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World events have conspired to increase the threat of the use of chemical and biological weapons. The end of the Cold War brought not only the hoped-for change of swords into plowshares but also political and economic turbulence in the former Soviet Union, unemployed and disenchanted weapons specialists and scientists, the rise of religious fundamentalism in southwest Asia, state- sponsored terrorism, and blurring of the lines between terrorism and tradi- tional warfare. In addition, the nature...
Topics: Nerve Agents, Vesicants, Riot Control Agents, Decontamination, Biological Weapons, Tularemia,...
The human acetylcholinesterase (hAChE) gene was cloned into the pHLsec expression vector. The recombinant enzyme (rhAChEmD) was expressed on a large scale in adherent 293T cells. It was secreted as a monomeric species, purified by affinity chromatography, and deglycosylated with PNGase F. A crystallization screen, using the Mosquito crystallization robot, identified conditions for formation of diffraction-quality crystals, in 0.025% dichloromethane/12% PEG 20,000/0.1M imidazole, pH7.0. The...
Topics: DTIC Archive, WEIZMANN INST OF SCIENCE REHOVOT (ISRAEL), *ACETYLCHOLINESTERASE, *NERVE AGENTS,...
This report examines fundamental processes involving the interaction of nerve agents with solid surfaces using accurate electronic structure methods. The objective is to describe surface interactions and low energy electronic states accurately and to identify factors that affect desorption energies and kinetics, solvation of nerve agents by water and the spectral features of adsorbed nerve agents. Understanding exactly how these molecules interact with organic films and oxide surfaces is the...
Topics: DTIC Archive, Whitten,Jerry L, Benedict College Columbia United States, nerve agents, aDsorption,...
The purpose of this research was 2-fold. The first specific aim was to genetically engineer, express, and validate 2 novel biopharmaceutical fusion proteins, designated AGT-185 and AGT-186. Both proteins are fusion proteins of human paraoxonase (PON)-1 variants and a genetically engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The 2 proteins are intended for development as new treatments of the brain in organophosphate chemical nerve gas attacks. The second...
Topics: DTIC Archive, ARMAGEN TECHNOLOGIES INC SANTA MONICA CA, *PROTEINS, NERVE AGENTS, MONOCLONAL...
This is a proposal to develop novel, mechanism-based therapies for the treatment of organophosphate (OP) nerve agent-induced seizures. We proposed to study the effects of organophosphates anmuscarinic agonists on glutamatergic transmission, and on intrinsic excitability of principal hippocampal neurons test the hypothesis that cholinergic stimulation enhances excitatory synaptic transmission and increases and excitability (Aims 1 & 2). We have completed experiments 1.1-1.4 and 2.1-2.2 as...
Topics: DTIC Archive, VIRGINIA UNIV CHARLOTTESVILLE, *EPILEPSY, *NERVE AGENTS, CHOLINERGIC NERVES,...
This project focuses on the development of highly effective non-chromatographic methods for purifying recombinant proteins and enzymes. This report covers work at Ohio State University, which focuses on the further optimization of the purification technology in the PI s new laboratory. A key aspect of the technology involves the use of a self-cleaving protein module, which can be used to make any purification tag self-cleaving. By combining this module with a variety of purification tags, we...
Topics: DTIC Archive, OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS, *ENZYMES, *PROTEINS, BIOCHEMISTRY,...
The current regimen for treating nerve agent poisoning does not sufficiently suppress the excitotoxic activity that causes severe brain damage, especially in cases where treatment is delayed and nerve agent-induced status epilepticus develops. New therapeutic targets are required to improve survivability and minimize neuropathology after irreversible acetylcholinesterase inactivation. Earlier studies have shown that systemic delivery of adenosine agonists decreases nerve agent lethality;...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, *NERVE...
Organophosphate nerve agents inhibit the enzyme acetyl cholinesterase (AChE), which is involved in nerve signal transduction, by forming covalent adducts with its catalytic serine residue. AChE adducts with soman and sarin nerve agents undergo dealkylation, a process known as aging, within a few minutes and a few hours, respectively. This transformation is detrimental because it precludes reactivation of AChE with known oxime-based antidotes. Here, we designed a beta-aminoalcohol molecule for...
Topics: DTIC Archive, Khavrutskii,Ilja V, Biotechnology High Performance Computing Frederick United States,...
