Stack Flow Rate Changes and the ANSI/N13.1-1999 Qualification Criteria: Application to the Hanford Canister Storage Building Stack

Energy Technology Data Exchange (ETDEWEB)

Flaherty, Julia E. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Glissmeyer, John A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2016-02-29

The Canister Storage Building (CSB), located in the 200-East Area of the Hanford Site, is a 42,000 square foot facility used to store spent nuclear fuel from past activities at the Hanford Site. Because the facility has the potential to emit radionuclides into the environment, its ventilation exhaust stack has been equipped with an air monitoring system. Subpart H of the National Emissions Standards for Hazardous Air Pollutants requires that a sampling probe be located in the exhaust stack in accordance with criteria established by the American National Standards Institute/Health Physics Society Standard N13.1-1999, Sampling and Monitoring Releases of Airborne Radioactive Substances from the Stack and Ducts of Nuclear Facilities.

Essential role of Bordetella NadC in a quinolinate salvage pathway for NAD biosynthesis.

Science.gov (United States)

Brickman, Timothy J; Suhadolc, Ryan J; McKelvey, Pamela J; Armstrong, Sandra K

2017-02-01

Nicotinamide adenine dinucleotide (NAD) is produced via de novo biosynthesis pathways and by salvage or recycling routes. The classical Bordetella bacterial species are known to be auxotrophic for nicotinamide or nicotinic acid. This study confirmed that Bordetella bronchiseptica, Bordetella pertussis and Bordetella parapertussis have the recycling/salvage pathway genes pncA and pncB, for use of nicotinamide or nicotinic acid, respectively, for NAD synthesis. Although these Bordetellae lack the nadA and nadB genes needed for de novo NAD biosynthesis, remarkably, they have one de novo pathway gene, nadC, encoding quinolinate phosphoribosyltransferase. Genomic analyses of taxonomically related Bordetella and Achromobacter species also indicated the presence of an 'orphan' nadC and the absence of nadA and nadB. When supplied as the sole NAD precursor, quinolinate promoted B. bronchiseptica growth, and the ability to use it required nadC. Co-expression of Bordetella nadC with the nadB and nadA genes of Paraburkholderia phytofirmans allowed B. bronchiseptica to grow in the absence of supplied pyridines, indicative of de novo NAD synthesis and functional confirmation of Bordetella NadC activity. Expression of nadC in B. bronchiseptica was influenced by nicotinic acid and by a NadQ family transcriptional repressor, indicating that these organisms prioritize their use of pyridines for NAD biosynthesis. © 2016 John Wiley & Sons Ltd.

Hanford prototype-barrier status report: FY 1995

International Nuclear Information System (INIS)

Gee, G.W.; Ward, A.L.; Gilmore, B.G.; Ligotke, M.W.; Link, S.O.

1995-11-01

Surface barriers (or covers) have been proposed for use at the Hanford Site as a means to isolate certain waste sites that, for reasons of cost or worker safety or both, may not be exhumed. Surface barriers are intende to isolated the wastes from the accessible environment and to provide long-term protection to future populations that might use the Hanford Site. Currently, no ''proven'' long-term barrier system is available. For this reason, the Hanford Site Permanent Isolation Surface-Barrier Development Program (BDP) was organized to develop the technology needed to provide long-term surface barrier capability for the Hanford Site for the US Department of Energy (DOE). Designs have been proposed to meet the most stringent needs for long-term waste disposal. The objective of the current barrier design is to use natural materials to develop a protective barrier system that isolates wastes for at least 1000 years by limiting water, plant, animal, and human intrusion; and minimizing erosion. The design criteria for water drainage has been set at 0.5 mm/yr. While other design criteria are more qualitative, it is clear that waste isolation for an extended time is the prime objective of the design. Constructibility and performance. are issues that can be tested and dealt with by evaluating prototype designs prior to extensive construction and deployment of covers for waste sites at Hanford

NAD-Dependent DNA-Binding Activity of the Bifunctional NadR Regulator of Salmonella typhimurium

OpenAIRE

Penfound, Thomas; Foster, John W.

1999-01-01

NadR is a 45-kDa bifunctional regulator protein. In vivo genetic studies indicate that NadR represses three genes involved in the biosynthesis of NAD. It also participates with an integral membrane protein (PnuC) in the import of nicotinamide mononucleotide, an NAD precursor. NadR was overexpressed and purified as a His-tagged fusion in order to study its DNA-binding properties. The protein bound to DNA fragments containing NAD box consensus sequences. NAD proved to be the relevant in vivo co...

Natural phenomena hazards, Hanford Site, south central Washington

International Nuclear Information System (INIS)

Tallman, A.M.

