Optical Precursor Behavior

Controlling and understanding the propagation of optical pulses through dispersive media forms the basis for optical communication, medical imaging, and other modern technological advances. Integral to this control and understanding is the ability to describe the transients which occur immediately after the onset of a signal. This thesis examines the transients of such a system when a unit step function is applied. The electromagnetic field is described by an integral resulting from Maxwell’s Equations. It was previously believed that optical precursors, a specific transient effect, existed only for only a few optical cycles and contributed only small magnitudes to the field. The main results of this thesis show that the transients arising from this integral are entirely precursors and that they may exist on longer time scales and contribute larger magnitudes to the field. The experimental detection of precursors has previously been recognized only through success comparison to the transient field resulting from an application of the method of steepest descent to that field integral. For any parameter regime where steepest descents may be applied, this work gives iterative methods to determine saddle points which are both more accurate than the accepted results and to extend into regimes where the current theory has failed. Furthermore, asymptotic formulae have been derived for regions where previous attempts at steepest descent have failed. Theory is also presented which evaluates the applicability of steepest descents in the represention of precursor behavior for any set of parameters. Lastly, the existence of other theoretical models for precursor behavior who may operate beyond the reach of steepest descent is validated through successful comparisons of the transient prediction of those methods to the steepest descent based results of this work.Dissertatio

<i>In vitro</i> screening of metal oxide nanoparticles for effects on neural function using cortical networks on microelectrode arrays

<p>Nanoparticles (NPs) may translocate to the brain following inhalation or oral exposures, yet higher throughput methods to screen NPs for potential neurotoxicity are lacking. The present study examined effects of 5 CeO₂ (5– 1288 nm), and 4 TiO₂ (6–142 nm) NPs and microparticles (MP) on network function in primary cultures of rat cortex on 12 well microelectrode array (MEA) plates. Particles were without cytotoxicity at concentrations ≤50 µg/ml. After recording 1 h of baseline activity prior to particle (3–50 µg/ml) exposure, changes in the total number of spikes (TS) and # of active electrodes (#AEs) were assessed 1, 24, and 48 h later. Following the 48 h recording, the response to a challenge with the GABA_A antagonist bicuculline (BIC; 25 µM) was assessed. In all, particles effects were subtle, but 69 nm CeO₂ and 25 nm TiO₂ NPs caused concentration-related decreases in TS following 1 h exposure. At 48 h, 5 and 69 nm CeO₂ and 25 and 31 nm TiO₂ decreased #AE, while the two MPs increased #AEs. Following BIC, only 31 nm TiO₂ produced concentration-related decreases in #AEs, while 1288 nm CeO₂ caused concentration-related increases in both TS and #AE. The results indicate that some metal oxide particles cause subtle concentration-related changes in spontaneous and/or GABA_A receptor-mediated neuronal activity <i>in vitro</i> at times when cytotoxicity is absent, and that MEAs can be used to screen and prioritize nanoparticles for neurotoxicity hazard.</p

Use of novel inhalation kinetic studies to refine physiologically-based pharmacokinetic models for ethanol in non-pregnant and pregnant rats

<div><p></p><p>Ethanol (EtOH) exposure induces a variety of concentration-dependent neurological and developmental effects in the rat. Physiologically-based pharmacokinetic (PBPK) models have been used to predict the inhalation exposure concentrations necessary to produce blood EtOH concentrations (BEC) in the range associated with these effects. Previous laboratory reports often lacked sufficient detail to adequately simulate reported exposure scenarios associated with BECs in this range, or lacked data on the time-course of EtOH in target tissues (e.g. brain, liver, eye, fetus). To address these data gaps, inhalation studies were performed at 5000, 10 000, and 21 000 ppm (6 h/d) in non-pregnant female Long-Evans (LE) rats and at 21 000 ppm (6.33 h/d) for 12 d of gestation in pregnant LE rats to evaluate our previously published PBPK models at toxicologically-relevant blood and tissue concentrations. Additionally, nose-only and whole-body plethysmography studies were conducted to refine model descriptions of respiration and uptake within the respiratory tract. The resulting time-course and plethysmography data from these <i>in vivo</i> studies were compared to simulations from our previously published models, after which the models were recalibrated to improve descriptions of tissue dosimetry by accounting for dose-dependencies in pharmacokinetic behavior. Simulations using the recalibrated models reproduced these data from non-pregnant, pregnant, and fetal rats to within a factor of 2 or better across datasets, resulting in a suite of model structures suitable for simulation of a broad range of EtOH exposure scenarios.</p></div