The long-term objective of this effort is to develop a generic gene shuffling-based technology to rapidly screen libraries of 1010 proteins/peptides encoded by DNA libraries, for identifying biomolecules that can intercept both existing and emerging organophosphate-based chemical warfare nerve agents (CWNA). The specific milestones for year 1 were (a) Proof of concept for the proposed technology; (b) Generation of 4-6 libraries based on recombinant PON1 and PON3 based on gene shuffling and...
Topics: DTIC Archive, WEIZMANN INST OF SCIENCE REHOVOT (ISRAEL), *NERVE AGENTS, *CATALYSIS, *MOLECULES,...
High loadings of nerve agent-related phosphonic acids adsorbed on ?-Al2O3 and concrete examined by 31P MAS NMR and high-field 27Al MAS NMR reveal the presence of several phosphonate-surface binding modes and greatly improved resolution of multiple AlIV sites. Some of the resolved AlIV sites are sensitive to surface hydroxylation/dehydroxylation are attributed to surface AlIV-OH groups (apparently having been observed for the first time). Although the number of surface AlIV sites detected by...
Topics: DTIC Archive, NEW YORK STRUCTURAL BIOLOGY CENTER INC NEW YORK NY, *ALUMINATES, *CONCRETE,...
We report the synthesis and characterization of a water-stable zirconium metal-organic framework(MOF), NU-1003, featuring the largest mesoporous aperture known for a zirconium MOF. This material has been used to immobilize the nerve agent hydrolyzing enzyme, organophosphorus acid anhydrolase (OPAA). The catalytic efficiency of immobilized OPAA in nanosized NU-1003 is significantly increased compared to that of OPAA immobilized in microsized NU-1003 and even exceeds that of the free OPAA enzyme....
Topics: DTIC Archive, Li,Peng, NORTHWESTERN UNIV EVANSTON IL EVANSTON United States, Zirconium compounds,...
A major obstacle in the utility of enzymes for decontamination purposes is their sensitivity to their surrounding environment. Enzymes are only catalytically active within a narrow range of conditions including pH and temperature. Sensitivity to pH is of particular importance in hydrolysis reactions due to the generation of acidic products. In the enzymatic hydrolysis of nerve agents, to prevent inaction of the enzyme prior to complete conversion of the toxin, tight control of pH over the full...
Topics: DTIC Archive, Kaar, Joel L, PITTSBURGH UNIV PA, *NERVE AGENTS, *DETOXIFICATION, DECONTAMINATION,...
This paper highlights cleanup efforts under the Defense Environmental Restoration Program at sites contaminated or suspected to be contaminated with chemical warfare materiel. Chemical warfare materiel are munitions or containers holding blister agents, nerve agents, blood agents, and choking agents. Also of concern are soil and scrap contaminated with these agents, or soil contaminated with decontaminating solutions. This paper outlines the history of military use that led to contamination. It...
Topics: DTIC Archive, CORPS OF ENGINEERS HUNTSVILLE AL, *CHOKING AGENTS, *NERVE AGENTS, *CHEMICAL WARFARE,...
The goal of this project is to evaluate the extent to which PONsub1192/Gulf War (GW)-related exposure interactions contribute to the risk for Gulf War Illness (GWI), as defined by the Centers for Disease Control and Prevention(CDC) and Kansas case definitions in a large sample of GW veterans. Specifically, we will: (1) determine the associations between GWI and GW-related exposures with the potential for cholinergic effects (e.g., personal pesticide use, exposure to OP nerve agents) in...
Topics: DTIC Archive, Chao, Linda, NCIRE San Francisco United States, PERSIAN GULF SYNDROME, TOXIC HAZARDS,...
We investigated the ability of the engineered paraoxonase-1 variants G3C9, VII-D11, I-F11 and VII-D2 to afford protection against paraoxon intoxication. Paraoxon is the toxic metabolite of parathion, a common pesticide still in use in many developing countries. An in vitro investigation showed that VII-D11 is the most efficient variant at hydrolyzing paraoxon for the enzyme expressed via adenovirus infection of 293A cells and mice, respectively. Compared to the G3C9 parent scaffold, VII-D11 is...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD,...
To investigate the ability of human senescence marker protein 30 (SMP30) to offer protection against chemical warfare nerve agents in vivo, we produced a recombinant human SMP30 fusion protein with a hemaglutinin tag expressed using an adenovirus (AD-SMP30). A single intravenous injection of Ad-SMP30 into mice transduced the expression of SMP30 fusion protein in a dose and time dependant manner in the liver and diaphragm, but not in the plasma or other tissues examined in mice. Expression of...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, *NERVE...