1996-01-01

This document presents the natural phenomena hazard (NPH) loads for use in implementing DOE Order 5480.28, Natural Phenomena Hazards Mitigation, at the Hanford Site in south-central Washington State. The purpose of this document is twofold: (1) summarize the NPH that are important to the design and evaluation of structures, systems, and components at the Hanford Site; (2) develop the appropriate natural phenomena loads for use in the implementation of DOE Order 5480.28. The supporting standards, DOE-STD-1020-94, Natural Phenomena Hazards Design and Evaluation Criteria for Department of Energy Facilities (DOE 1994a); DOE-STD-1022-94, Natural Phenomena Hazards Site Characteristics Criteria (DOE 1994b); and DOE-STD-1023-95, Natural Phenomena Hazards Assessment Criteria (DOE 1995) are the basis for developing the NPH loads

Permeability of Rickettsia prowazekii to NAD

International Nuclear Information System (INIS)

Atkinson, W.H.; Winkler, H.H.

1989-01-01

Rickettsia prowazekii accumulated radioactivity from [adenine-2,8-3H]NAD but not from [nicotinamide-4-3H]NAD, which demonstrated that NAD was not taken up intact. Extracellular NAD was hydrolyzed by rickettsiae with the products of hydrolysis, nicotinamide mononucleotide and AMP, appearing in the incubation medium in a time- and temperature-dependent manner. The particulate (membrane) fraction contained 90% of this NAD pyrophosphatase activity. Rickettsiae which had accumulated radiolabel after incubation with [adenine-2,8-3H]NAD were extracted, and the intracellular composition was analyzed by chromatography. The cells contained labeled AMP, ADP, ATP, and NAD. The NAD-derived intracellular AMP was transported via a pathway distinct from and in addition to the previously described AMP translocase. Exogenous AMP (1 mM) inhibited uptake of radioactivity from [adenine-2,8-3H]NAD and hydrolysis of extracellular NAD. AMP increased the percentage of intracellular radiolabel present as NAD. Nicotinamide mononucleotide was not taken up by the rickettsiae, did not inhibit hydrolysis of extracellular NAD, and was not a good inhibitor of the uptake of radiolabel from [adenine-2,8-3H]NAD. Neither AMP nor ATP (both of which are transported) could support the synthesis of intracellular NAD. The presence of intracellular [adenine-2,8-3H]NAD within an organism in which intact NAD could not be transported suggested the resynthesis from AMP of [adenine-2,8-3H]NAD at the locus of NAD hydrolysis and translocation

NAD+-Dependent Deacetylase Hst1p Controls Biosynthesis and Cellular NAD+ Levels in Saccharomyces cerevisiae

OpenAIRE

Bedalov, Antonio; Hirao, Maki; Posakony, Jeffrey; Nelson, Melisa; Simon, Julian A.

2003-01-01

Nicotine adenine dinucleotide (NAD+) performs key roles in electron transport reactions, as a substrate for poly(ADP-ribose) polymerase and NAD+-dependent protein deacetylases. In the latter two processes, NAD+ is consumed and converted to ADP-ribose and nicotinamide. NAD+ levels can be maintained by regeneration of NAD+ from nicotinamide via a salvage pathway or by de novo synthesis of NAD+ from tryptophan. Both pathways are conserved from yeast to humans. We describe a critical role of the ...

Structural acceptance criteria for the evaulation of existing double-shell waste storage tanks located at the Hanford site, Richland, Washington

International Nuclear Information System (INIS)

Julyk, L.J.; Day, A.D.; Dyrness, A.D.; Moore, C.J.; Peterson, W.S.; Scott, M.A.; Shrivastava, H.P.; Sholman, J.S.; Watts, T.N.

1995-09-01

The structural acceptance criteria contained herein for the evaluation of existing underground double-shell waste storage tanks located at the Hanford Site is part of the Life Management/Aging Management Program of the Tank Waste Remediation System. The purpose of the overall life management program is to ensure that confinement of the waste is maintained over the required service life of the tanks. Characterization of the present condition of the tanks, understanding and characterization of potential degradation mechanisms, and development of tank structural acceptance criteria based on previous service and projected use are prerequisites to assessing tank integrity, to projecting the length of tank service, and to developing and applying prudent fixes or repairs. The criteria provided herein summarize the requirements for the analysis and structural qualification of the existing double-shell tanks for continued operation. Code reconciliation issues and material degradation under aging conditions are addressed. Although the criteria were developed for double-shell tanks, many of the provisions are equally applicable to single-shell tanks. However, the criteria do not apply to the evaluation of tank appurtenances and buried piping

Preliminary safety criteria for organic watch list tanks at the Hanford site

International Nuclear Information System (INIS)

Webb, A.B.; Stewart, J.L.; Turner, O.A.; Plys, M.G.; Malinovic, B.; Grigsby, J.M.; Camaioni, D.M.; Heasler, P.G.; Samuels, W.O.; Toth, J.J.

