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The central Garlock fault in California offers a unique opportunity to collect a large volume of useful data to determine its incremental slip rate during the Holocene. The slip rate of the central Garlock fault through the Holocene is based on slip-rate studies and the timing of events interpreted from paleoseismic studies. Understanding the ages of displaced sediments in offset geomorphic features will develop a better understanding of the slip rate. Optically stimulated luminescence (OSL) can be used to date the burial age of these displaced sediments. However, OSL dating has its challenges. Many models may either consider the possibility of incomplete bleaching or the mixing of different aged grains. At the luminescence laboratory at UCLA, the informal "discrete minimum method" (DMM) attempts to consider both of these challenges. In order to examine the reliability of the DMM, the luminescence data of samples collected along the central Garlock fault at the Christmas Canyon west site were analyzed. This analysis included the statistical assessment of each sample's sensitivity and probability of estimated equivalent dose values. Also, an evaluation of the same data was conducted using Galbraith's (2005) finite-mixture model as well as the minimum-age models by Galbraith et al. (1999). Probability distributions indicated at least two sensitivity groups within each sample. Because differences in sensitivity are probably derived from different types of source rock, multiple types of feldspar are likely contributing to each sample's luminescence signals. Polymodal, wide and skewed unimodal PDF's and KDE's of the equivalent doses indicate mixed dose populations within the majority of CCW samples. Finite-mixture modelling is an effective indicator of a sample having internal De variability. However, it does not indicate which component corresponds to the burial age of a sediment layer. Minimum-age modeling may be effective at determining the minimum age of a sample, but does not consider the possibility of a younger component being introduced into a sediment layer. This may result in an underestimation of De for some samples. The "Discrete Minimum Method" appears to address the existence of mixed dose populations at the CCW site while separating the groups of unbleached and any other mixed grains unreasonable to use for De estimation.

Insulin stimulates glucose uptake in muscle and fat by promoting translocation of the facilitative transporter GLUT4 from intracellular compartments to the plasma membrane. Members of the Ras superfamily of small G proteins regulate distinct steps in the GLUT4 trafficking itinerary. The G protein RalA promotes GLUT4 vesicle trafficking to the plasma membrane through its interactions with the actin motor Myo1c and a tethering complex called the exocyst. RalA is activated in response to insulin in 3T3-L 1 adipocytes, however little is known about the proteins regulating this small G protein. An siRNA-based screen for RalA regulators led to the identification of the RalGAP Complex in 3T3-L1 adipocytes. The RalGAP Complex is composed of the regulatory subunit RGC1 (previously identified as KIAA1l219) and the catalytic subunit RGC2 (previously identified as AS250). RGC2 contains a GAP domain at its C-terminus that promotes GTP hydrolysis on RalA and RalB. In 3T3-L1 adipocytes, RGC2 knockdown results in increased basal and insulin-stimulated activation of RalA, demonstrating that this protein negatively regulates RalA. RGC1 binds to RGC2 and is essential for stability of RGC2 protein and regulation for RalA by the Ral GAP Complex. Knockdown of RGC1 or RGC2 increases insulin-stimulated glucose uptake and surface GLUT4 levels, establishing a regulatory role of this complex in glucose transport. RGC2 is directly phosphorylated by Akt2 on at least three residues in response to insulin. Overexpression of active Akt blocks the effects of RGC1/2 on RalA activity, demonstrating that phosphorylation of RGC2 inhibits the complex. Akt2 likely does not affect the catalytic activity of RGC2, but instead results in 14-3-3 binding to and a conformational change in the complex that may occlude it from binding to RalA. The RalGAP GARNL1 serves as an alternative catalytic subunit in the RalGAP complex. This protein is expressed at low levels in adipocytes and does not affect RalA activity or glucose uptake in these cells. However, GARNL1 is expressed in muscle and may regulate RalA activity in response to cellular stimuli in these cells. Together, these data demonstrate that the RalGAP Complex functions as a negative regulator of RalA activity in diverse cellular contexts.