Novel Approach: Non-woven Technology. Research program utilizes needle-punching technology to develop chemical warfare protective substrates. Important characteristics for chemical protective substrates include: (1) Toxic chemical adsorption; (2) Next-to-Skin friendliness; (3) Breathability. Characteristics conflict with each other -- Non-woven technology could be the solution.
Topics: DTIC Archive, Sata, Utkarsh, TEXAS TECH UNIV LUBBOCK, *DECONTAMINATION, *CHEMICAL WARFARE,...
Chemical nerve agents consist of organophosphates that irreversibly inhibit the enzyme acetylcholinesterase within minutes, resulting in death by asphyxiation unless immediate medical support is provided. Currently, different methods for the destruction of large stockpiles of these agents are under evaluation. A method of destruction proposed by the Lawrence Berkeley National Laboratory (LBNL; Berkeley, CA) sought the development of a recombinant Escherichia coli strain that utilizes the nerve...
Topics: DTIC Archive, Gibbons,Jennifer A, Director, ECBC Springfield United States, Escherichia coli, gb...
This Test Operations Procedure (TOP) provides the current standard methods for testing the permeation of low volatility chemicals, such as persistent nerve agent (VX), through swatches of materials. Swatches can be taken from clothing or equipment that is new, with or without pretreatment(s), and that was previously subjected to periods of wear under varying conditions of field use, storage, and/or environmental exposure(s). These procedures are designed to be used as part of an overall...
Topics: DTIC Archive, U.S. Army Dugway Proving Ground Dugway United States, CHEMICAL WARFARE AGENTS, NERVE...
A structure-activity analysis was used to evaluate the variation in oxime efficacy of 2-PAM, obidoxime, HI-6 and ICD585 against nerve agents. In vivo oxime protection and in vitro oxime reactivation were used as indicators of oxime efficacy against VX, sarin, VR and cyclosarin. Analysis of in vivo oxime protection was conducted with oxime protective ratios (PR) from guinea pigs receiving oxime and atropine therapy after sc administration of nerve agent. Analysis of in vitro reactivation was...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, *NERVE...
The aims of this project were to structurally study and bioengineer thermostable prolidases from Pyrococcus furiosus (Pf) and horikoshii (Ph) to enable their use for oganophosphorus nerve agent detoxification. Pf prolidase contains one dinuclear Co metal-center/monomer and has optimal activity at 100 deg C, exhibiting no activity without Co2+ or at temperatures 50 deg C. Requirement for metal ions is characteristic of all organophosphorus nerve agent hydrolases and results from these enzymes...
Topics: DTIC Archive, NORTH CAROLINA STATE UNIV AT RALEIGH OFFICE OF CONTRACTS AND GRANTS, *MICROORGANISMS,...
Stereoisomers are molecules with the same sequence of bonded atoms but a different orientation of these atoms in space, and enantiomers are non-superimposable stereoisomers. Enantiomers have the same chemical and physical properties except for their ability to rotate linearly polarized light in opposite directions. Nearly all previous research with chemical warfare nerve agents has been conducted using a mixture containing equal amounts of each stereoisomer or enantiomer, but it has been...
Topics: DTIC Archive, Wright,Linnzi K, Director, ECBC APG United States, rodents, nerve agents, laboratory...
An automated air sampling and analysis system was built around the OPTIC GC injector. The system was successfully employed for the unattended near real time monitoring and analysis of soman vapor. With respect to the previously employed system several substantial improvements were reached with the current system. the OPTIC GC injector, through its design has markedly better analytical performance, i.e. it allows better quantification of agent concentration and it is clearly more flexible in...
Topics: DTIC Archive, Harteveld, J L, TNO DEFENSE SECURITY AND SAFETY RIJSWIJK (NETHERLANDS), *NERVE...
ADD392124 was identified by the Anticonvulsant Screening Program as being able to control benzodiazepine-resistant status epilepticus seizures. We evaluated the ability of ADD392124 to control seizures induced by the nerve agent soman. Rats were exposed to a convulsant dose of soman. Seizures were allowed to develop, and the standard treatment for nerve agent intoxication--atropine, 2-PAM (an oxime cholinesterase reactivator), and diazepam (a benzodiazepine)--was administered at either 5 or 20...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD,...
This study evaluated the anticonvulsant effectiveness of midazolam to stop seizures elicited by the nerve agent soman when midazolam was administered by different routes (intramuscular, intranasal or sublingual) at one of two different times after the onset of seizure activity. Guinea pigs previously prepared with cortical electrodes to record brain electroencephalographic activity were pre-treated with pyridostigmine (0.026 mg/kg, intramuscularly) 30 min. before challenge with a...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, *GD AGENT,...