1995-11-01

Condensed-phase, rapid reactions of organic salts with nitrates/nitrites in Hanford High Level Radioactive Waste single-shell tanks could lead to structural failure of the tanks resulting in significant releases of radionuclides and toxic materials. This report establishes appropriate preliminary safety criteria to ensure that tank wastes will be maintained safe. These criteria show that if actual dry wastes contain less than 1.2 MJ/kg of reactants reaction energy or less 4.5 wt % of total organic carbon, then the waste will be safe and will not propagate if ignited. Waste moisture helps to retard reactions; when waste moisture exceeds 20 wt %, rapid reactions are prevented, regardless of organic carbon concentrations. Aging and degradation of waste materials has been considered to predict the types and amounts to organic compounds present in the waste. Using measurements of 3 waste phases (liquid, salt cake, and sludge) obtained from tank waste samples analyzed in the laboratory, analysis of variance (ANOVA) models were used to estimate waste states for unmeasured tanks. The preliminary safety criteria are based upon calorimetry and propagation testing of likely organic compounds which represent actual tank wastes. These included sodium salts of citrate, formate, acetate and hydroxyethylethylenediaminetricetate (HEDTA). Hot cell tests of actual tank wastes are planned for the future to confirm propagation tests performed in the laboratory. The effects of draining liquids from the tanks which would remove liquids and moisture were considered because reactive waste which is too dry may propagate. Evaporation effects which could remove moisture from the tanks were also calculated. The various ways that the waste could be heated or ignited by equipment failures or tank operations activities were considered and appropriate monitoring and controls were recommended

Preliminary safety criteria for organic watch list tanks at the Hanford site

Energy Technology Data Exchange (ETDEWEB)

Webb, A.B.; Stewart, J.L.; Turner, O.A. [Westinghouse Hanford Co., Richland, WA (United States); Plys, M.G.; Malinovic, B. [Fauske and Associates, Inc., Burr Ridge, IL (United States); Grigsby, J.M. [G & P Consulting, Inc. (United States); Camaioni, D.M.; Heasler, P.G.; Samuels, W.O.; Toth, J.J. [Pacific Northwest Lab., Portland, OR (United States)

1995-11-01

Condensed-phase, rapid reactions of organic salts with nitrates/nitrites in Hanford High Level Radioactive Waste single-shell tanks could lead to structural failure of the tanks resulting in significant releases of radionuclides and toxic materials. This report establishes appropriate preliminary safety criteria to ensure that tank wastes will be maintained safe. These criteria show that if actual dry wastes contain less than 1.2 MJ/kg of reactants reaction energy or less 4.5 wt % of total organic carbon, then the waste will be safe and will not propagate if ignited. Waste moisture helps to retard reactions; when waste moisture exceeds 20 wt %, rapid reactions are prevented, regardless of organic carbon concentrations. Aging and degradation of waste materials has been considered to predict the types and amounts to organic compounds present in the waste. Using measurements of 3 waste phases (liquid, salt cake, and sludge) obtained from tank waste samples analyzed in the laboratory, analysis of variance (ANOVA) models were used to estimate waste states for unmeasured tanks. The preliminary safety criteria are based upon calorimetry and propagation testing of likely organic compounds which represent actual tank wastes. These included sodium salts of citrate, formate, acetate and hydroxyethylethylenediaminetricetate (HEDTA). Hot cell tests of actual tank wastes are planned for the future to confirm propagation tests performed in the laboratory. The effects of draining liquids from the tanks which would remove liquids and moisture were considered because reactive waste which is too dry may propagate. Evaporation effects which could remove moisture from the tanks were also calculated. The various ways that the waste could be heated or ignited by equipment failures or tank operations activities were considered and appropriate monitoring and controls were recommended.

Determining the Extremes of the Cellular NAD(H) Level by Using an Escherichia coli NAD+-Auxotrophic Mutant ▿

Science.gov (United States)

Zhou, Yongjin; Wang, Lei; Yang, Fan; Lin, Xinping; Zhang, Sufang; Zhao, Zongbao K.

