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Gene delivery using an adenoviral system has been effective in introducing therapeutic proteins in vitro and in vivo. This study tested the feasibility of using adenovirus to deliver clinically relevant amounts of butyrylcholinesterase (BChE), a proven bioscavenger of nerve agents. The adenovirus construct expressed full-length mouse BChE. Mice were injected with a single dose of adenovirus (1.5 x 10(exp 10) infectious units) in the tail vein; plasma was collected through day 11 and assayed for BChE activity. Maximum activity, representing a 300- to 3400-fold increase over baseline, was found on day 4. Nondenaturing gel electrophoresis showed the recombinant BChE was a dimer that could be converted to tetramers by addition of polyproline. The toxic compounds chosen for protection studies were positively charged organophosphorus agents, echothiophate, and O-ethyl-S-2-N,N-diisopropylaminoethyl methylphosphonothiolate (VX). Mice containing elevated blood levels of BChE (300- to 3400-fold over the control mice) were challenged with incremental doses of echothiophate or VX. Mice showed no signs of toxicity and were protected from up to 30x LD50 dose of echothiophate and 5x LD50 does of VX. A good correlation was observed between tolerated echothiophate dose and plasma BChE levels at time of challenge. The absolute increases in levels of circulating BChE and the sustained nature of the response resulted in a very high enzyme concentration, deemed critical in acute toxicity (5x LD50 or more) scenarios. These results suggest that gene-delivered BChE is a prophylactic and affords protection equivalent to that of a multimilligram injection of the same., Published in The Journal of Pharmacology and Experimental Therapeutics, v337 n1 p92-101, 2011. Sponsored in part by DTRA. The original document contains color images.

This thesis presents a series of experimental studies based on using liquid crystals (LC) with planar optical lightwave components. Adaptive optical devices have been fabricated by combining LCs with direct UV written buried channel waveguide and Bragg grating structures. It has been discovered that the hysteresis seen in previous LC tunable Bragg grating devices is due to a process known as the pincement transition. Pincement involves the transition from a splay-bend wall in the nematic LC to a pair of oppositely charged half-integer disclination lines. The voltage-based transient behaviour of the pincement transition correlated with the tuning curve response seen in voltage controlled LC tunable gratings. In order to reduce the hysteresis effect a new grooved substrate geometry was introduced. Rather than accessing the Bragg grating vertically via a wet etch process, the substrates are precision machined using a dicing saw to allow side access. The result is significantly reduced hysteresis, with a maximum tuning range of over 1nm with the application of under 30V(pp). Tunable chirped Bragg gratings based on standard PCB technology using arrays of resistors as heating elements were designed and tested. The group delay slope of the chirped gratings was tuned by 4ps/nm using a combination of heating elements and thermoelectric cooling. Finally, LC compounds were then tested for suitability as waveguiding media. It was found that both hollow fiber and planar substrate systems using an LC as the core guiding medium successfully guided both visible and IR light at telecomms wavelengths

Compressive strengths of pumice-aggregate concrete were examined by introducing controlled variables into the mix proportions. A mix design method is presented, and this method was analyzed for consistency and feasibility.