Herein we present a short synthetic method for the generation of 4-amino-2-(diethylaminomethyl)phenol (ADOC) analogs 4a-c and 6a-c from commercially available and inexpensive acetaminophen (2). The method was used to prepare and make available a pilot-scale library of analogs for in vitro biological evaluation in the USAMRICD's multi-agent screen for nerve agent-inhibited acetylcholinesterase reactivation. Our hope is that this method will facilitate SAR studies directed toward the development...
Topics: DTIC Archive, Canter,Zachary, U.S. Army Medical Research Institute of Chemical Defense Aberdeen...
This is a proposal to develop novel, mechanism-based therapies for the treatment of organophosphate (OP) nerve agent-induced seizures. OP nerve agents, such as sarin, soman and VX act by central and peripheral cholinesterase inhibition and enhance cholinergic transmission. In experimental animals, aknown nerve agents produce convulsive seizures and status epilepticus within minutes of exposure. Proposed time table for the Year 1was to a) Obtain regulatory approval for use of animals and obtain...
Topics: DTIC Archive, NORTH CAROLINA UNIV AT CHARLOTTE, *EPILEPSY, ANIMALS, CHOLINERGIC NERVES, CONVULSIVE...
Over the past several years the ultimate goal in our laboratories has been to develop new strategies for the transformation of the a variety of lignocellulosic resources into value-added materials and chemicals based on environmentally sustainable and economically viable processing platforms, with ILs playing a central role in these transformations. To this effect we have accumulated a thorough understanding of the way cellulose, lignin and hemicelluloses interact as well as whole wood...
Topics: DTIC Archive, NORTH CAROLINA STATE UNIV AT RALEIGH DEPT OF CHEMISTRY, *ADSORBENTS, *CHEMICAL...
Sensing based on carbon nanotube (CNT) materials has been as area of interest since the material's discovery by Iijima in 1991 (Nature 1991, 354, 56?58), and an active area of research once CNT availability began to increase via the innovations of Smalley and others (Chem Phys Lett 1995, 243, 49?54). The work presented in this report was conducted at Rice University under contract W911NF-11-1-0249. Here, it is shown that the use of high weight percentage CNT medium density polyethylene (MDPE)...
Topics: DTIC Archive, RICE UNIV HOUSTON TX DEPT OF MECHANICAL ENGINEERING AND MATERIALS SCIENCE, *CARBON...
This research and development project entitled Nerve Agent Sensing Biopolymer Wipe is directed at developing a simple-to-use enzyme-containing sensor for detecting nerve agent contamination at surfaces, in air and in solution, and to provide a tool for early and accurate identification of the chemical agents. The objective of this research effort consists of presenting a prototype to the end-user community, which is highly sensitive, easy to use, and accurate. The Agentase nerve agent...
Topics: DTIC Archive, Erbeldinger, Markus, AGENTASE PITTSBURGH PA, *NERVE AGENTS, *CHEMICAL AGENT...
Two compounds, 4-methylthiobenzaldehyde oxime and 4-thiobenzaldehyde oxime, were synthesized for use as capture molecules for applications using surface-enhanced Raman as a means of detection. The thioether moiety was successfully attached to the silver nanoparticle substrate as evidenced by the change in the resulting spectrum. The oxime was shown to be reactive toward the nerve agent GD (Soman) in basic solution, as monitored by (31)P NMR.
Topics: DTIC Archive, CALIFORNIA UNIV SANTA BARBARA, *OXIMES, *NERVE AGENTS, *RAMAN SPECTROSCOPY, THIOLS,...
We report the use of carbon nanotubes as a sensor for chemical nerve agents. Thin-film transistors constructed from random networks of single-walled carbon nanotubes were used to detect dimethyl methylphosphonate (DMMP), a simulant for the nerve agent sarin. These sensors are reversible and capable of detecting DMMP at sub-ppb concentration levels, and they are intrinsically selective against interferent signals from hydrocarbon vapors and humidity. We provide additional chemical specificity by...
Topics: DTIC Archive, NAVAL RESEARCH LAB WASHINGTON DC, *CARBON NANOTUBES, *CHEMICAL AGENT DETECTORS,...
