Cell-based insulin therapies can potentially improve glycemic regulation in insulin dependent diabetes patients and thus help reduce secondary complications. The long-term goal of our work is to engineer autologous insulin-secreting intestinal endocrine cells as a non-beta cell approach to alleviate donor cell shortage and immune rejection issues associated with islet transplantation. These cells have been chosen for their endogenous similarity to beta cells, but generating cell constructs with sufficient insulin secretion for therapeutic effect has proven challenging. Previous work in our lab showed that a tissue engineered pancreatic substitute (TEPS) based on an engineered insulin-secreting L cell line, GLUTag-INS, was insufficient in affecting blood glucose levels in streptozotocin-induced diabetic mice, but promising since human insulin was detected in the blood. The objective of this project was therefore to fabricate an improved TEPS based on GLUTag-INS cells and evaluate its suitability as a standalone diabetes therapy. To achieve this objective, the following specific aims were (1) to investigate gene incorporation as a strategy to enhance recombinant insulin secretion from GLUTag-INS cells; (2) to develop and characterize a TEPS in vitro based on a microcapsule system containing improved GLUTag-INS cells with bioluminescence monitoring capability; and (3) to assess therapeutic efficacy of the graft in a diabetic, immune-competent mouse model and use bioluminescence monitoring to elucidate in vivo transplant behavior. This thesis therefore reports on the progression of studies from the genetic and molecular levels for improved insulin secretion per-cell, to the tissue level for enhanced secretion per-graft, and lastly to the preclinical level for therapeutic assessment in a diabetic mouse model.

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Large infected bone defects (IBD) are very complicated to treat due to their high variability; they often require multiple procedures. Bone autografts are the gold standard for treatment but have several drawbacks, such as a need for a second surgery site, limited grafting material, and donor site morbidity. The objective of this research was to develop a moldable synthetic bone grafting material capable of releasing both antimicrobial and osteogenic drugs over a clinically relevant time course for the treatment of IBDs. Current treatment methods for large IBDs require two separate procedures to treat the bone defect and the infection. This research sought to combine these two procedures into one implantable composite bone graft substitute for the treatment IBDs. To begin, the degradation and mechanical properties of the calcium sulfate (CS) based composite material were evaluated for different compositions. Next, the controlled drug release profiles from the composite was achieved by using a shell and core system incorporating poly(lactic-co-glycolic acid) microspheres (PLGAms). The release of vancomycin from the shell began immediately and continued over the course of 6 weeks, while the release of simvastatin from the core was delayed before being released over 4 weeks. Next, an infected, critically-sized rat femoral defect model was used to test different treatment methods with and without the composite bone graft substitute. Animals treated with locally released antibiotics had survivorship rates 24% higher than those treated with systemic antibiotics, and animals that received both antibiotics and an osteogenic drug had an increased amount of bone formation at 12 weeks compared to controls. Finally, several different anti-biofilm agents were evaluated for their ability to inhibit and/or disrupt the growth of Staphylococcus aureus (S. aureus) biofilms in vitro. Lysostaphin was the only drug investigated that was able to both inhibit and disrupt S. aureus biofilms. Furthermore, lysostaphin encapsulated into PLGAms maintained its bioactivity and may be useful for future incorporation into biofilm-combating materials. The bone grafting material developed here can be used to locally deliver drugs in a temporally controlled manner to reduce the number of procedures necessary for the treatment of complex IBDs.

This study develops a dynamic pricing model with a quality substitutable product, taking into account strategic and myopic consumers. In each of the two periods, the firm can choose between offering a high quality product, a low quality product or both and the corresponding price for the product. Strategic consumers compare current utility with future utility in order to decide the time of purchase and the quality of the product in an attempt to maximize their utilities. Myopic consumers consider only current utility in purchasing of the products. We generate scenarios, prove whether a scenario is feasible and which scenario produces the best profit for the firm. Our result suggests that the firm obtains the best profit when it provides only high quality products in each of the two periods. In other words, the firm does not have to offer quality substitution as intertemporal substitution suffices to maximize the expected profit.