2011-01-01

NAD (NAD+) and its reduced form (NADH) are omnipresent cofactors in biological systems. However, it is difficult to determine the extremes of the cellular NAD(H) level in live cells because the NAD+ level is tightly controlled by a biosynthesis regulation mechanism. Here, we developed a strategy to determine the extreme NAD(H) levels in Escherichia coli cells that were genetically engineered to be NAD+ auxotrophic. First, we expressed the ntt4 gene encoding the NAD(H) transporter in the E. coli mutant YJE001, which had a deletion of the nadC gene responsible for NAD+ de novo biosynthesis, and we showed NTT4 conferred on the mutant strain better growth in the presence of exogenous NAD+. We then constructed the NAD+-auxotrophic mutant YJE003 by disrupting the essential gene nadE, which is responsible for the last step of NAD+ biosynthesis in cells harboring the ntt4 gene. The minimal NAD+ level was determined in M9 medium in proliferating YJE003 cells that were preloaded with NAD+, while the maximal NAD(H) level was determined by exposing the cells to high concentrations of exogenous NAD(H). Compared with supplementation of NADH, cells grew faster and had a higher intracellular NAD(H) level when NAD+ was fed. The intracellular NAD(H) level increased with the increase of exogenous NAD+ concentration, until it reached a plateau. Thus, a minimal NAD(H) level of 0.039 mM and a maximum of 8.49 mM were determined, which were 0.044× and 9.6× those of wild-type cells, respectively. Finally, the potential application of this strategy in biotechnology is briefly discussed. PMID:21742902

Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi

Directory of Open Access Journals (Sweden)

Peter M. Dracatos

2016-09-01

Full Text Available Nicotiana alata defensins 1 and 2 (NaD1 and NaD2 are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An O-mannosyltransferase (pmt knockout (KO mutants (An∆pmtA, An∆pmtB, and An∆pmtC. An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol signalling knockout mutants from the cell wall integrity (CWI and high osmolarity glycerol (HOG mitogen-activated protein kinase (MAPK pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2.

Oxidation of NAD dimers by horseradish peroxidase.

OpenAIRE

Avigliano, L; Carelli, V; Casini, A; Finazzi-Agrò, A; Liberatore, F

1985-01-01

Horseradish peroxidase catalyses the oxidation of NAD dimers, (NAD)2, to NAD+ in accordance with a reaction that is pH-dependent and requires 1 mol of O2 per 2 mol of (NAD)2. Horseradish peroxidase also catalyses the peroxidation of (NAD)2 to NAD+. In contrast, bacterial NADH peroxidase does not catalyse the peroxidation or the oxidation of (NAD)2. A free-radical mechanism is proposed for both horseradish-peroxidase-catalysed oxidation and peroxidation of (NAD)2.

Determining the Extremes of the Cellular NAD(H) Level by Using an Escherichia coli NAD+-Auxotrophic Mutant ▿

OpenAIRE

Zhou, Yongjin; Wang, Lei; Yang, Fan; Lin, Xinping; Zhang, Sufang; Zhao, Zongbao K.

2011-01-01

NAD (NAD+) and its reduced form (NADH) are omnipresent cofactors in biological systems. However, it is difficult to determine the extremes of the cellular NAD(H) level in live cells because the NAD+ level is tightly controlled by a biosynthesis regulation mechanism. Here, we developed a strategy to determine the extreme NAD(H) levels in Escherichia coli cells that were genetically engineered to be NAD+ auxotrophic. First, we expressed the ntt4 gene encoding the NAD(H) transporter in the E. co...

Consequence ranking of radionuclides in Hanford tank waste

International Nuclear Information System (INIS)

Schmittroth, F.A.; De Lorenzo, T.H.

1995-09-01

Radionuclides in the Hanford tank waste are ranked relative to their consequences for the Low-Level Tank Waste program. The ranking identifies key radionuclides where further study is merited. In addition to potential consequences for intrude and drinking-water scenarios supporting low-level waste activities, a ranking based on shielding criteria is provided. The radionuclide production inventories are based on a new and independent ORIGEN2 calculation representing the operation of all Hanford single-pass reactors and the N Reactor

Master schedule for CY-1980 Hanford Environmental Surveillance Routine Program

International Nuclear Information System (INIS)

Blumer, P.J.; Houston, J.R.; Eddy, P.A.

1979-12-01

The current schedule of data collection for the routine environmental surveillance program at the Hanford Site is presented. The enviromental surveillance program objectives are to evaluate the levels of radioactive and nonradioactive pollutants in the Hanford environs, as required in Manual Chapter 0513, and to monitor Hanford operations for compliance with applicable environmental criteria given in Manual Chapter 0524 and Washington State Water Quality Standards. Data are reported on the following topics: air; Columbia River; sanitary water; surface water; ground water; foodstuffs; wildlife; soil and vegetation; external radiation measurement; portable instrument surveys; and surveillance of waste disposal sites;

Feasibility study for the processing of Hanford Site cesium and strontium isotopic sources in the Hanford Waste Vitrification Plant

International Nuclear Information System (INIS)

Anantatmula, R.P.; Watrous, R.A.; Nelson, J.L.; Perez, J.M.; Peters, R.D.; Peterson, M.E.