Soman, an organophosphorous (OP) compound, is a chemical warfare agent thatirreversibly inhibits acetylcholinesterase in the periphery and central nervous system.Soman induces status epilepticus leading to brain damage associated with long-termcognitive and behavioral deficits. Current countermeasures are only effective whenadministered shortly after exposure to nerve agents and there are no therapies that protectagainst the long-term cognitive and behavioral impairments, which call for the...
Topics: DTIC Archive, Piermartiri,Tetsade C, Uniformed Services University Of The Health Sciences Bethesda...
Chemical nerve agents such as VX (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate), RVX (S-[2-(diethylamino)ethyl] O-isobutyl-methylphosphonothioate), and GB (isopropyl methylphosphonofluoridate) exist as a mixture of two enantiomers. A Lux 5u Cellulose-1 normal-phase chiral liquid chromatography column (Phenomenex; Torrance, CA) was used to separate the enantiomers for all V and G agents within 15 min. Atmospheric pressure chemical ionization mode was used for liquid...
Topics: DTIC Archive, Bae,Sue Y, Edgewood Chemical Biological Center Aberdeen Proving Ground United States,...
We are continuing to examine a number of neuroprotective agents in an MPTP model of PD. We are also continuing to utilize metabolomic profiling to identify novel biomarkers for PD and to investigate whether these occur in animal models of PD. We are continuing to develop and characterize a new animal model of PD by making a knock out of PlNK1, a nuclear encoded kinase localized to mitochondria, and which causes autosomal recessive PD. We have completed a study of the effects of human...
Topics: DTIC Archive, Beal, M F, CORNELL UNIV MEDICAL COLL (WEILL) NEW YORK, *PARKINSONS DISEASE,...
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...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD,...
Catalyzed based olefin metathesis is a very valuable and useful tool in synthetic organic chemistry. Our research goals consisted of employing olefin metathesis in the synthesis of peptidomimetics, and studying the feasibility of this method in dynamic combinatorial chemistry and molecular imprinting of nerve agents. One of the approaches to the development of peptidomimetics is to attach biologically significant functional groups, such as amino acid side chains, to a scaffold. Grubbs' second...
Topics: DTIC Archive, Low, Tammy K, FLORIDA UNIV GAINESVILLE DEPT OF CHEMISTRY, *SYNTHESIS(CHEMISTRY),...
MMB-4, an oxime that can reactivate acetylcholinesterase (AChE) after inhibition by some nerve agents, is currently in advanced development for potential human use as a replacement for the currently fielded oxime 2-PAM. It has long been known that while certain oximes can be therapeutically effective against OP intoxication at appropriate doses, they can also act as reversible inhibitors of AChE at higher doses. This study was designed to test the hypothesis that the unexpected toxicity of...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD,...
An optical detection method is presented that is designed to detect and identify the presence of macromolecular gas species (e.g., organophosphate-based nerve agent simulants) at trace level concentrations. The technique is based on a modified version of conventional laser photoacoustic (PA) spectroscopy, in which optical absorption is typically measured using a single laser source. We demonstrate the ability to simultaneously measure multiple absorption-related parameters that serve as a...
Topics: DTIC Archive, ARMY RESEARCH LAB ADELPHI MD, *ACOUSTIC SIGNALS, *CHEMICAL AGENT SIMULANTS, *NERVE...
Studies on the structure of acetylcholinesterase (AChE) as a target for organophosphate toxicity continue and have resulted in several leads of significance. First, we have completed the first phase of studies of the structural determinants on the enzyme responsible for inactivation and oxime reactivation. The oxime reactivation studies reveal mutations whereby reactivation can be accelerated some 100-fold, and the combination oxime-mutant AChE shows promise as a prophylactic agent or antidote....
Topics: DTIC Archive, Taylor, Palmer, CALIFORNIA UNIV SAN DIEGO LA JOLLA, *INHIBITION,...
Triethylphosphate and two diastereoisomers of Opinacolyl methylphosphonic acid, the primary hydrolysis product of the nerve agent soman, were identified in an organic solvent with a single 31P-1H heteronuclear Overhauser effect spectroscopy (HOESY) spectrum correlating phosphorus nuclei to their J-coupled protons. An analogous heteronuclear multiple bond correlation experiment is also presented to demonstrate the superiority of HOESY for detecting long-range 3lP-1H pairs. This superiority...
Topics: DTIC Archive, EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD RESEARCH AND...
Pre-treatment of American troops with pyridostigmine bromide (PB) has been advocated as an effective way to counteract the potential lethal effect of nerve-agent exposure during military operations. This policy is based on experimental evidence indicating that PB provides partial protection to animals exposed to soman. The protecting mechanism of PB involves a temporary inhibition of the end-plate acetylcholinesterase (AChE) which prevents an ensuing irreversible inhibition induced by a nerve...
