Deuterium ratios (δD) of hydrated volcanic glass have been used to reconstruct paleoenvironments, although the reliability and proper sample preparation protocol have been debated. In this study, hydrated volcanic ash samples from the lee of the Cascades were prepared using two separate methods. Method 1 involves sonicating and rinsing samples with hydrochloric acid (HCl) followed by hand-selection of glass shards (125-212µm). Method 2 requires hydrochloric acid (HCl) and hydrofluoric acid (HF) abrasion as well as heavy liquid separation of shards (70-150µm). Method 2 produced more consistent results with decreased intra-replicate variability in both water content (-0.92 wt. %) and deuterium values (-2.5‰ δD). Method 2 δD values of ≥99% isotropic glass were also 2.5-10 % more negative relative to Method 1 values, with an increasing discrepancy with age (3.68-32.66 Ma). Method 2 results suggest volcanic glass did not re-equilibrate with modern water, based on 1) < 2‰ discrepancies between samples of the same ash flow taken from unique sample localities and 2) a ~20‰ difference between samples of different ages (~8 Ma apart) from the same locality. These results support the specified use of HF abrasion and heavy liquid separation on 70-150 µm glass shards to minimize the impact of contaminants on reconstructed paleowater δD values.

Quantum cascade laser (QCL) diodes have potential applications in many areas including emissions analysis and explosives detection, but like many solid-state devices they suer from degraded performance at higher temperatures. To alleviate this drawback, the thermal properties of the QCL diodes must be better understood. Using molecular dynamics (MD) and photothermal radiometry (PTR), the thermal conductivity of a representative QCL diode is computed and measured respectively. The MD results demonstrate that size eects are present in the simulated systems, but if these are accounted for by normalization to experimental results the thermal conductivity of the QCL can be reasonably obtained. The cross-plane conductivity is found to be in the range of 1.8 to 4.3 W=m K, while the in-plane results are in the range of 3.7 to 4.0 W=m K. These values compare well with experimental results from the literature for both QCL materials and for AlInAs and GaInAs, which the QCL is composed of. The cross-plane conductivity results are lower than those of either AlInAs or GaInAs, which demonstrates the phonon scattering at the interfaces. The in-plane results are between AlInAs and GaInAs, which is to be expected. The PTR results are less concrete, as there seem to be heat transfer eects active in the samples which are not included in the models used to t the frequency scans. These effects are not 2D heat transfer artifacts nor are they the result of volumetric absorption. It is possible that they are the results of plasmon induction, but this is only supposition. As the data stand, the PTR and MD results are within an order of magnitude of each other and follow reasonable trends, which suggests that both results are not too far o from reality. While the experimental results are not entirely conclusive, the simulations and experiments corroborate each other suciently to warrant further investigation using these techniques. Additionally, the simulations present sucient internal consistency so as to be useful for thermal property investigation independent of the PTR results.

A wavelet is a function which is used to construct a specific type of orthonormal basis. We are interested in using C*-algebras and Hilbert C*-modules to study wavelets. A Hilbert C*-module is a generalisation of a Hilbert space for which the inner product takes its values in a C*-algebra instead of the complex numbers. We study wavelets in an arbitrary Hilbert space and construct some Hilbert C*-modules over a group C*-algebra which will be used to study the properties of wavelets. We study wavelets by constructing Hilbert C*-modules over C*-algebras generated by groups of translations. We shall examine how this construction works in both the Fourier and non-Fourier domains. We also make use of Hilbert C*-modules over the space of essentially bounded functions on tori. We shall use the Hilbert C*-modules mentioned above to study wavelet and scaling filters, the fast wavelet transform, and the cascade algorithm. We shall furthermore use Hilbert C*-modules over matrix C*-algebras to study multiwavelets.

