published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

Salamanders have a remarkable ability to regenerate complex body parts including the limb, tail, and central nervous system. Although salamander regeneration has been studied for several hundred years, molecular-level studies have been limited to a relatively few important transcription factors and signaling molecules that are highly conserved among animals. Physiological genomic approaches were used here to investigate spinal cord and limb regeneration. Chapter 2 reports that hundreds of gene expression changes were identified during spinal cord regeneration, showing that a diverse injury response is activated in concert with extracellular matrix remodeling mechanisms during the early acute phase of natural spinal cord regeneration. Chapter 3 presents results that identify the salamander ortholog of mammalian Nogo-A, a gene known to inhibit mammalian nerve axon regeneration. Nogo-A gene expression was characterized during salamander development and adulthood in order to address the roles of Nogo-A in the nervous system. Chapters 4 and 5 use physiological genomic approaches to examine limb regeneration and why this process is dependent upon an intact nerve supply. Results presented in Chapter 4 showed that many processes regulated during early limb regeneration do not depend upon nerve-derived factors, but striking differences arise between innervated and denervated limbs by 14 days after amputation. Chapter 5 identified genes associated with peripheral nerve axon regeneration and identified gene candidates that may be secreted by nerves to support limb regeneration. Lastly, chapter 6 characterizes the expression of a developmentally important family of genes, matrix metalloproteinases, during tail regeneration. These results suggest that matrix metalloproteinases play multiple roles throughout the regeneration process. Primarily, this dissertation presents data from the first genomic studies of salamander regeneration. The results suggest genes such as matrix metalloproteinases, and molecular pathways such as the Wnt and FGF signaling pathways that can be exploited to enhance regenerative ability in humans.

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Fenton-dependent recovery of carbon initially saturated with one of several chlorinated aliphatic contaminants was studied in batch and continuous-flow reactors. A specialty carbon, URV-MOD 1 (Calgon) was employed to minimize non-productive H2O2 demand - that which does not yield hydroxyl or superoxide radicals.Enhancement of PCE degradation kinetics by ferric iron addition is limited by iron solubility, even at relatively low pH. Quinone addition increased the pseudo-first-order rate constant for PCE loss temporarily. Only copper addition sustainably enhanced the specific rate of PCE loss. For copper-to-iron molar ratios of 0.25 to 5, the pseudo-first-order rate constant for PCE transformation was increased by a factor of 3.5. It is apparent that the effect of copper addition on Fenton-dependent reaction rates is complex, and involves a shift in chemical mechanism, as indicated by the differing slopes in the Arrhenius plot (with and without copper).A mathematical model was developed to evaluate the effect of operational parameters ([Fe(III)]T:[H2O2]o ratio and pH) on degradation kinetics and optimize the PCE degradation process in homogeneous reaction mixtures. The model simulated experimental degradation of the organic target in a homogeneous Fenton-reaction system. The model requires further refinement to simulate Fenton's systems in which ions in solution (such as sulfate and chloride) play significant roles.In continuous-flow reactors, Fenton's reagents were cycled through spent GAC in columns to degrade one of seven chlorinated compounds tested. The contaminant with the weakest adsorption characteristics, methylene chloride, was 99% lost from the carbon surface during a 14-hour regeneration period. At the field site, the GAC was saturated with gases containing TCE and PCE from a soil vapor extraction (SVE) system. In the field, up to 95% of the sorbed TCE was removed from GAC during regeneration periods of 50-60 hours. Recovery of PCE-loaded GAC was significantly slower. Column experiments show that there is minimal loss of carbon adsorption capacity during Fenton treatment and that the rate of GAC regeneration is compound specific. Scoping-level cost estimates indicated that field use of Fenton regeneration is not cost effective without optimization and/or iron surface amendments, except in the case of the most soluble VOCs.

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