling, primarily outlining phenotypic differences between wildtype and HD cells that will benefit our understanding of disease pathogenesis. / Thesis / Doctor of Philosophy (PhD)

This dissertation explores mathematical programming optimization models and algorithms for routing and scheduling ships in a maritime transportation system. Literature surveyed on seaborne transportation systems indicates that there is a scarcity of research on ship routing and scheduling problems. The complexity and the overwhelming size of a typical ship routing and scheduling problem are the primary reasons that have resulted in the scarcity of research in this area. The principal thrust of this research effort is focused at the Kuwait Petroleum Corporation (KPC) Problem. This problem is of great economic significance to the State of Kuwait, whose economy has been traditionally dominated to a large extent by the oil sector. Any enhancement in the existing ad-hoc scheduling procedure has the potential for significant savings. A mixed-integer programming model for the KPC problem is constructed in this dissertation. The resulting mathematical formulation is rather complex to solve due to (1) the overwhelming problem size for a typical demand contract scenario, (2) the integrality conditions, and (3) the structural diversity in the constraints. Accordingly, attempting to solve this formulation for a typical demand contract scenario without resorting to any aggregation or partitioning schemes is theoretically complex and computationally intractable. Motivated by the complexity of the above model, an aggregate model that retains the principal features of the KPC problem is formulated. This model is computationally far more tractable than the initial model, and consequently, it is utilized to construct a good quality heuristic solution for the KPC problem. The initial formulation is solved using CPLEX 4.0 mixed integer programming capabilities for a number of relatively small-sized test cases, and pertinent results and computational difficulties are reported. The aggregate formulation is solved using CPLEX 4.0 MIP in concert with specialized rolling horizon solution algorithms and related results are reported. The rolling horizon solution algorithms enabled us to handle practical sized problems that could not be handled by directly solving the aggregate problem. The performance of the rolling horizon algorithms may be enhanced by increasing the physical memory, and consequently, better solutions can be extracted. The potential saving and usefulness of this model in negotiation and planning purposes strongly justifies the acquisition of more computing power to tackle practical sized test problems. An ad-hoc scheduling procedure that is intended to simulate the current KPC scheduling practice is presented in this dissertation. It is shown that results obtained via the proposed rolling horizon algorithms are at least as good, and often substantially better than, results obtained via this ad-hoc procedure. / Ph. D.

The most thermodynamically stable biological structure is the cross-beta secondary structure of the "amyloid"or "prion". As a testament to its stability, the amyloid occurs naturally in 2 rare instances: as a mechanism to protect or destroy life. Pathogenic amyloids are the signature of neurological disorders such as Alzheimer's and Parkinson's disease and bovine spongiform encephalopathy (BSE), which have no effective treatments or known cures. Pathogenic amyloids appear as nanometer sized "plaques" that self-assemble over time. The plaques usually are well-organized crystalline/fibrous structures ~10-20 nm in diameter and >100 nm long. "Functional" amyloids are very rare in nature and serve the direct purpose to proliferate life. Stalks to protect eggs, fibers to coat spores, and adhesive proteins of bacteria, algae, fungi, and mollusks are examples. Functional amyloids can be larger than pathogenic amyloids by 1-2 orders of magnitude. There is a burgeoning research field based on emulating the amyloid. This is because it can be formed from a host of proteins or peptides simply by denaturing them enough to form a cross-beta secondary structure and has a modulus of >10 GPa. As a general reference, "protein" is usually a very high molecular weight, naturally occurring molecule and "peptide" is a much smaller portion of a natural protein or a non-natural molecule synthesized from a few amino acids. Researchers are increasingly attempting to take advantage of the functional amyloid. It is still not understood how the functional amyloid self-assembles or why it can be larger than the pathogenic amyloid. We have identified a potential pathway to large functional amyloids that involves a long alpha-helix containing protein (the "adder") undergoing an alpha to beta transition in the presence of a hydrophobic beta-sheet template. Testing our hypothesis against proteins found in natural large functional amyloids seems to suggest it is a ubiquitous process. The resulting material is a fiber composite similar to the native structures. / Master of Science

Synthetic nanomagnetite has been suggested as a potential reactant for the in-situ treatment of contaminated groundwater. Although the application of nanomagnetite for environmental remediation is promising, a full understanding of its reactivity has been deterred by the propensity of the nanoparticles to aggregate and form clusters. To characterize the factors responsible for this aggregation behavior, we determined the magnetic properties of magnetite using a superconducting quantum interference device (SQuID). Importantly, because magnetite readily reacts with O2 to produce maghemite, we analyzed the effect of oxidation on its magnetic properties. We observed that oxidation caused a decrease in the saturation magnetization and the anisotrophic barrier of magnetite resulting in less significant magnetic interactions between particles. Consequently, a decrease in the aggregation of magnetite clusters and a potential increase in stability are expected after oxidation. To support these findings, an extended series of experiments to measure the aggregation and the sedimentation of clusters of unoxidized and oxidized magnetite nanoparticles were conducted. Although the individual particle diameter remained constant after oxidation, the cluster size and the aggregation and sedimentation kinetics of magnetite were determined to be different. Oxidized samples of magnetite tended to have lower aggregation rates and were more resistant to sedimentation. These findings can be used to have a better understanding of the overall fate, transport, and reactivity of nanomagnetite, and to gain new insights on its role as a remediation agent in the subsurface environment. / Ph. D.

The purpose of this thesis is to explore the concept of resource scheduling and pricing and its relation to carrier aggregation. The first main topic is a modified Frank Kelly algorithm that allows for the use of utility functions that are piecewise concave, but not a member of a strictly \'diminishing return\' model. This adjustment to the Frank Kelly algorithm allows resource allocation to take into account devices with multiple applications. The second topic introduces the idea of scheduling resources in a carrier aggregation scenario assuming the carriers are scheduled sequentially. / Master of Science

Keratin is a biomaterial derived from biological sources and can be used in a variety of medical applications. This study focuses on keratin derived from human hair. Unfortunately, there is not a lot of information in the literature describing how keratin reacts to subtle changes in an aqueous solution such as differences in pH, keratin concentration, buffer concentration, salt concentration, and temperature. To have a better understanding of this effect, dynamic light scattering was used to test the size ranges and volume percentages in each range. Dynamic light scattering shows the size of the keratin in each environment and its consistency with time. The results showed that there is a difference in keratin behavior between water and buffer solutions, but very subtle differences between each buffer, buffer concentration, keratin concentration, pH and temperature. Keratins aggregate extensively in un-buffered conditions (i.e. pure water), which has implications to both purification and fabrication of biomaterials as water is used extensively in these processes. Interestingly, there was little effect of keratin concentration, pH, and temperature on the buffers used in this study, suggesting there may be a wide range of conditions in which aggregation can be minimized. / Master of Science

Yes / Against a background of the low engagement of SMEs in e-business this paper investigates the emergence of, and potential for, critical e-applications defined as `an e-business application, promoted by a trusted third party, which engages a significant number of SMEs by addressing an important shared business concern within an aggregation.¿ By a review of secondary data and empirical investigation with service providers and other intermediaries the research shows that such applications can facilitate the e-business engagement of SMEs. There are three key findings, namely: the emergence of aggregation specific e-business applications; the emergence of collaboratively based `one to many¿ business models; and the importance of trusted third parties in the adoption of higher complexity e-business applications by SMEs. Significantly this work takes a deliberately provider perspective and complements the already considerable literature on SME IT adoption from a user and network perspective. In terms of future research the importance of a better conceptual understanding of the impact of complexity on the adoption of IT by SMEs is highlighted.