Tobacco-specific N'-nitrosamines (TSNA) are a unique class of systemic organ-specific carcinogens. The TSNA are formed by N-nitrosation of nicotine and of the minor tobacco alkaloids after harvesting of tobacco and during smoking. The N-nitrosation of anatabine leads to N'-nitrosoanatabine (NAT; 1-nitroso-1,2,3,4-tetrahydro-2,3'-bipyridyl) which requires in-depth assays in laboratory animals other than the rat. Furthermore, delineation of its tissue distribution and metabolism is needed for structure:activity comparisons with other TSNA and for the assessment of potential human risk from this TSNA. We have, therefore, synthesized (+)[5-3H]NAT. 5-Bromo-3-pyridine-carboxaldehyde was condensed with ethyl carbamate prior to Diels-Alder reaction with 1,4-butadiene to give the racemic anatabine ring system. Hydrolysis followed by reduction with LiAlT4 and nitrosation, led to (+)[5-3H]NAT (60 percent yield, specific activity 266 mCi/mmol, radiochemical purity of >99 percent).

Dantrolene is a drug that suppresses intracellular Ca2+ release from sarcoplasmic reticulum in normal skeletal muscle and is used as a therapeutic agent in individuals susceptible to malignant hyperthermia. Though its precise mechanism of action has not been elucidated, we have identified the N-terminal region (amino acids 1-1400) of the skeletal muscle isoform of the ryanodine receptor (RyR1), the primary Ca2+ release channel in sarcoplasmic reticulum, as a molecular target for dantrolene using the photoaffinity analog [3H]azidodantrolene(1). Here, we demonstrate that heterologously expressed RyR1 retains its capacity to be specifically labeled with [3H]azidodantrolene,indicating that muscle specific factors are not required for this ligand-receptor interaction. Synthetic domain peptides of RyR1, previously shown to affect RyR1 function in vitro and in vivo, were exploited as potential drug binding site mimics and used in photoaffinity labeling experiments. Only DP1 and DP1-2, peptide s containing the amino acid sequence corresponding to RyR1 residues 590-609, were specifically labeled by [3H]azidodantrolene. A monoclonal anti-RyR1 antibody which recognizes RyR1 and its 1400 amino acid N-terminal fragment, recognizes DP1 and DP1-2 in both Western blots and immunoprecipitation assays, and specifically inhibits [3H]azidodantrolene photolabeling of RyR1 and its N-terminal fragment in sarcoplasmic reticulum. Our results indicate that synthetic domain …

The purpose of this study is to quantify the flow and transport model uncertainty for the Central Nevada Test Area (CNTA). Six parameters were identified as uncertain, including the specified head boundary conditions used in the flow model, the spatial distribution of the underlying welded tuff unit, effective porosity, sorption coefficients, matrix diffusion coefficient, and the geochemical release function which describes nuclear glass dissolution. The parameter uncertainty was described by assigning prior statistical distributions for each of these parameters. Standard Monte Carlo techniques were used to sample from the parameter distributions to determine the full prediction uncertainty. Additional analysis is performed to determine the most cost-beneficial characterization activities. The maximum radius of the tritium and strontium-90 contaminant boundary was used as the output metric for evaluation of prediction uncertainty. The results indicate that combining all of the uncertainty in the parameters listed above propagates to a prediction uncertainty in the maximum radius of the contaminant boundary of 234 to 308 m and 234 to 302 m, for tritium and strontium-90, respectively. Although the uncertainty in the input parameters is large, the prediction uncertainty in the contaminant boundary is relatively small. The relatively small prediction uncertainty is primarily due to the …

The KEK Accelerator Test Facility (ATF) damping ring is a prototype low emittance source for the NLC/JLC linear collider. To achieve the goal normalized vertical emittance {gamma}{var_epsilon}{sub {gamma}} = 20 nm-rad, magnet placement accuracy better than 30 mm must be achieved. Accurate beam-based alignment (BBA) is required. The ATF arc optics uses a FOBO cell with two horizontally focusing quadrupoles, two sextupoles and a horizontally defocusing gradient dipole, all of which must be aligned with BBA. BBA at ATF uses the quadrupole and sextupole trim windings to find the trajectory through the center of each magnet. The results can be interpreted to assess the accuracy of the mechanical alignment and the beam position monitor offsets.

A new Detonation Profile Test (DPT) was developed to measure simultaneously the detonation wave breakout profile and the average detonation velocity at the breakout surface. The test evaluated small cylindrical samples with diameter up to 19.08 mm and length up to 33 mm. The experiment involved initiating a LX-17 cylindrical specimen and recording the wave breakout using a fast streaking electronic camera. The initiation was done using a PBX-9407 pellet (1.630 g/cm{sup 3}), which has a Chapman-Jouguet (C-J) pressure close to that of LX-17. The acceptor breakout surface had a 2 mm wide by 1 mm deep groove that provided a step in the recorded breakout profile for velocity determination. A 532-nm laser light illuminated the specimen surface. A streak camera looking perpendicular to the groove, recorded the extinction of the laser light as the detonation wave emerged from the surface. This technique provided a high-resolution spatial and temporal profile of the wave curvature as well as accurate timing of the propagating wave over the last millimeter of the sample. The measured groove depth and recorded travel time were then used to calculate the average detonation wave velocity. Results for 12.7 mm diameter unconfined LX-17 charges showed detonation velocity in …

A high priority has been given to investigating the vitrification of three specific nuclear wastes in iron phosphate glasses (IPG). These wastes, which were recommended by the Tank Focus Area (TFA) group of Hanford, are poorly suited for vitrification in the currently DOE-approved borosilicate (BS) glasses. They include (1) a sodium bearing waste (SBW) at INEEL, (2) a high chrome waste (HCW) at Hanford, and (3) a high sodium/sulfate waste (HSSW), also known as low activity waste (LAW) at Hanford. A simulated composition for each waste, which was simplified by neglecting components present in quantities < 0.4 wt%, was used in the present investigation.