Gene/Protein Disease Symptom Drug Enzyme Compound
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As the genomes of mammalian species become sequenced and gene functions are ascribed, the use of differential gene expression (DGE) to evaluate organ function will become common in the experimental evaluation of new drug therapies. The ability to translate this technology into useful information for human exposures depends on tissue sampling that is impractical or generally not possible in man. The possibility that the DGE of nucleated cells, reticulocytes, or platelets in blood may present the necessary link with target organ toxicity provides an opportunity to correlate preclinical with clinical outcomes. Adriamycin is highly effective alone and more frequently in combination with other chemotherapeutic agents in the treatment of a variety of susceptible malignancies. Adriamycin-induced cardiomyopathy was examined as an endpoint to measure the utility of DOE on whole blood as a predictor of cardiac toxicity. Statistically significant gene changes were observed between relevant blood and cardiac gene profiles that corroborated the accepted mechanisms of toxicity (oxidative stress, effects on carnitine transport, DNA intercalation). There were, however, clear indications that other target organs (bone marrow and intestinal tract) were affected. The divergent expression of some genes between the blood and the heart on day 7 may also indicate the timing and mechanism of development of the cardiomyopathy and confirm current therapeutic approaches for its prevention. The data demonstrate that whole blood gene expression particularly in relation to oxidative stress, in conjunction with standard hematology and clinical chemistry, may be useful in monitoring and predicting cardiac damage secondary to adriamycin administration. Appendices A & B, referenced in this paper, are not printed in this issue of Toxicologic Pathology. They are available as downloadable text files at http://taylorandfrancis.metapress.com/openurl.asp?genre=journal&issn=0192-6233. To access them, click on the issue link for 30(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org.
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PMID:Correlation of simultaneous differential gene expression in the blood and heart with known mechanisms of adriamycin-induced cardiomyopathy in the rat. 1218 37

Dynamic behavior of an analog-to-digital converter (ADC) based on diffractive optical element(s) (DOE)(s) was studied and found to be in agreement with predictions. The analog signal was translated to an angular deflection of a laser beam by means of an acousto-optic (AO) cell. The number of bits in this experimental demonstration was three, using an eight-element DOE array. The maximum sample rate was found to be 2.5 MS/s, the limiting factor being the transit time for the acoustic wave across the width of the laser beam in the AO cell. The study is intended as a first dynamic demonstration of a proposed ADC scheme previously demonstrated in a quasi-static version. The full potential of the ADC scheme will require the use of a fast tunable diode laser to replace the AO deflection scheme used here.
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PMID:Dynamic demonstration of diffractive optic analog-to-digital converter scheme. 1254 6

ABSTRACT The Fort St. Vrain Nuclear Generating Station was a one-of-its-kind High Temperature Gas Cooled Reactor located near Denver, CO. Due to operational difficulties, the reactor was permanently shut down in August 1989. Plans to ship the spent reactor fuel to Idaho were thwarted by the Governor of Idaho. The inability to ship the spent reactor fuel offsite necessitated the construction of an Independent Spent Fuel Storage Installation (ISFSI) in order to proceed with the decommissioning of the reactor. After loading the ISFSI, decommissioning of the reactor was initiated and successfully completed. At the same time, the site was repowered using natural gas. As part of a settlement with the owner of the reactor, the U.S. Department of Energy agreed to take title to the spent fuel in the ISFSI and obtain an NRC license for the facility. The license for the ISFSI was transferred to the DOE in June 1999. Day-to-day operations of the ISFSI are accomplished by the DOE's Maintenance and Operations contractor, Bechtel Babcock Wilcox Idaho (BBWI). BBWI also operates the Three Mile Island Unit 2 ISFSI in Idaho for the DOE. This paradigm for ISFSI operations has been highly successful and is expandable to additional ISFSIs that may come under the jurisdiction of the DOE.
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PMID:Fort St. Vrain-A DOE Success Story. 1255 31