1991-09-01

The final environmental impact statement for the disposal of defense-related wastes at the Hanford Site (Final Environmental Impact Statement: Disposal of Hanford Defense High-Level, Transuranic and Tank Wastes [HDW-EIS] [DOE 1987]) states that the preferred alternative for disposal of cesium and strontium wastes at the Hanford Site will be to package and ship these wastes to the commercial high-level waste repository. The Record of Decision for this EIS states that before shipment to a geologic repository, these wastes will be packaged in accordance with repository waste acceptance criteria. However, the high cost per canister for repository disposal and uncertainty about the acceptability of overpacked capsules by the repository suggest that additional alternative means of disposal be considered. Vitrification of the cesium and strontium salts in the Hanford Waste Vitrification Plant (HWVP) has been identified as a possible alternative to overpacking. Subsequently, Westinghouse Hanford Company's (Westinghouse Hanford) Projects Technical Support Office undertook a feasibility study to determine if any significant technical issues preclude the vitrification of the cesium and strontium salts. Based on the information presented in this report, it is considered technically feasible to blend the cesium chloride and strontium fluoride salts with neutralized current acid waste (NCAW) and/or complexant concentrate (CC) waste feedstreams, or to blend the salts with fresh frit and process the waste through the HWVP

The Peroxisomal NAD Carrier from Arabidopsis Imports NAD in Exchange with AMP.

Science.gov (United States)

van Roermund, Carlo W T; Schroers, Martin G; Wiese, Jan; Facchinelli, Fabio; Kurz, Samantha; Wilkinson, Sabrina; Charton, Lennart; Wanders, Ronald J A; Waterham, Hans R; Weber, Andreas P M; Link, Nicole

2016-07-01

Cofactors such as NAD, AMP, and Coenzyme A (CoA) are essential for a diverse set of reactions and pathways in the cell. Specific carrier proteins are required to distribute these cofactors to different cell compartments, including peroxisomes. We previously identified a peroxisomal transport protein in Arabidopsis (Arabidopsis thaliana) called the peroxisomal NAD carrier (PXN). When assayed in vitro, this carrier exhibits versatile transport functions, e.g. catalyzing the import of NAD or CoA, the exchange of NAD/NADH, and the export of CoA. These observations raise the question about the physiological function of PXN in plants. Here, we used Saccharomyces cerevisiae to address this question. First, we confirmed that PXN, when expressed in yeast, is active and targeted to yeast peroxisomes. Secondl, detailed uptake analyses revealed that the CoA transport function of PXN can be excluded under physiological conditions due to its low affinity for this substrate. Third, we expressed PXN in diverse mutant yeast strains and investigated the suppression of the mutant phenotypes. These studies provided strong evidences that PXN was not able to function as a CoA transporter or a redox shuttle by mediating a NAD/NADH exchange, but instead catalyzed the import of NAD into peroxisomes against AMP in intact yeast cells. © 2016 American Society of Plant Biologists. All Rights Reserved.

Hanford whole body counting manual

International Nuclear Information System (INIS)

Palmer, H.E.; Rieksts, G.A.; Lynch, T.P.

1990-06-01

This document describes the Hanford Whole Body Counting Program as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy--Richland Operations Office (DOE-RL) and its Hanford contractors. Program services include providing in vivo measurements of internally deposited radioactivity in Hanford employees (or visitors). Specific chapters of this manual deal with the following subjects: program operational charter, authority, administration, and practices, including interpreting applicable DOE Orders, regulations, and guidance into criteria for in vivo measurement frequency, etc., for the plant-wide whole body counting services; state-of-the-art facilities and equipment used to provide the best in vivo measurement results possible for the approximately 11,000 measurements made annually; procedures for performing the various in vivo measurements at the Whole Body Counter (WBC) and related facilities including whole body counts; operation and maintenance of counting equipment, quality assurance provisions of the program, WBC data processing functions, statistical aspects of in vivo measurements, and whole body counting records and associated guidance documents. 16 refs., 48 figs., 22 tabs

Designation of facility usage categories for Hanford Site facilities

International Nuclear Information System (INIS)

Wodrich, D.; Ellingson, D.; Scott, M.; Schade, A.

