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This thesis reports an investigation and discovery of an inhibitor of O-acetylpeptidoglycan esterase 1a (Ape1a). With the rise in rates of antibiotic resistant microbes it is becoming increasingly important to discover new targets related to the cell wall, cell membrane, or synthesis of nucleic acids and proteins. Ape1a, an esterase responsible for cleaving the acetyl group from MurNAc and allowing the activity of muramidases, presented as a potential target. Optimal storage conditions of the enzyme were determined and an assay that was amenable to high throughput screening (HTS) was developed. Ape1a was then screened against a selection from the Canadian Compound Collection in an effort to discover an inhibitor. Several compounds were determined to be false positives; however one compound, purpurin, showed true inhibition. MICs performed 'in vivo' on various Gram positive and Gram negative organisms corroborated the microtitre plate findings. These findings were further supported by results from testing performed on PO, Ape1a's natural substrate. Purpurin was found to be an effective inhibitor of 'B. cereus', an O-acetylated organism, at a relatively low concentration of 16 [mu]g/ml. These results supported the hypothesis that Ape1a is necessary for cell viability in organisms possessing Ape1a Thus, this compound serves as a potential target for drug development and may aid in the fight against drug resistant microbes.

This document was created to identify and clarify points of interest and concern that are of significance to community members of Zebulon, North Carolina. The document is divided into two main sections. The first is a compilation of secondary data collected for Zebulon, and when possible, for Wake County and the State of North Carolina to use as comparisons. The second section addresses various topics brought to light during interviews with both community members and service providers within the Town. In essence, this document examines the congruence and differences between secondary data and the community���s perceptions concerning various topics of interest. Over the course of the interviewing process, many members of the Zebulon community shared their thoughts, beliefs, and experiences to help illuminate the most salient issues. The subsequent characteristics were identified as some of the most important, and hence, contributed greatly to the completion of this document: Community Characteristics: The small town of Zebulon is known as ���The Town of Friendly People��� and does a great deal to live up to its name. Many of the Town residents have lived there for a long period of time. Consequently, many residents enjoy familiarity with one another, close family ties, and a sense of history and community in the area. There is widespread community support within the Town from both individuals and community organizations such as churches, civic groups, and service agencies. Although Zebulon is a rural town, it now faces some issues more typical of urban centers. These issues are rapid and expansive growth, ethnic and language diversity within the population, public housing, increased crime and drugs, and growing industry and commercialization. The rapid change and growth that Zebulon has experienced in the last several years brings with it many needs and challenges, many demanding the attention of the Town and County governments. There is significant interest among residents and Town officials in handling the change and growth in Zebulon, especially concerning meeting the needs of the community through the provision, improvement, and assurance of services. Directions and Challenges: Zebulon is in the midst of a period of growth and change that the Town never before experienced. The recent annexation of Wakefield is an example of the community���s expansion, and one that illustrates some of the concerns facing Town Hall. The addition of more people means an increase in need for existing services and perhaps the development of new services. While growth is a welcomed sight for some members of Zebulon, many see it as a movement away from the traditionally held values and familiarity that come from living in a small town. The adjustment period has already started for some individuals in the community, but many steps have yet to be taken to make the Town accessible to everyone who calls it home. Several of the churches and civic organizations have offered their services to help new members to the community feel welcome, namely the growing Hispanic population. In addition, the new police chief has made a commitment to actively involving the police department in the community, thus showing one example of how the Town and its residents can work together to make Zebulon a better place for everyone. As continued growth and change face the Town, community members and service providers are preparing to address the challenges these bring. Many of the people interviewed have strong feelings and opinions about their Town and the direction in which it is moving. The greatest endeavor for Zebulon may focus on communication among Town officials, services providers, and community members to ensure a future that benefits all living and working within Zebulon.

Background: Prior studies have demonstrated an association of depression with adverse clinical outcomes in patients with HFrEF, but the possible mechanisms responsible for the association are not unserstood., Methods: 142 men and women with HFrEF were enrolled through HF clinics and followed over time. At baseline and 6-months, depression was assessed by the Beck Depression Inventory (BDI-II) and disease activity by B-type natriuretic peptide (BNP). Proportional Hazards Regression Models assessed the contribution of depressive symptoms and HFrEF disease biomarkers on death or cardiovascular hospitalization., Results: Over a median follow-up period of 4 years, 42 patients (30%) died, and 84 (60%) had cardiovascular hospitalizations. A 10-point higher baseline BDI-II score was associated with a 35% higher hazard of death or cardiovascular hospitalization. Greater baseline BDI-II scores were associated with poorer HF self-care maintenance (R=-0.30, p<0.001) and fewer daily steps (R=-0.19, p=0.04), suggesting that depression may adversely affect important health behaviors. Increases in plasma BNP over 6 months were associated with worse outcomes. Changes in BDI-II score and plasma BNP over 6 months were positively correlated (R=0.25, p=0.004)., Conclusions: This study underscores the importance of elevated depression symptoms and their association with an increased likelihood of adverse clinical outcomes in patients with HFrEF. Health behaviors may play a greater role than direct biobehavioral pathways in the adverse effects of depression on the HF disease trajectory and resultant clinical outcomes.