The Fort St. Vrain Nuclear Generating Station was a one-of-its-kind High Temperature Gas Cooled Reactor located near Denver, CO. Due to operational difficulties, the reactor was permanently shut down in August 1989. Plants to ship the spent reactor fuel to Idaho were thwarted by the Governor of Idaho. The inability to ship the spent reactor fuel offsite necessitated the construction of an Independent Spent Fuel Storage Installation (ISFSI) in order to proceed with the decommissioning of the reactor. After loading the ISFSI, decommissioning of the reactor was initiated and successfully completed. At the same time, the site was repowered using natural gas. As part of a settlement with the owner of the reactor, the U.S. Department of Energy agreed to take title to the spent fuel in the ISFSI and obtain an NRC license for the facility. The license for the ISFSI was transferred to the DOE in June 1999. Day-to-day operations of the ISFSI are accomplished by the DOE's Maintenance and Operations contractor, Bechtel Babcock Wilcox Idaho (BBWI). BBWI also operates the Three Mile Island Unit 2 ISFSI in Idaho for the DOE. This paradigm for ISFSI operations has been highly successful and is expandable to additional ISFSIs that may come under the jurisdiction of the DOE.
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PMID:Fort St. Vrain--a DOE success story. 1256 41

The proposed research will investigate two microbial communities that are of direct relevance to Department of Energy interests. One is the microbial community associated with the in situ bioremediation of uranium-contaminated groundwater. The second is a microbial community that harvests energy from waste organic matter in the form of electricity. These studies will address DOE needs for (1) remediation of metals and radionuclides at DOE sites and (2) the development of cleaner forms of energy and biomass conversion to energy. Our previous studies have demonstrated that the microbial communities involved in uranium bioremediation and energy harvesting are both dominated by microorganisms in the family Geobacteraceae and that the organisms in this family are responsible for uranium bioremediation and electron transfer to electrodes. The initial objectives of this study are to (1) describe the genetic potential of the Geobacteraceae that predominate in the environments of interest; (2) identify conserved patterns of gene expression within the Geobacteraceae family in response to a range of environmental conditions; (3) begin to identify mechanisms controlling the expression of key genes related to survival, growth, and activity in subsurface environments and on electrodes; and (4) use the results from subobjectives 1-3 to develop a conceptual model for predicting gene expression of Geobacteraceae in the environments of interest. This will serve as the basis for a subsequent simulation model of the growth and activity of Geobacteraceae in the subsurface and on electrodes.
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PMID:Analysis of the genetic potential and gene expression of microbial communities involved in the in situ bioremediation of uranium and harvesting electrical energy from organic matter. 1262 92

A 5-inch-diameter Frisch Grid gas-proportional ionization chamber was utilized at Brookhaven National Laboratory (BNL) to rapidly characterize and quantify alpha-emitting actinides in unprocessed water, soil, air-filter, urine, and solid matrices. Instrument calibrations for the various matrices were performed by spiking representative samples with National Institute of Standards and Technology traceable isotopes of 230Th, 232U, 236Pu, and 243Am. Detection efficiencies were typically 15-20% for solid matrices (soil, concrete, filters, dry urine) and 45% for mass-less water samples. Instrument background over a 512-channel alpha-energy range of 3-8 MeV is very low at 0.01 cps. At optimum efficiency, minimum detectable levels of 0.56 mBq Kg(-1), 74 mBq L(-1) and 14.8 mBq filter(-1) were achievable for 40 x 10(-6) Kg soil, 1 x 10(-3) L tap water (or urine), and 4.5 cm diameter air-filter samples, respectively, each counted for 60 min. Data and spectra are presented showing the quality of results obtained using untreated samples obtained from the BNL Graphite Research Reactor Decommissioning Project. These samples contained Bq to MBq per gram amounts of (239,240)Pu, 241Am, and/or (234,235/238)U (as well as other beta/gamma emitters). Data and spectra are also presented for a very finely pulverized and homogeneous U.S. DOE/RESL soil reference standard (spiked with 239Pu, 241Am, and 233U) that was used to assess precision, accuracy, and reproducibility. Although this technique has its limitations, the advantages are (1) minimal sample preparation, (2) no separation chemistry required, (3) no chemical or hazardous waste generated, and (4) ability to immediately characterize and quantify alpha-emitting nuclides in most matrices. The benefits of this technique to the BNL/DOE Project Managers were rapid (1-2 d) turn-around times coupled with significant cost savings, as compared to commercial off-site analyses.
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PMID:Rapid analytical technique to identify alpha emitting isotopes in water, air-filters, urine, and solid matrices using a Frisch Grid detector. 1270 48