Topics: DTIC Archive, Maselli, Ricardo A, CALIFORNIA UNIV DAVIS, *NERVE AGENTS, *PYRIDOSTIGMINE BROMIDE,...
This study was conducted to investigate the biodegradation potential of neutralized organophosphorus nerve agents: O-ethyl-S-(2-diisopropyl-aminoethyl) methylphosphonothioate (VX), Sarin (GB), Soman (GD), and O-cyclohexyl methylphosphonofluoridate (GF). Removing labile leaving groups from these compounds can be accomplished chemically (e.g. alkali) or enzymatically (by a variety of hydrolases) resulting in stable ionic methylphosphonate esters. Glyphosate utilizing Burkholderia caryophilli...
Topics: DTIC Archive, Elashvili, Ilya, EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD,...
Project Summary: The long-term objective of this effort is to develop a generic gene shuffling-based technology to rapidly screen libraries of 1010 proteins/peptides encoded by DNA libraries, for identifying biomolecules that can intercept both existing and emerging organophosphate-based chemical warfare nerve agents (CWNA). The tasks to be performed at the Weizmann Institute to achieve the major goals of the Center current year are outlined below: #1. Screening for paraoxon- parathion-...
Topics: DTIC Archive, WEIZMANN INST OF SCIENCE REHOVOT (ISRAEL), *CRYSTALLOGRAPHY, *INTOXICATION, *NERVE...
VX and Russian V-agent (VR) are the two most widely known V-agents; however, others also exist. One of these is o-ethyl S-[2-(diethylamino)-ethyl]methylphosphono-thioate, or VM. These studies investigated the lethality of VM in guinea pigs following subcutaneous challenge and determined the effectiveness of current U.S. medical countermeasures atropine sulfate, pralidoxime chloride (2PAM) and diazepam with and without pretreatment with pyridostigmine bromide. The 24 hr median lethal dose (MLD)...
Topics: DTIC Archive, ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD,...
This manual is a reference handbook published for use as a chemical agent information source by personnel performing services within chemical agent areas.
Topics: DTIC Archive, EDGEWOOD ARSENAL ABERDEEN PROVING GROUND MD, *CHEMICAL WARFARE AGENTS, *HANDBOOKS,...
Immunization against nerve agents constitutes the first instance that vaccination against a synthetic chemical, not occurring in nature, has been found to be pharmacologically effective. It is hoped that immunohistochemically monitored refinements will make the procedure clinically safe.
Topics: DTIC Archive, Sternberger, Ludwig A, EDGEWOOD ARSENAL ABERDEEN PROVING GROUND MD, *NERVE AGENTS,...
Nanotechnology has opened a wide range of opportunities having potential impacts in areas as diverse as medicine and consumer products. In collaboration with researchers at the University of Toledo (UT), Air Force Institute of Technology (AFIT) scientists are exploring the possibility of using a nanoscale organic matrix to detect organophosphate (OP) nerve agents. Current techniques for detecting OP compounds are expensive and time consuming. Developing a nanoscale organic matrix sensor would...
Topics: DTIC Archive, AIR UNIV MAXWELL AFB AL AIR FORCE RESEARCH INST, *NANOTECHNOLOGY, *NERVE AGENTS,...
This report documents the initial phases (model development) of a DoD Challenge project investigating the interactions of organophosphorus compounds with acetylcholinesterase. This project entails characterization of the structural features, which lie al the heart of the interaction between novel organophosphorus compounds (or other more reversible inhibitors) and the enzyme acetylcholinesterase. Large biological systems present inherent difficulties to the modeling community. We are using...
Topics: DTIC Archive, Wright, J B, ARMY SOLDIER AND BIOLOGICAL CHEMICAL COMMAND NATICK MA, *NERVE AGENTS,...
Nerve agent (organophosphate) detection, symptom identification, and treatment has long been a priority for US military forces, agent storage depots, demil facilities, and now is becoming an issue at formerly used defense sites (FUDS) or in the case of Rocky Mountain Arsenal (RMA), a former production facility, where these agents had been stored, tested, or disposed of and which is currently undergoing environmental remediation. Protecting workers who may be potentially exposed to acute or...
Topics: DTIC Archive, ROCKY MOUNTAIN ARSENAL DENVER CO, *NERVE AGENTS, *ANTIDOTES, PROTECTION, POISONING,...