Tubulointerstitial fibrosis is the key histological predictor of the progression of declining renal function and the final common pathway of progressive kidney disease, regardless of aetiology. Despite its significance, there are currently no treatments available to abrogate this process and those that suffer with this burden eventually succumb to renal failure. Tubulointerstitial fibrosis is largely mediated by fibroblasts and myofibroblasts present in the interstitium. In response to injury, activated fibroblasts differentiate into myofibroblasts which serves as a histological hallmark of fibrosis. Myofibroblasts are characterised as the key contributors to interstitial volume and their presence ultimately leads to loss of renal function. The pathological entities leading to fibrosis inextricably depend on complex signalling pathways. Whilst many of the well-known growth factors that exert effects on renal fibroblasts (such as FGF, EGF and PDGF) involve the activation of receptor tyrosine kinases, the intracellular signalling events dictating the response of fibroblasts remain undefined. The kinase mTOR, responsible for integrating stress and amino acids and controlling cell growth, is increasingly recognised for its ability to integrate growth factor signals mediated through the upstream serine/threonine kinase PI3K. A number of recent studies have highlighted the role of PI3K and mTOR in the regulation of key events relevant to fibrosis, serving as a basis for Chapter 3: The role of PI3K and mTOR in the regulation of fibroblast proliferation and collagen synthesis, and the first part of Chapter 5: The role of PI3K and mTOR in the regulation of myofibroblast differentiation. These studies have identified a key role for PI3K and mTOR in the regulation of fibroblast proliferation, differentiation and collagen synthesis. The work described within has also attempted to examine the derivation of myofibroblasts via EMT. EMT is a process that is integral to embryogenesis and may act as an important source of myofibroblasts during fibrosis. This process is examined in Chapter 4: Development and validation of an ex vivo model of EMT. This model aims to better represent the in vivo environment and has also been used to identify novel regulators involved in EMT being utilised in the second part of Chapter 5: The role of PI3K and mTOR in EMT. Although cytokines and growth factors are thought to be chiefly responsible for tubulointerstitial fibrosis, we now know that serine proteases of the coagulation cascade may also play roles in renal disease. However, unlike their role in glomerular diseases, the role of coagulation in tubulointerstitial fibrosis is less well-known. The work described in Chapter 6: Constituents of the coagulation cascade are spatially and functionally related to experimental tubulointerstitial fibrosis has examined temporal and spatial in vivo relationships of coagulation factors and markers of fibrosis that aid our understanding of mechanisms of fibrosis. The aim of this thesis was to examine those facets of renal fibroblast function that are most devastating to renal function and culminate in an expansion of the renal interstitium during fibrosis. This work hopes to provide useful information to aid the understanding of the multifaceted mechanisms involved in renal tubulointerstitial fibrosis.