This exploratory study compares two approaches for involving nonexpert stakeholders in difficult policy choices. Both approaches have as their goal informing members of the public about contaminated sites and involving them in decisions regarding their cleanup. The first approach focuses on technical information and seeks to improve the available knowledge base so that participants can make choices informed by detailed scientific data. This approach is similar in intent to many of the science-based initiatives in public involvement now being undertaken by EPA, DOE, and other federal or state agencies. The second approach, in contrast, focuses on values-oriented information and seeks to improve stakeholders' ability to make difficult choices in light of required tradeoffs across a variety of technical and nontechnical concerns. The results demonstrate that although both approaches help to increase participants' knowledge level, a values-based approach is more successful in terms of helping nonexpert participants to make decisions aboutwhat have historically been viewed as primarily technical problems.
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PMID:Testing alternative decision approaches for identifying cleanup priorities at contaminated sites. 1273 26

This paper investigates the circumstances under which proposed hazardous waste remediation technologies are socially acceptable, that is, considered seriously as options in a public arena. First, it summarizes a conceptual framework that guides investigation and interpretation of site-specific remediation decision-making. Second, it describes an initial application of that framework to the public participation venue of U.S. DOE Site-Specific Advisory Boards. Investigating the attributes of involved parties and of site context highlights technology acceptability as social decision-making that involves technical and technological issues rather than as a process driven by the technology itself.
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PMID:Making decisions about hazardous waste remediation when even considering a remediation technology is controversial. 1273 28

Aqueous solutions of 100 parts per billion (ppb) uranium at pH 7 were treated with granulated activated carbon (GAC) that had been modified with various formulations of hydrophobic aerogels. The composite materials were found to be superior in removing uranium from a stock solution compared to GAC alone evaluated by a modified ASTM D 3860-98 method for batch testing. The testing results were evaluated using a Freundlich adsorption model. The best performing material has parameters of n = 287 and Kf = 1169 compared to n = 1.00, and Kf = 20 for GAC alone. The composite materials were formed by mixing (CH3O)4Si with the hydrophobic sol-gel precursor, (CH3O)3SiCH2CH2CF3 and with specified modifiers, such as H3PO4, Ca(NO3)2, and (C2H5O)3SiCH2CH2P(O)(OC2H5)2, elation catalysts, and GAC in a supercritical reactor system. After gelation, supercritical extraction, and sieving, the composites were tested. Characterization by FTIR and 31P NMR indicate the formation of phosphate in the case of the H3PO4 and Ca(NO3)2 composites and phosphonic acid related compounds in the phosphonate composite. These composite materials have potential application in the clean up of groundwater at DOE and other facilities.
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PMID:Granulated activated carbon modified with hydrophobic silica aerogel-potential composite materials for the removal of uranium from aqueous solutions. 1278 38

States appreciate guidance for activities done infrequently or at only a few locations in the state. For many states, this is the case for decommissioning. Some states have reactors being decommissioned, some DOE sites undergoing cleanup, and some uranium mill or radium sites. Many, however, only occasionally do a small facility cleanup or, once in a great while, a large one. For this reason, most states participated in the readily available MARSSIM training and now recommend its use. For this same reason, the CRCPD Committee on Decontamination and Decommissioning (E24) developed a brief guidance document for state and licensee use.
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PMID:MARSSIM recommended in states' guidance document for decommissioning. 1279 2


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