Invisible Things: An Inquiry into the Laws of Nature

What are the laws of nature? Are they abstract entities that govern physical processes? Or are they merely useful summaries that describe patterns in nature? In this thesis, I explore offer arguments for the former view– what is known as inflationism regarding laws of nature. It is my hope that by excavating and evaluating the role epistemological concerns have played in this debate, we may find new avenues to break this long-standing metaphysical stalemat

Using the Comparative Toxicogenomics Database to Understand the Impact of High-Risk Toxicants on Biological Pathways

The role of environmental contaminant exposure in the development of a broad suite of human diseases has been well established. An understanding of the biological mechanisms through which these diverse and prevalent toxicants cause toxicity would be beneficial to both public health and clinical medicine. Here, we used a systematic analysis of data available from the Comparative Toxicogenomics Database to explore known toxicant-gene-disease interactions for 83 high-priority toxicants, as ranked by the Agency for Toxic Substances and Disease Research. Rankings of toxicant-pathway associations identified specific biological pathways enriched for disruption by numerous toxicants such as the Mitogen-Activated Protein Kinase (MAPK) pathway. These results present a novel approach to identify and prioritize biological pathways of particular relevance to high-priority environmental contaminants.Master of Science in Public Healt

Direct evidence for cholesterol crystalline domains in biological membranes: role in human pathobiology

AbstractThis review will discuss the use of small-angle X-ray diffraction approaches to study the organization of lipids in plasma membranes derived from two distinct mammalian cell types: arterial smooth muscle cells and ocular lens fiber cells. These studies indicate that cholesterol at an elevated concentration can self-associate and form immiscible domains in the plasma membrane, a phenomenon that contributes to both physiologic and pathologic cellular processes, depending on tissue source. In plasma membrane samples isolated from atherosclerotic smooth muscle cells, the formation of sterol-rich domains is associated with loss of normal cell function, including ion transport activity and control of cell replication. Analysis of meridional diffraction patterns from intact and reconstituted plasma membrane samples indicates the presence of an immiscible cholesterol domain with a unit cell periodicity of 34 Å, consistent with a cholesterol monohydrate tail-to-tail bilayer, under disease conditions. These cholesterol domains were observed in smooth muscle cells enriched with cholesterol in vitro as well as from cells obtained ex vivo from an animal model of atherosclerosis. By contrast, well-defined cholesterol domains appear to be essential to the normal physiology of fiber cell plasma membranes of the human ocular lens. The organization of cholesterol into separate domains underlies the role of lens fiber cell plasma membranes in maintaining lens transparency. These domains may also interfere with cataractogenic aggregation of soluble lens proteins at the membrane surface. Taken together, these analyses provide examples of both physiologic and pathologic roles that sterol-rich domains may have in mammalian plasma membranes. These findings support a model of the membrane in which cholesterol aggregates into structurally distinct regions that regulate the function of the cell membrane

eNOS transfection of adipose-derived stem cells yields bioactive nitric oxide production and improved results in vascular tissue engineering.

This study evaluates the durability of a novel tissue engineered blood vessel (TEBV) created by seeding a natural vascular tissue scaffold (decellularized human saphenous vein allograft) with autologous adipose-derived stem cells (ASC) differentiated into endothelial-like cells. Previous work with this model revealed the graft to be thrombogenic, likely due to inadequate endothelial differentiation as evidenced by minimal production of nitric oxide (NO). To evaluate the importance of NO expression by the seeded cells, we created TEBV using autologous ASC transfected with the endothelial nitric oxide synthase (eNOS) gene to produce NO. We found that transfected ASC produced NO at levels similar to endothelial cell (EC) controls in vitro which was capable of causing vasorelaxation of aortic specimens ex vivo. TEBV (n = 5) created with NO-producing ASC and implanted as interposition grafts within the aorta of rabbits remained patent for two months and demonstrated a non-thrombogenic surface compared to unseeded controls (n = 5). Despite the xenograft nature of the scaffold, the TEBV structure remained well preserved in seeded grafts. In sum, this study demonstrates that upregulation of NO expression within adult stem cells differentiated towards an endothelial-like lineage imparts a non-thrombogenic phenotype and highlights the importance of NO production by cells to be used as endothelial cell substitutes in vascular tissue engineering applications

Sphingosine-1-phosphate promotes the differentiation of adipose-derived stem cells into endothelial nitric oxide synthase (eNOS) expressing endothelial-like cells.

