From 1939 to 1942 Canada, allied to the United Kingdom, prepared to defend itself against chemical attack by Nazi Germany. The Canadian preparations represented one of Canadas many contributions to the cause of the British Commonwealth, and may have been used as one method to counter British requests for additional ground troops. After the Japanese attack at Pearl Harbor, Canada became part of an alliance with the United States and the United Kingdom. Canadian chemical warfare preparations went from defensive to offensive following the attack on Pearl Harbor and the entry of the United States into the war. The chemical warfare preparations included preparation and testing of toxic gases and smokes, smoke screening and flame weapons.<p> One of the most important Canadian contributions to the alliance was the establishment of the Suffield Field Experimental Station in Alberta. This base was particularly useful in carrying out chemical weapon trials, during which approximately 2000 Canadian citizens and soldiers were exposed to toxic gases. At the beginning of the war chemical warfare volunteers were completely covered in protective clothing except for a patch to allow for controlled chemical burns. But by 1942 Suffield staff was given permission to rewrite the regulations for the trials, and volunteers often received significant chemical injuries, including to the eyes. It would appear that the full body of knowledge available to the wartime scientists, especially information relevant to the long-term health outcomes of exposure to vesicant agents, was not applied in the conduct of the human experimentation.

There are some 15,000 known organophosphorus chemicals. Some of these OP’s, including VX and paraoxon, demonstrate an acute neurotoxicity due to the inhibition of cholinergic enzymes. Organophosphorus chemical warfare agents and pesticide neurotoxins are subject to hydrolysis by OP degrading enzymes. To be useful as a bioremediation or anti-chemical warfare agent, the enzyme must be tailored for, and integrated into, a practical application platform. Several studies have established enzyme-based countermeasures, describing such diverse applications as decontaminating foams for surface remediation, encapsulating enzyme with liposome for in vivo therapy, enzyme attachments to surfaces for biosensors and development of a corn expression system for large-scale enzyme production. The goal of the research described here is to select, investigate and improve the operational potential of organophosphate-degrading enzymes including Organophosphorus Hydrolase (OPH, 3.1.8.1) and Organophosphorus Acid Anhydrolase (OPAA, 3.1.8.2). Using saturation kinetics, the catalytic efficiencies of these two major detoxification enzymes were characterized with substrates representing each class of OP neurotoxin, phosphotriester, phosphothioate and phosphofluoridate. OPH presents superior kinetic parameters with each OP class tested. Variants of OPH were created to increase the operational effectiveness of OP hydrolytic enzymes against phosphorothioates. An H254S/H257L mutation in the active site resulted in an improvement in the kinetics (kcat/KM) for the phosphorothioate, demeton-S. To screen potential vascular protection therapies, an in vitro protocol was developed to predict enzymatic effectiveness for protection of acetylcholinesterase from acute OP-inhibition. The protection abilities of the enzymes were directly related to their second order rate constants as inhibitory levels of OP are below the KM of the enzymes. Consideration of contaminant nature concentration and enzyme kinetic parameters, kcat and KM, is critical to understanding decontamination and effective use of enzyme technology. These technologies continue to develop and provide promising new decontamination tools for OP compounds.

Thesis (LL. M.)--McGill University, 2000. / Includes bibliographical references (p. 113-136). Also available via the Internet.

Thesis (M.S. in Defense Analysis)--Naval Postgraduate School, December 2009. / Thesis Advisor: Sepp, Kalev. Second Reader: Greenshields, Brian. "December 2009." Description based on title screen as viewed on February 1, 2010. Author(s) subject terms: Civil Affairs, Irregular Warfare, counterinsurgency, foreign internal defense, stability operations, special operations, future threat environment. Includes bibliographical references (p. 85-89). Also available in print.

Thesis (M.A.)--Naval Postgraduate School, 2002. / Thesis advisor(s): Gordon McCormick, Hy Rothstein. Includes bibliographical references (p. 81-85). Also available online.

Inaug.-diss.--Munich. / Lebenslauf. "Quellennachweis": p. 159-160.

Thesis (M.S. in Defense Analysis)--Naval Postgraduate School, June 2004. / Thesis advisor(s): Dorothy Denning. Includes bibliographical references (p. 125-130). Also available online.

Thesis (M.S. in Operations Research)--Naval Postgraduate School, June 2004. / Thesis advisor(s): Samuel E. Buttrey. Includes bibliographical references (p. 73-74). Also available online.

Thesis (D. Miss.)--Trinity International University, 2000. / Abstract. Includes bibliographical references (leaves 225-236).

Thesis--School of Advanced Airpower Studies, Maxwell Air Force Base, Ala., 1991-92. / Title from title screen (viewed Oct. 27, 2003). "May 1992." Includes bibliographical references.