1991-01-01

This report summarizes the Hanford Site methodology used to ensure facility compliance with the natural phenomena design criteria set forth in the US Department of Energy orders and guidance. In particular, the Hanford Site approach to designating a suitable facility open-quotes Usage Category,close quotes is presented. The current Hanford Site methodology for Usage Category designation is based on an engineered feature's safety function and on the feature's assigned Safety Class. At the Hanford Site, Safety Class assignments are deterministic in nature and are based on the consequences of failure, without regard to the likelihood of occurrence. The report also proposes a risk-based approach to Usage Category designation, which is being considered for future application at the Hanford Site. To establish a proper Usage Category designation, the safety analysis and engineering design processes must be coupled. This union produces a common understanding of the safety function(s) to be accomplished by the design feature(s) and a sound basis for the assignment of Usage Categories to the appropriate systems, structures, and components

Dynamics of NAD-metabolism: everything but constant.

Science.gov (United States)

Opitz, Christiane A; Heiland, Ines

2015-12-01

NAD, as well as its phosphorylated form, NADP, are best known as electron carriers and co-substrates of various redox reactions. As such they participate in approximately one quarter of all reactions listed in the reaction database KEGG. In metabolic pathway analysis, the total amount of NAD is usually assumed to be constant. That means that changes in the redox state might be considered, but concentration changes of the NAD moiety are usually neglected. However, a growing number of NAD-consuming reactions have been identified, showing that this assumption does not hold true in general. NAD-consuming reactions are common characteristics of NAD(+)-dependent signalling pathways and include mono- and poly-ADP-ribosylation of proteins, NAD(+)-dependent deacetylation by sirtuins and the formation of messenger molecules such as cyclic ADP-ribose (cADPR) and nicotinic acid (NA)-ADP (NAADP). NAD-consuming reactions are thus involved in major signalling and gene regulation pathways such as DNA-repair or regulation of enzymes central in metabolism. All known NAD(+)-dependent signalling processes include the release of nicotinamide (Nam). Thus cellular NAD pools need to be constantly replenished, mostly by recycling Nam to NAD(+). This process is, among others, regulated by the circadian clock, causing complex dynamic changes in NAD concentration. As disturbances in NAD homoeostasis are associated with a large number of diseases ranging from cancer to diabetes, it is important to better understand the dynamics of NAD metabolism to develop efficient pharmacological invention strategies to target this pathway. © 2015 Authors; published by Portland Press Limited.

In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences

Science.gov (United States)

Zhu, Xiao-Hong; Lu, Ming; Lee, Byeong-Yeul; Ugurbil, Kamil; Chen, Wei

2015-01-01

NAD is an essential metabolite that exists in NAD+ or NADH form in all living cells. Despite its critical roles in regulating mitochondrial energy production through the NAD+/NADH redox state and modulating cellular signaling processes through the activity of the NAD+-dependent enzymes, the method for quantifying intracellular NAD contents and redox state is limited to a few in vitro or ex vivo assays, which are not suitable for studying a living brain or organ. Here, we present a magnetic resonance (MR) -based in vivo NAD assay that uses the high-field MR scanner and is capable of noninvasively assessing NAD+ and NADH contents and the NAD+/NADH redox state in intact human brain. The results of this study provide the first insight, to our knowledge, into the cellular NAD concentrations and redox state in the brains of healthy volunteers. Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ. PMID:25730862

Restoring NAD(+) Levels with NAD(+) Intermediates, the Second Law of Thermodynamics and Aging Delay.

Science.gov (United States)

Poljsak, Borut; Milisav, Irina

2018-04-26

The hypothesis regarding the role of increased nicotinamide adenine dinucleotide (NAD+) levels with reference to the fundamental concepts of ageing and entropy is presented. Considering the second law of thermodynamics, NAD+ seems the appropriate candidate for reversing many aging-associated pathologies. NAD+ is presented as an essential compound that enables organisms to stay highly organized and well-maintained, with a lower entropy state.

Master schedule for CY-1979 Hanford environmental surveillance routine program

International Nuclear Information System (INIS)

Blumer, P.J.; Houston, J.R.; Eddy, P.A.

1978-12-01

The current schedule of data collection for the routine environmental surveillance program at the Hanford Site, as conducted by the Environmental Evaluation Section of Battelle, Pacific Northwest Laboratory for the Department of Energy (DOE), is given. Modifications to the schedule are made during the year and special areas of study, usually of short duration, are not scheduled. The environmental surveillance program objectives are to evaluate the levels of radioactive and nonradioactive pollutants in the Hanford environs, and to monitor Hanford operations for compliance with applicable environmental criteria and Washington State Water Quality Standards. Air quality data are obtained in a separate program administered by the Hanford Environmental Health Foundation. The collection schedule for potable water is shown but it is not part of the routine environmental surveillance program. Water quality data for Hanford Site potable water systems are published each year by the Hanford Environmental Health Foundation. The data collected are available in routine reports issued by the Environmental Evaluations staff. Groundwater data and evaluation are reported in the series, ''Radiological Status of the Groundwater Beneath the Hanford Project for...,'' the latest issue being PNL-2624 for CY-1977. Data from locations within the plant boundaries are presented in the annual ''Environmental Status of the Hanford Site for...'' report series, the most recent report being PNL-2677 for 1977. Data from offsite locations are presented in the annual ''Environmental Surveillance at Hanford for...'' series of reports, the latest being PNL-2614 for 1977

Designation of facility usage categories for Hanford Site facilities

International Nuclear Information System (INIS)

Woodrich, D.D.; Ellingson, D.R.; Scott, M.A.; Schade, A.R.