The Van Dyke's salamander (Plethodon vandyke,) is a rare species endemic to Washington State. It has been found in cool moist microhabitats along streams, splash zones of waterfalls, and headwater seeps. We explored the association of the Van Dyke's salamander with hydrologic condition, geomorphology, disturbance characteristics, and vegetation structure in first- and second-order streams, and headwater seeps in the Cascade Range of Washington. We conducted salamander surveys and measured habitat characteristics at 50 streams and 40 seeps May-October 2000-2002. We described Van Dyke's salamander occurrence in stream and seep sites at three spatial scales: between sites, within sites, and between microhabitat sites. Using presence and absence as the response, we fit logistic regression models predicting Van Dyke's salamander occurrence. To identify the model that best fit the data, we ranked a priori models using Bayesian Information Criterion (BIC). Results were consistent for both stream and seep sites, at all three spatial scales. Best approximating models indicated that Van Dyke's salamander occurrence at sites was related to geological and hydrological habitat characteristics that provided hydnc and thermal stability. The probability of Van Dyke's salamander occurrence along streams was associated with habitat characteristics that protected salamanders from exposure, provided a source cover, and stream habitat types providing splash zone areas. Between streams, Van Dyke's salamander occurrence was positively associated with the proportion of valley walls with canopy cover <5%, the proportion of the stream channel dominated by bedrock, boulder, or soil substrates, and additional stream channels entering the main channel. Within streams, the probability of Van Dyke's salamander occurrence increased with the presence of non-forested areas, the presence of bedrock dominated stream habitat types, and the presence of vertical or V-shaped valley wall morphology. Between microhabitat sites, the probability of Van Dyke's salamander occurrence increased with an absence of trees, the presence of seeps, and the presence of small cobble sized substrates. The probability of Van Dyke's salamander occurrence in seeps was associated with habitat characteristics that protected salamanders within the larger landscape, provided a moisture gradient from dry to saturated, and the presence of cover objects. Between seeps, Van Dyke's salamander occurrence was positively associated with seep faces having a dry and sheeting hydrology, and with seep faces >5 m high. Within seeps, the probability of Van Dyke's salamander occurrence was negatively associated with seeps that had proportionately more point measures of total overhead cover that were >25%. Between microhabitat sites, the probability of Van Dyke's salamander occurrence was positively associated with an increase in the percent cover of small cobble, small gravel, and bedrock substrates. We conducted mark-recapture surveys of the Van Dyke's salamander at two high-gradient stream sites located within the Cascade Range of Washington State, June-November 2002. Sites known to support populations of the Van Dyke's salamander were chosen, and were ecologically different. One site, lacking significant overstory and located within the blast zone created by the 1980 eruption of Mount St. Helens, was surveyed 10 times. The other site, located in an old-growth coniferous stand, was surveyed 11 times. Abundance of salamanders at the blast zone site was estimated to be 458 (95% Cl: 306-739). Abundance of salamanders at the old-growth site was estimated to be 100 individuals (95% Cl: 61-209). Capture probabilities were extremely low (5 = <0.10) for all trapping occasions at both sites, with an average capture probability for the two sites of 0.038 (range = 0.02-0.09). Analysis of movement patterns suggested that most individual salamanders had home ranges <2 m, at least when moving on or near the surface. Individuals were recaptured under the same cover object as initial capture 36% of the time, and 89% of the recaptured individuals moved <2 m. Our results indicated that populations of the Van Dyke's salamander were rare on the landscape, even within the species documented range. Van Dyke's salamander occurrence was associated with geological and hydrological habitat characteristics that created microhabitats favorable for a species that is especially sensitive to heat and drying due to physiological constraints. Animals were difficult to detect due to fossorial habits and low capture probabilities, and it is likely that the Van Dyke's salamander was not detected even at sites where it existed. Life history characteristics, such as lunglessness and fossorial habits, low capture probabilities, and low abundances make it difficult to manage for and protect the Van Dyke's salamander. However, habitat associations may be used to identify and protect habitats suitable for Van Dyke's salamander occurrence. / Graduation date: 2004

The greater Everglades ecosystem, including Florida Bay, has undergone significant anthropogenic manipulation over the past century. These actions resulted in a series of ecologically undesirable events in the Everglades ecosystem, prompting passage of the Comprehensive Everglades Restoration Plan (CERP). It is necessary to understand the variability in, and relationship between, salinity and ecology to fully evaluate the potential effects of CERP on Florida Bay. A seven-year dataset on surface salinity along with eleven-year and eight-year datasets on mesozooplankton and planktivorous fish were analyzed. Overall, mean Bay-wide salinity varied from a low of 24.2 just after the passing of Hurricane Irene in October 1999 to a high of 41.8 near the end of a drought period in July 2001. Bay-wide mean salinity exhibited dramatic decreases, up to 0.5 per day, whereas increases in bay-wide salinity were slower, with a maximum rate of 0.1 per day. Meteorological phenomena, such as tropical cyclones and ENSO, dramatically altered the salinity patterns of Florida Bay on interannual time scales. There was a large degree of spatial heterogeneity in salinity between sub-regions of Florida Bay due to differing freshwater sources and geomorphology. Mesozooplankton abundance displayed interannual variability and a positive correlation with salinity. Both of these features were also closely correlated with abundance of the dominant planktivorous fish, Anchoa mitchilli, indicating the importance of top-down control. The hypersaline periods appear to provide a refuge from predators, allowing mesozooplankton to increase in abundance during periods of increased physiological stress. The interaction between mesozooplankton and A. mitchilli, along with its correlation to salinity, was further investigated through the development of a mechanistic model of the populations in Florida Bay. The model indicated predation alone was insufficient to control mesozooplankton populations; rather, it was necessary to incorporate density-dependence utilizing a logistic prey population. With both mechanisms the model was able to replicate the observed interannual variability pattern and positive correlation between mesozooplankton and salinity. A preliminary management scenario evaluation suggests a two to six-fold difference in A. mitchilli and mesozooplankton populations between targeted and general salinity reductions. This suggests alternative freshwater management scenarios could produce drastically different ecological consequences.

