published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Master of Philosophy

published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

The influence of the size and morphology of carrier particles on drug dispersion performance from passive dry powder inhalers has been extensively studied topic, and a consensus has been reached regarding the adverse effect that larger carrier particle diameters impart to aerosol performance. However, previous studies have generally employed only a few carrier particle size fractions, generally possessing similar surface characteristics. Accordingly, theories developed to explain the influence of the physical characteristics of carrier particles on performance relied heavily on both extrapolation and interpolation. To fill in the gaps from the literature and simultaneously evaluate the influence of carrier particle size and morphology, a comprehensive study was undertaken using 4 lactose grades, each sieved into 13 contiguous sizes, to prepare 52 formulations incorporating a unique lactose grade-size population. The aerosol performance results indicated that large carrier particles possessing extensive surface roughness can improve drug dispersion, in contrast to what has been previously reported. It is proposed that this may be attributed to mechanical detachment forces arising from collisions between the carrier particle and inhaler during actuation. Based on these observations, a novel dry powder inhaler platform was developed, employing carrier particles much larger (> 1 mm) than previously explored in both the scientific and patent literature. Optimization of this technology required the judicious selection of a carrier material, and following an extensive screening process, low-density polystyrene was selected as a model candidate. Given its low mass, diameters in excess of 5-mm could be employed as carriers while still generating high detachment forces. To minimize drug particle aggregation, a novel drug-coating method employing piezo-assisted particle dispersion was developed to compensate for the reduced surface area of the novel carrier particles. In addition, the selection of a suitable inhalation device prototype was instrumental to the overall performance of the technology. In vitro testing of the novel large carrier particles yielded emitted fractions in excess of 85%, and overall drug delivery of up to 69% of the nominal dose. / text

Polyketide biosynthesis is a field that has had tremendous advances in the past 50 years. The understanding of the mechanisms is updated as investigations delve into domain interactions of these microbial natural products. Although numerous polyketides are known, similarities in the sequence of product generation can be used as templates for further exploration of enzymatic activity. The focus of studies recently has been towards developing protocols to manipulate the natural products resulting in medicinally important manufactured products. This investigation examined the mechanism of the acyl carrier protein (ACP) module involved in biosynthesis. / text

In Chapter 1, I analyze a setting where a pair of retailers which sell unrelated products at the same location (e.g., a strip mall) compete with other retailers located at a different strip mall across town by jointly introducing a bundling discount while independently setting their respective stand-alone prices. Customers who shop from multiple strip malls rather than only one incur additional exogenous shopping costs. I first show that if each retailer chooses a bundling discount non-cooperatively, then the equilibrium bundling discounts will be zero. In contrast, pairs of firms located at the same strip mall always find it profitable to jointly offer positive bundling discounts in order to encourage customer loyalty. Moreover, I demonstrate as a comparative static that as the shopping costs increase, pairs of firms have less incentive to make joint bundling arrangements in equilibrium. If only one pair can introduce a bundling discount, in equilibrium while total industry profit rises, consumer surplus and welfare fall with the increase in shopping costs. When both pairs offer the bundling discounts, all consumers buy a bundle in equilibrium. Thus, the presence of a positive shopping cost does not affect any industry variables in equilibrium except stand-alone equilibrium prices which decrease with the shopping costs so that the standard Hotelling result extends to this case. In Chapter 2, I investigate the effects of shopping costs on the merger incentives of these unrelated retailers in the context of bundling. I demonstrate that contrary to one’s initial conjecture, pairs of firms do not merge to internalize the externalities created by shopping costs and bundling discounts. While consumers are better off with the merger outcome, consumer and total welfare fall significantly when firms stay independent in equilibrium. In Chapter 3, I analyze how legacy carriers and Southwest Airlines respond to the threat of AirTran Airways entry. My estimation results suggest that equilibrium prices of legacy carriers are on average lower in response to the threat of entry by AirTran as expected, whereas those of Southwest are on average higher. This robust result on AirTran and Southwest competition echoes the pricing behavior in the pharmaceutical industry where brand-name prices increase before and after generic entry. The incumbent low cost carrier Southwest, especially with the incapability to further lower its prices significantly, may still find it profitable to capitalize on its loyal price-inelastic (i.e., high-end) customers. Anticipating a definite price cut from AirTran, however, the high-end customers of legacy carriers may be more sensitive to price differentials offered by AirTran relative to the high-end customers of Southwest because of the size of the offer. Hence, legacy carriers, in contrast, simply reduce their prices in response to threat of AirTran entry to keep these valuable customers. / text

published_or_final_version / abstract / Botany / Master / Master of Philosophy

published_or_final_version / abstract / toc / Molecular Biology / Master / Master of Philosophy

Inertial sensors and magnetometers are often used for attitude determination of moving platforms. This thesis treats an alternative method; GPS-based attitude determination. By using several GPS-antennas, and with carrier phase measurements determining the relative distance between them, the attitude can be calculated. Algorithms have been implemented in Matlab and tested on real data. Two commercial GPS-based attitude determination systems have also been tested on a mobile platform and compared to a navigation grade Inertial Navigation System (INS). The results from the tests show that GPS-based attitude determination works well in open areas, but would require support from additional sensors in urban and forest environments.

The splotch (sp) mutation has been identified as a mutation in the paired box gene, Pax-3. Heterozygous mice carrying this mutation are phenotypically normal, with the exception of a white spot on their bellies. Homozygous embryos do not live to birth, and suffer from a wide range of developmental defects, all of which result from delayed neural tube closure, or inadequate neural crest cell migration. Most notably, homozygotes have an increased rate of spina bifida with or without exencephaly. Retinoic acid (RA), which has been shown to be very important in the development of a number of systems, was shown to cause a selective mortality of the homozygous splotch embryos when administered maternally at day 9 p.c. (Moase and Trasler, 1987). Since cellular retinoic acid binding protein (CRABP) is localized to the tissues which are affected by both the splotch gene, and retinoic acid teratogenesis, its expression patterns in the developing splotch embryo were examined. It was found that the distribution of CRABP mRNA is normal, but its expression levels are excessive in splotch homozygous day 9 mouse embryos.