1991-10-01

This report summarizes the Hanford Site methodology used to ensure facility compliance with the natural phenomena design criteria set forth in the US Department of Energy Orders and guidance. The current Hanford Site methodology for Usage Category designation is based on an engineered feature's safety function and on the feature's assigned Safety Class. At the Hanford Site, Safety Class assignments are deterministic in nature and are based on teh consequences of failure, without regard to the likelihood of occurrence. The report also proposes a risk-based approach to Usage Category designation, which is being considered for future application at the Hanford Site. To establish a proper Usage Category designation, the safety analysis and engineering design processes must be coupled. This union produces a common understanding of the safety function(s) to be accomplished by the design feature(s) and a sound basis for the assignment of Usage Categories to the appropriate systems, structures, and components. 4 refs., 9 figs., 1 tab

Hanford site transuranic waste certification plan

International Nuclear Information System (INIS)

GREAGER, T.M.

1999-01-01

As a generator of transuranic (TRU) and TRU mixed waste destined for disposal at the Waste Isolation Pilot Plant (WIPP), the Hanford Site must ensure that its TRU waste meets the requirements of U.S. Department of Energy (DOE) Order 5820.2A, ''Radioactive Waste Management, and the Waste Acceptance Criteria for the Waste Isolation Pilot Plant' (DOE 1996d) (WIPP WAC). The WIPP WAC establishes the specific physical, chemical, radiological, and packaging criteria for acceptance of defense TRU waste shipments at WIPP. The WIPP WAC also requires that participating DOE TRU waste generator/treatment/storage sites produce site-specific documents, including a certification plan, that describe their management of TRU waste and TRU waste shipments before transferring waste to WIPP. The Hanford Site must also ensure that its TRU waste destined for disposal at WIPP meets requirements for transport in the Transuranic Package Transporter41 (TRUPACT-11). The U.S. Nuclear Regulatory Commission (NRC) establishes the TRUPACT-I1 requirements in the ''Safety Analysis Report for the TRUPACT-II Shipping Package'' (NRC 1997) (TRUPACT-I1 SARP)

Exploring the therapeutic space around NAD(+)

NARCIS (Netherlands)

Houtkooper, Riekelt H.; Auwerx, Johan

2012-01-01

NAD(+) is a central metabolite in the cell. Changes in NAD(+) abundance and the activity of NAD(+)-dependent enzymes, such as the sirtuins, are at the core of metabolic/mitochondrial diseases, such as obesity and diabetes, and of cancer and neurodegeneration. Here, we discuss how maintaining or

Exploring NAD+ metabolism in host-pathogen interactions.

Science.gov (United States)

Mesquita, Inês; Varela, Patrícia; Belinha, Ana; Gaifem, Joana; Laforge, Mireille; Vergnes, Baptiste; Estaquier, Jérôme; Silvestre, Ricardo

2016-03-01

Nicotinamide adenine dinucleotide (NAD(+)) is a vital molecule found in all living cells. NAD(+) intracellular levels are dictated by its synthesis, using the de novo and/or salvage pathway, and through its catabolic use as co-enzyme or co-substrate. The regulation of NAD(+) metabolism has proven to be an adequate drug target for several diseases, including cancer, neurodegenerative or inflammatory diseases. Increasing interest has been given to NAD(+) metabolism during innate and adaptive immune responses suggesting that its modulation could also be relevant during host-pathogen interactions. While the maintenance of NAD(+) homeostatic levels assures an adequate environment for host cell survival and proliferation, fluctuations in NAD(+) or biosynthetic precursors bioavailability have been described during host-pathogen interactions, which will interfere with pathogen persistence or clearance. Here, we review the double-edged sword of NAD(+) metabolism during host-pathogen interactions emphasizing its potential for treatment of infectious diseases.

Nrt1 and Tna1-independent export of NAD+ precursor vitamins promotes NAD+ homeostasis and allows engineering of vitamin production.