BACKGROUND: Adipose tissue provides a readily available source of autologous stem cells. Adipose-derived stem cells (ASCs) have been proposed as a source for endothelial cell substitutes for lining the luminal surface of tissue engineered bypass grafts. Endothelial nitric oxide synthase (eNOS) is a key protein in endothelial cell function. Currently, endothelial differentiation from ASCs is limited by poor eNOS expression. The goal of this study was to investigate the role of three molecules, sphingosine-1-phosphate (S1P), bradykinin, and prostaglandin-E1 (PGE1) in ASC endothelial differentiation. Endothelial differentiation markers (CD31, vWF and eNOS) were used to evaluate the level of ASCs differentiation capability. RESULTS: ASCs demonstrated differentiation capability toward to adipose, osteocyte and endothelial like cell phenotypes. Bradykinin, S1P and PGE were used to promote differentiation of ASCs to an endothelial phenotype. Real-time PCR showed that all three molecules induced significantly greater expression of endothelial differentiation markers CD31, vWF and eNOS than untreated cells. Among the three molecules, S1P showed the highest up-regulation on endothelial differentiation markers. Immunostaining confirmed presence of more eNOS in cells treated with S1P than the other groups. Cell growth measurements by MTT assay, cell counting and EdU DNA incorporation suggest that S1P promotes cell growth during ASCs endothelial differentiation. The S1P1 receptor was expressed in ASC-differentiated endothelial cells and S1P induced up-regulation of PI3K. CONCLUSIONS: S1P up-regulates endothelial cell markers including eNOS in ASCs differentiated to endothelial like cells. This up-regulation appears to be mediated by the up-regulation of PI3K via S1P1 receptor. ASCs treated with S1P offer promising use as endothelial cell substitutes for tissue engineered vascular grafts and vascular networks

Algorithm Development and Computer Graphic Simulation of an Articulated Transporter/ Manipulator System

The University of Florida is part of a multi-university research effort, sponsored by the U.S. Department of Energy, which is underway to develop and deploy an advanced semi-autonomous robotic system for use in nuclear power stations. The robotic system being designed by the Florida/Odetics team can be described . as an Articulated Transporter/Manipulator System (ATMS) which has several unique motion and transport capabilities. The ATMS will be capable of performing tasks in radioactive hazardous environments to reduce occupational radiation exposure of plant personnel and to increase the availability of the plant. This paper will describe the key design and control features of the ATMS with emphasis placed on the implementation of specific motion control algorithms

A remote telepresence robotic system for inspection and maintenance of a nuclear power plant

Progress in reported in the areas of environmental hardening; database/world modeling; man-machine interface; development of the Advanced Liquid Metal Reactor (ALMR) maintenance inspection robot design; and Articulated Transporter/Manipulator System (ATMS) development

Understanding and valuing the broader health system benefits of Uganda’s national Human Resources for Health Information System investment

Background\ud To address the need for timely and comprehensive human resources for health (HRH) information, governments and organizations have been actively investing in electronic health information interventions, including in low-resource settings. The economics of human resources information systems (HRISs) in low-resource settings are not well understood, however, and warrant investigation and validation.\ud \ud Case description\ud This case study describes Uganda’s Human Resources for Health Information System (HRHIS), implemented with support from the US Agency for International Development, and documents perceptions of its impact on the health labour market against the backdrop of the costs of implementation. Through interviews with end users and implementers in six different settings, we document pre-implementation data challenges and consider how the HRHIS has been perceived to affect human resources decision-making and the healthcare employment environment.\ud \ud Discussion and evaluation\ud This multisite case study documented a range of perceived benefits of Uganda’s HRHIS through interviews with end users that sought to capture the baseline (or pre-implementation) state of affairs, the perceived impact of the HRHIS and the monetary value associated with each benefit. In general, the system appears to be strengthening both demand for health workers (through improved awareness of staffing patterns) and supply (by improving licensing, recruitment and competency of the health workforce). This heightened ability to identify high-value employees makes the health sector more competitive for high-quality workers, and this elevation of the health workforce also has broader implications for health system performance and population health.\ud \ud Conclusions\ud Overall, it is clear that HRHIS end users in Uganda perceived the system to have significantly improved day-to-day operations as well as longer term institutional mandates. A more efficient and responsive approach to HRH allows the health sector to recruit the best candidates, train employees in needed skills and deploy trained personnel to facilities where there is real demand. This cascade of benefits can extend the impact and rewards of working in the health sector, which elevates the health system as a whole

A remote telepresence robotic system for inspection and maintenance of a nuclear power plant

This annual report details the activities of the University of Florida research on the robotic system for inspection and maintenance of nuclear power plants. (FI