Multiple brain stem nuclei, including locus coeruleus (LC), dorsal raphe nucleus (DR), and the oral (PnO) and caudal (PnC) part of the pontine reticular formation participate in the modulation of arousal states. Hypothalamic neurons containing the arousal promoting peptides hypocretin-1 and hypocretin-2 project to each of these brain stem nuclei. Both peptides bind to two receptors with different high affinities. G protein activation and acetylcholine (ACh) release were used in this thesis research to elucidate the yet unknown mechanisms by which hypocretin in the brain stem exerts arousal state control. Hypocretin-1 activated G proteins in LC, DR, PnO, and PnC of rat as shown by in vitro [35S]GTPgammaS autoradiography. In all nuclei investigated, G protein activation by hypocretin-1 was concentration-dependent, saturable, and blocked by a hypocretin receptor antagonist. Microinjection of pertussis toxin (PTX) into rat PnO inhibited hypocretin-1-stimulated G protein activation, demonstrating that some hypocretin receptors in the PnO couple to PTX-sensitive G proteins. PnO microdialysis delivery of hypocretin-1 increased ACh release, suggesting that hypocretin regulates arousal states in part by modulating ACh release in PnO. PTX did not block hypocretin-l-stimulated ACh release in PnO, demonstrating that the hypocretin receptors modulating ACh release couple to PTX-insensitive G proteins. Hypocretin-1 and hypocretin-2 each caused a concentration-dependent increase in ACh release with similar EC50 values, indicating that hypocretin-2 receptors modulate ACh release in rat PnO. At higher concentrations, hypocretin-1 was more efficacious in stimulating ACh release than hypocretin-2, suggesting that hypocretin-1 receptors also modulate ACh release in the PnO. These results support the conclusion that both hypocretin receptor subtypes modulate ACh release in rat PnO. Results from this thesis support the functional interpretation that the hypocretin ligand-receptor system in the PnO contributes to the maintenance of behavioral state stability by modulating ACh release. This modulation may occur via hypocretin receptors coupled to PTX-insensitive G proteins that are proposed to be located on glutamatergic postsynaptic PnO neurons. Hypocretin receptors coupling to PTX-sensitive G proteins may be located presynaptically on terminals of hypocretin neurons and may function as autoreceptors that regulate hypocretin release in the PnO.

In electron cyclotron resonance heating (ECRH) wave sources heat a plasma linearly with respect to intensity, but as the intensity of ECRH gets larger, there might appear nonlinear effects that would result in cutoff of net absorption. This thesis uses quantum mechanical theory to derive a threshold microwave intensity for nonlinear absorption. The quantum mechanical theory estimates that the threshold microwave intensity for nonlinear absorption is about 10('5) watts/cm('2) for a microwave heating experiment (T(,e) = 100 ev, (lamda) = 3.783 cm, B = 2.5 kG). This value seems large considering the present power capabilities of microwave sources (10('2) (TURN) 10('3) watts/cm('2)), but for a low temperature plasma, this threshold will go down. There is another nonlinear phenomenon called stimulated cyclotron scattering which enhances photon scattering by electrons gyrating in a magnetic field. This is expected to prevent incoming photons from arriving at the central region of the fusion plasma, where absorption mainly takes place. Theory based on a photon transport model predicts that the threshold intensity for the stimulated cyclotron scattering is about 10('4) watts/cm('2) for the plasma parameters mentioned above. This value seems large also, but a longer wavelength of microwaves and a larger magnitude magnetic field, which will be the case in reactor type facilities, will lower the threshold intensity to levels comparable with the currently developed microwave sources.