Hydroamination stands as a desirable approach to nitrogen-containing molecules, which have important applications ranging from pharmaceuticals (fine chemicals) to paints, coatings, insecticides and agrochemicals (bulk chemicals). It features the use of alkene and alkyne starting materials, which are abundant and rarely used in the formation of C-N bonds. This work aims at building on the improved Cope-type reactivity developed in the Beauchemin group by expanding the reach of the reaction and understanding its mechanistic complexities. The first part of this thesis describes the development of cascade reactions to provide a thermodynamic driving force for the intermolecular Cope-type hydroamination of alkenes. The methodology serves as a proof of concept that the dipolar reaction intermediates can be engineered to further react irreversibly to more stable products, and has shown potential in improving the syntheses of natural alkaloids. The second part of the thesis describes the expansion of Cope-type hydrazide hydroaminations through a systematic investigation of hydrazine analogs as reactants. Optimized reagents are featured in the first reported intermolecular Cope-type hydrohydrazidation of alkenes. Mechanistic investigations and isolation of ammonium ylide intermediates support a 5-membered concerted and planar mechanistic pathway for hydrazide hydroaminations, similar to that observed with hydroxylamines. The final section presents mechanistic data disproving a previously assumed difficult proton transfer step in the hydroamination using hydroxylamines. From such findings, early results are presented towards a hydrogen-bond catalyzed hydroamination, which has potential applicability across the field of Cope-type hydroaminations and beyond.

In recent years, N-hetereocyclic carbenes (NHCs) have received considerable attention as organocatalysts due to their unusual ability to induce a reversal of reactivity (Umpolung) in aldehydes. Indeed, NHCs unique properties have been applied to the efficient and metal-free synthesis of organic compounds that have proven elusive using traditional approaches.<p> My Masters research program has been focused on the use of NHCs as organocatalysts in ring expansion reactions and their applications to cascade reactions.<p> During my Masters studies, an NHC-catalyzed efficient ring expansion of 4-, 5-, and 6-membered oxacycloalkane-2-carboxaldehydes to generate the corresponding lactone derivatives was developed. This reaction provides access to a variety of lactones using readily available NHCs under mild conditions.<p> Then, the ring-expansion lactonization has been successfully extended to an efficient lactamization using azacycloalkane-carboxaldehydes, which could provide functionalized lactams in moderate yields under mild conditions.<p> In addition, intrigued by the possibility of effecting the Umpolung of electron-poor dienes using NHC catalysts, the ring-expansion lactonization was applied to an attempted Diels-Alder-ring expansion cascade reaction. Though no cascade reactions were observed, some very interesting results were obtained, and those results will guide future investigations in this area.

The synthesis of fused nitrogen heterocycles has been investigated. Chapter 1 describes the synthesis of quinolones through a copper catalyzed amide coupling to ortho acetyl aryl halide followed by an aldol condensation that produces the quinolone in modest to good yields. The reaction works well with lactam partners and leads to tricyclic ring systems. Chapter 2 describes the synthesis of 8 membered enamide rings through a [3,3] sigmatropic rearrangement ring expansion of N-vinyl β-lactams. The N-vinyl β-lactams also undergo a 6π electrocyclization following the [3,3] sigmatropic rearrangement to furnish amino cyclobutanes. Previously reported amino cyclobutanes have been made using [2+2] photocycloaddition and resulted in a mixtures of diastereoisomers. Our method produces the amino cyclobutanes in good to high yields and with excellent levels of diastereoselectivity. Chapter 3 describes the synthesis and applications of reduced hydantoins from aziridine aldehydes and isocyanates. The resulting heterocycles contain an aziridine ring fused to a 5 membered urea. We also demonstrate that the reduced portion of the hydantoin, namely the hydroxyl group, can undergo further displacement with β-ketoesters similar to iminium ion chemistry.

Graduation date: 1991