Doctor of Philosophy

dissertationThe work described in this dissertation attempts to advance the science of developing semisolid microbicide products through (a) application-oriented design of drug delivery vehicles and (b) selection of HIV-specific active ingredients that yield advantage over the current antiretroviral strategies, particularly in regards to the mechanism of action through inhibition of HIV entry. Two approaches that exploit the underlying composition-structureproperty- performance relationship in polymeric systems to improve semisolid gels for the prevention of sexual transmission of HIV were explored. Firstly, an algorithm that allows de novo engineering of a delivery vehicle was developed, optimizing the composition and consequently the properties of the material to meet a predefined set of performance criteria for vaginal drug delivery. Secondly, a pH-responsive mucus-like material with the ability to attenuate the transport of virus and immune cells was engineered. Inhibition of viral transport was observed at pH above 4.8, with minimal signs of toxicity to vaginal tissue. Second part of this dissertation describes the assessment of two potent antiretroviral agents that inhibit HIV entry. The ingenuity of these agents lies in (a) the dual mechanism of HIV inhibition associated with the small molecule pyrimidinedione analogs, and (b) the design of a gp120 targeted macromolecular therapeutic that is synthetic in nature and shows activity comparable to that of iv the protein-based lectins. Hydroxyethyl cellulose gels formulated with 0.25 w% pyrimidinedione analog showed activity at ~ 14 ug/mL in an in vitro antiviral assay. In the design of gp120 targeted synthetic lectins, benzoboroxole showed weak affinity for nonreducing sugars; however, it demonstrated antiviral activity at nanomolar concentrations when incorporated into high molecular weight polymers. Activity increased with increasing degree of functionalization and molecular weight of the polymer. Supplementing the polymer backbone with sulfonic acid increased its aqueous solubility in addition to a synergistic increase in antiviral activity. These strategies support the paradigm shift from use of generic semisolid drug delivery systems to a performance-based design of polymeric materials for vaginal drug delivery. Furthermore, formulating semisolid systems to deliver antiretroviral agents, such as the pyrimidinediones or the synthetic lectins, may provide a versatile microbicide candidate that is potent, affordable and nontoxic

Solving Multi-objective Integer Programs using Convex Preference Cones

Esta encuesta tiene dos objetivos: en primer lugar, identificar a los individuos que fueron víctimas de algún tipo de delito y la manera en que ocurrió el mismo. En segundo lugar, medir la eficacia de las distintas autoridades competentes una vez que los individuos denunciaron el delito que sufrieron. Adicionalmente la ENVEI busca indagar las percepciones que los ciudadanos tienen sobre las instituciones de justicia y el estado de derecho en Méxic

Enhancing the Environmental Sustainability of the Production and Degradation of PHA Polymers

The negative impacts caused by traditional plastics to natural ecosystems are becoming increasingly drastic. One solution to this issue is greater implementation of polyhydroxyalkanoates (PHAs), which are biodegradable plastics naturally produced by bacteria. The primary objective of this work was to exemplify and add to the body of research being conducted to further progress the PHA industry as a whole. Economic feasibility is a major barrier preventing broader usage of PHAs, therefore a study was performed to create a novel method for engineering Halomonas bacteria, a highly attractive genus for its potential in lowering PHA production costs. To ensure environmental compatibility, research was conducted to investigate the natural biodegradation of PHA polymers and determine how some naturally present microorganisms metabolize components of these materials. The insights provided by these studies will further promote our ability to expand PHA technologies while maintaining a focus on environmental sustainability

Revitalizing Brands and Brand Portfolios: Essays on Brand and Brand Portfolio Management Strategies

How should consumer products manufacturers and retailers keep their portfolio of brand offerings relevant and energetic when large numbers of new brands are continuously launched into a world of increasingly nonloyal customers with evolving needs? The harsh reality is, at a time when the demise of old brands has accelerated and even established brands are vulnerable, it stands to be a great deal of challenge. Fortunately, a number of ‘revitalization’ strategies can add relevance and energy to brands and brand portfolios. This dissertation comprises three essays each of which explores the outcomes of a commonly utilized revitalization strategy. In Chapter 2 and Chapter 3, strategies involving simplification of brand offerings are at the center of interest. Chapter 4 departs from these chapters in that it focuses on sponsorship, a widely utilized external brand energizer. The essays included in this dissertation show that companies can revitalize their offerings to maintain growth even in proliferating environments. My findings collectively lay out the importance of pursuing a portfolio approach to achieve greater success in executing revitalization strategies. Firms should acquire a thorough understanding of how their revitalization efforts can be linked to the performance of each brand in their portfolio by carefully considering individual brands’ roles and their relationships with one another

A technique for calculating atmospheric scattering and attenuation effects of aerial photographic imagery from totally airborne acquired data

Image degradation of color aerial photography due to atmospheric effects is spectrometrically evaluated as a function of air column depth for the purpose of defining corrective terms for the conditions under which the particular imagery was acquired. The theoretical development illustrates how these terms may be used to \u27subtract out\u27 the atmospheric effects of back-scatter and attenuation from the imagery. The technique suggests that true spectral information of ground objects can be calculated despite the presence of atmospheric effects during aerial photo graphic data collection. To determine the validity of the technique, the totally airborne method results are compared to results by methods which employed ground truth information