This dissertation describes the effects of neuronal injury on glutamate receptor-coupled phosphoinositide (PPI) turnover in immature rats. Glutamate is the major excitatory neurotransmitter in the mammalian CNS. Overstimulation of glutamate receptors elicits excitotoxicity that may contribute to the neuronal injury resulting from cerebral ischemia. In the immature rat brain, the glutamate agonist quisqualate (QUIS) potently stimulates PPI hydrolysis. To study the mechanisms of ischemic brain injury and glutamate excitotoxicity, I characterized QUIS-stimulated PPI turnover in the in vivo animal models of perinatal brain injury: (1) ischemic-hypoxic brain injury and (2) N-methyl-D-aspartate (NMDA)-induced brain injury. In the first model, 7-day-old rats were exposed to 8% O$\sb2$ for 2 h after the right carotid artery was ligated. This insult produced neuronal injury in the ipsilateral hippocampus and striatum. In the second model, NMDA (17 nmole) was injected into the right striatum of 7-day-old rats. Iscehmia-hypoxia and NMDA produced brain lesions with similar pathology. QUIS-stimulated $\sp3$H-inositol phosphate release from hippocampal and striatal tissue slices in animals sacrificed 1 day after the ischemic-hypoxic insult or 3 days after NMDA injection was assayed. Both ischemia-hypoxia and NMDA-induced brain lesions doubled QUIS-stimulated PPI hydrolysis in the lesioned hippocampal and striatal slices. Carbachol, a cholinergic agonist which elicits PPI hydrolysis, did not preferentially stimulate lesioned tissue; this observation suggested that the enhanced PPI turnover was specific to the glutamate receptor. The EC$\sb{\rm 50s}$ of QUIS in stimulating $\sp3$H-IP$\sb1$ release were the same for both lesioned and unlesioned tissue. Extracellular Ca$\sp{2+}$ concentration influenced the extent of QUIS-stimulated PPI hydrolysis in lesioned tissue. Low extracellular Ca$\sp{2+}$ concentration (1 $\mu$M) further increased QUIS-stimulated PPI hydrolysis in NMDA-lesioned hippocampal and striatal slices by 50-60%, whereas carbachol-stimulated $\sp3$H-IP$\sb1$ release was unchanged. These results indicate that in two models of neuronal injury in perinatal rats the efficiency of glutamate receptor coupling to PPI hydrolysis increases acutely. However, the molecular mechanisms underlying this enhanced coupling are still unclear.

ATPase activity which is stimulated by submicromolar concentrations of Ca('2+) was identified and characterized in human placental microvillous brush border membranes. The enzyme exhibited an apparent K(,m) for free Ca('2+) of 18.3 (+OR-) 3.7 nM and a V(,max) of 233.0 (+OR-) 30.0 nmol/min/mg protein. Studies using trans-1,2-diaminocyclohexane-N,N,N',N',-tetraacetic acid (CDTA) showed this enzyme to require Mg('2+) for maximal activity. The high affinity Ca('2+)-ATPase was unaffected by up to 100 (mu)M concentrations of vanadate, but was sensitive to trifluoperazine inhibition (IC(,50) < 50 (mu)M). The enzyme was not stimulated by the addition of up to 10 (mu)g calmodulin, but this lack of effect may be related to the endogenous calmodulin content of the membrane preparation. High affinity Ca('2+)-ATPase was significantly inhibited by 1,1-Bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and its specific homologs at 10 (mu)M concentrations. In addition to the high affinity ATPase, an ATP-dependent Ca('2+) uptake was characterized in human placental microvillous brush border membranes. Multiple freeze-thaw cycles greatly diminished uptake activity by 90%, indicating an intravesicular accumulation of Ca('2+). Kinetic studies indicate an apparent K(,m) for calcium of 0.22 (+OR-) 0.04 M and a V(,max) of 441 (+OR-) 137 pmoles/min/mg protein at 37(DEGREES)C. Ca('2+) uptake was shown to have a optimum pH of 7.2, and was unaffected by the addition of oxalate, consistent with a plasma membrane origin of uptake. The activity was temperature dependent and was significantly inhibited by trifluoperazine (IC(,50) = 100 uM) and vanadate (IC(,50) = 100 uM). DDT and its specific homologs were shown to inhibit Ca('2+) uptake, but to a lesser degree than that seen with the high affinity Ca('2+)-ATPase. Thus, human term placental brush border membranes have both a Ca('2+) transport activity and a calcium-stimulated ATPase activity with similar biochemical characteristics. It is suggested that the high affinity Ca('2+)-ATPase is the mechanism responsible for Ca('2+) uptake in this membrane fraction, which functions to maintain the low intracellular level of free Ca('2+) in placental syncytiotrophoblasts.