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Two experiments were conducted to examine the effects of type of milk (whole; nonfat; nonfat, 70% lactose-reduced) and type of egg (fresh, whole egg; egg substitute) on the quality of baked custards. The egg substitute was a combination of dried egg whit e solids, dried low-fat, low-cholesterol egg yolk solids, and xanthan gum. Custard formulations served as prototypes for use in studies conducted in the Department of Food Science and Technology, Virginia Tech. In those studies, the effects of processing parameters on the quality of the custards were examined. The goal of all the studies was to develop shelf-stable lactose-reduced custard mixes that have potential for use in the foodservice industry. In Experiment I, chemical, physical, and sensory characteristics of a dessert type baked custard, made with sucrose, were examined. In Experiment II, the same characteristics were examined for a cheese flavored, entree type custard made without sucrose. Results indicate that use of nonfat and nonfat, 70% lactose-reduced milk in place of whole milk decreased significantly total fat and cholesterol concentrations in both types of custard mixes. Lactose-reduced milk also decreased lactose and increased galactose concentrations. The egg substitute decreased total fat and cholesterol concentrations and increased protein concentration. In general, lactose reduction had little effect on the physical and sensory characteristics of both types of custards, but the egg substitute affected these characteristics. Custards made with the egg substitute had less intense yellow color and greater gel strength than those made with fresh, whole egg. These custards also were less bright and more uneven in color and had weaker egg flavor and aftertaste. Based on results of this study, development of a lactose-reduced custard is feasible. However, additional studies are needed to examine potential for use of the formulations in the foodservice industry. Because the mixes could be used as bases for other types of products, such as custard pies, filled pastries, and quiches, studies that focus on development of those products could help define the niche for the mixes in the foodservice industry. Because of the trend in today1s market for reduced-fat, reduced-cholesterol foods, additional studies could be done to examine the effects of various types of egg substitutes on the quality of the custards. / Master of Science

Utilization of a fat substitute (100% replacement) with and without added fungal protease, fungal amylase, and bacterial amylase in a muffin was compared to a full fat counterpart. The enzymes were evaluated independently and in combination with each other. Physical and sensory data were reported with a p<0.05 significance level. The physical tests indicated that there were no significant differences (p>0.05) among any of the variations in volume, water activity (freshly baked, and after 24 and 48 hours storage), crumb L values and crust Land b values. The full fat muffin (control) was significantly (p<0.05) more tender than all formulations. In addition, the control had a significantly (p<0.05) lower moisture content and a significantly (p<0.05) more yellow crumb color than all the other variations. The 100% fat substituted muffins with enzymes, generally, had lower moisture contents, lower volumes, decreased staling rates, and an increased crumb tenderness when compared to the 100% fat substituted muffin without any enzymes. The 100% fat substituted muffins containing bacterial amylase or fungal protease alone had a significantly (p<0.05) lower staling rate than a 100% fat substituted muffin with a combination of bacterial amylase and fungal protease. / Master of Science

The purpose of this qualitative research paper was to explore how companies who offer plant-based meat and dairy substitutes in the Swedish market, can influence flexitarians towards a more plant-based diet. This was based on the conflict between the need to substitute animal products with more plant-based alternatives and the current resistance among consumers to change from traditional eating patterns. A qualitative research approach was adopted, where seven semi-structured interviews were conducted in the empirical data collection process. The sample included six leading brands in the Swedish market, namely Oatly, Oumph!, Sproud, Violife, Fry and ICA, and one industry expert named Mattias from Vegomagasinet. The research identified seven themes where two of them were most significant; the need to direct the communication to flexitarians and the importance of creating a taste and texture that is similar to meat and dairy. The five remaining influential factors concerned collaborations with stakeholders, challenging packaging design, transformative marketing, earned media and premium prices.

A rural, mid-sized district is experiencing great difficulty in the recruitment and retention of substitute teachers despite increased recruitment efforts. Such difficulty has resulted in numerous disruptions to the educational process. Despite their integral role in the educational process, research on substitute teachers remains absent from the literature. The purpose of this quantitative study was to assess the job satisfaction of substitute teachers with regard to differences between the two subgroups of certified and noncertified substitute teachers. This study was based on the two-factor theory. The research questions addressed the overall job satisfaction of substitute teachers, whether teacher job satisfaction (DV) differed by subgroup membership (IV), and the motivation and hygiene factors of substitute teaching. Survey data collection involved a cluster sampling of substitute teachers (N = 315, n = 51) working in four rural school districts experiencing shortages. Data were analyzed using ANOVA and thematic analysis. Demographic subgroups that reported above average job satisfaction were females, those with 1-3 years of experience, and those with the highest level of education being a bachelor's degree. The analysis uncovered a statistically significant difference between noncertified and certified substitute teachers only in the subcategory of satisfaction with pay, with certified substitute teachers being less satisfied. The most commonly reported motivation factors were the students, coworkers, and the nature of work; the most commonly reported hygiene factors were pay, student behavior, and communication. The study contributes to social change by identifying dissatisfying aspects of substitute teaching so that administrations may take action to alleviate the shortage, providing students with improved educational experiences with substitute teachers.