Doctor of Philosophy, The Ohio State University, 2019, Earth Sciences

Tide gauges record relative sea level (RSL), i.e. the vertical position of the sea surface relative to the adjacent land mass or relative to the seafloor under the gauge. A tide gauge cannot distinguish between a rise in sea level or subsidence of the land or seawall or pier that supports the gauge. Absolute sea level (ASL) refers to the level or height of the sea surface stated in some standard geodetic reference frame, e.g. ITRF2008. Since satellite altimeters make a geometrical measurement of sea level, this constitutes a determination of ASL. Satellite altimeters suffer from instrumental drift and thus need to be calibrated using tide gauges. This requires us to estimate the rate of RSL change at each tide gauge and convert this into an estimate of the rate of ASL change. This is done using a GPS station located at or near the tide gauge, since it can measure the vertical velocity of the lithosphere – often referred to as vertical land motion, VLM – which allows us to exploit the relationship ASL = RSL + VLM. This goal has motivated geodesists to build dozens of continuous GPS (or CGPS) stations near tide gauges – an agenda sometimes referred to as the CGPS@TG agenda. Unfortunately, a significant fraction of all long-lived tide gauges – especially those in the Pacific - have also recorded non-steady land motion caused by earthquakes. Rather than simply delete such datasets from the agenda, this thesis explores a new analytical method, based on the concept of a geodetic station trajectory model, that allows us to compute RSL and ASL rates even at tide gauges affected by regional earthquakes. We illustrate this method using two tide gauges (PAGO and UPOL) and three GPS stations (ASPA, SAMO and FALE) located in the Samoan islands of the Southwest Pacific. In addition to managing the impact of large regional earthquakes, we also seek new approaches to reducing noise in RSL rate estimates by suppressing the higher frequency sea level changes associated with ocean (open full item for complete abstract)

Committee: Michael Bevis (Committee Chair); C.K. Shum (Committee Member); Loren Babcock (Committee Member); Michael Barton (Committee Member) Subjects: Earth; Geological; Geophysical; Geophysics; Geotechnology; Ocean Engineering; Oceanography

Doctor of Philosophy, University of Toledo, 2017, Chemistry

Canavan disease is a progressive, fatal neurological disorder that is caused by defects in the human ASPA gene, which leads to an interruption in the metabolism of N-acetylaspartic acid (NAA). NAA is the second most abundant amino acid in the human brain. It is synthesized by aspartate N-acetyltransferase in neuronal mitochondria and is hydrolyzed by aspartoacylase in oligodendrocytes. Multiple therapies are currently under investigation to identify a treatment for Canavan disease. Aspartoacylase has previously been successfully expressed, kinetically characterized, and structurally characterized. To provide further insights about this enzyme, a series of mass spectrometry-based protein analysis studies have been performed. The amino acid sequence of aspartoacylase was confirmed by high-performance liquid chromatography/matrix-assisted laser desorption/ionization (MALDI) tandem mass spectrometry. No post-translational modifications, in particular asparagine-linked glycosylation that were previously implicated, were identified. Aspartate N-acetyltransferase (ANAT) has been shown to be a membrane associated enzyme with a putative membrane region of about 30 amino acid residues. While detergent extraction and several protein engineering approaches in the putative membrane domain failed to produce a soluble and active form of the enzyme, a tandem affinity purification approach using maltose-binding protein as fusion tag was able to produce an active and soluble enzyme form suitable for inhibitor development. Aspartate N-acetyltransferase was found to have high substrate specificity. Only three compounds, ß-methylaspartate, 2,3-diaminosuccinate, and L-glutamate, were identified as alternative substrates from 160 different amino acid analogs that were examined. Several factors that could affect ANAT activity were also tested. Triton X-100 and Tween 20 were identified to have the least impact on ANAT activity after a screening of a detergent library. The effect of v (open full item for complete abstract)

Committee: Ronald Viola (Committee Chair); Donald Ronning (Committee Member); Dragan Isailovic (Committee Member); Robert Blumenthal (Committee Member) Subjects: Analytical Chemistry; Biochemistry; Chemistry