Directory of Open Access Journals (Sweden)

Peter Belenky

2011-05-01

Full Text Available NAD(+ is both a co-enzyme for hydride transfer enzymes and a substrate of sirtuins and other NAD(+ consuming enzymes. NAD(+ biosynthesis is required for two different regimens that extend lifespan in yeast. NAD(+ is synthesized from tryptophan and the three vitamin precursors of NAD(+: nicotinic acid, nicotinamide and nicotinamide riboside. Supplementation of yeast cells with NAD(+ precursors increases intracellular NAD(+ levels and extends replicative lifespan. Here we show that both nicotinamide riboside and nicotinic acid are not only vitamins but are also exported metabolites. We found that the deletion of the nicotinamide riboside transporter, Nrt1, leads to increased export of nicotinamide riboside. This discovery was exploited to engineer a strain to produce high levels of extracellular nicotinamide riboside, which was recovered in purified form. We further demonstrate that extracellular nicotinamide is readily converted to extracellular nicotinic acid in a manner that requires intracellular nicotinamidase activity. Like nicotinamide riboside, export of nicotinic acid is elevated by the deletion of the nicotinic acid transporter, Tna1. The data indicate that NAD(+ metabolism has a critical extracellular element in the yeast system and suggest that cells regulate intracellular NAD(+ metabolism by balancing import and export of NAD(+ precursor vitamins.

Environmental Restoration Program quality system requirements for the Hanford Site

International Nuclear Information System (INIS)

Cote, R.F.

1993-11-01

This document defines the quality system requirements for the US Department of Energy, Richland Operations Office, Environmental Restoration Program at the Hanford Site. The Quality System Requirements (OSR) for the Hanford Site integrates quality assurance requirements from the US Department of Energy Orders, the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement), and applicable industry standards into a single source document for the development of quality systems applicable to the Environmental Restoration Program activities. This document, based on fifteen criteria and divided intro three parts, provides user organizations with the flexibility to incorporate only those criteria and parts applicable to their specific scopes of work. The requirements of this document shall be applied to activities that affect quality based on a graded approach that takes into consideration the risk inherent in, as well as the importance of, specific items, services, and activities in terms of meeting ER Program objectives and customer expectations. The individual quality systems developed in accordance with this document are intended to provide an integrated management control system that assures the conduct of ER Program activities in a manner that protects human health and the environment

Decision process for Hanford sitewide groundwater remediation

International Nuclear Information System (INIS)

Chiaramonte, G.R.

1996-06-01

This document describes a decision process for planning future investigations and remediating contaminated groundwater at the Hanford Site in Richland, Washington. This decision process details the following: identifies key decisions and activities; defines the criteria used in making each decision; and defines the logic that links the decisions and the activities in a stepwise manner

The dynamic regulation of NAD metabolism in mitochondria

Science.gov (United States)

Stein, Liana Roberts; Imai, Shin-ichiro

2012-01-01

Mitochondria are intracellular powerhouses that produce ATP and carry out diverse functions for cellular energy metabolism. While the maintenance of an optimal NAD/NADH ratio is essential for mitochondrial function, it has recently become apparent that the maintenance of the mitochondrial NAD pool also has critical importance. The biosynthesis, transport, and catabolism of NAD and its key intermediates play an important role in the regulation of NAD-consuming mediators, such as sirtuins, poly-ADP-ribose polymerases, and CD38/157 ectoenzymes, in intra- and extracellular compartments. Mitochondrial NAD biosynthesis is also modulated in response to nutritional and environmental stimuli. In this article, we discuss this dynamic regulation of NAD metabolism in mitochondria to shed light on the intimate connection between NAD and mitochondrial function. PMID:22819213

NAD+ in Aging: Molecular Mechanisms and Translational Implications.

Science.gov (United States)

Fang, Evandro F; Lautrup, Sofie; Hou, Yujun; Demarest, Tyler G; Croteau, Deborah L; Mattson, Mark P; Bohr, Vilhelm A

2017-10-01

The coenzyme NAD + is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD + levels is important for cells with high energy demands and for proficient neuronal function. NAD + depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD + decrements occur in various tissues during aging, and that physiological and pharmacological interventions bolstering cellular NAD + levels might retard aspects of aging and forestall some age-related diseases. Here, we discuss aspects of NAD + biosynthesis, together with putative mechanisms of NAD + action against aging, including recent preclinical and clinical trials. Published by Elsevier Ltd.

Environmental Restoration Disposal Facility Waste Acceptance Criteria

International Nuclear Information System (INIS)

Dronen, V.R.

1998-06-01

The Hanford Site is operated by the U. S. Department of Energy (DOE) with a primary mission of environmental cleanup and restoration. The Environmental Restoration Disposal Facility (ERDF) is an integral part of the DOE environmental restoration effort at the Hanford Site. The purpose of this document is to establish the ERDF waste acceptance criteria for disposal of materials resulting from Hanford Site cleanup activities. Definition of and compliance with the requirements of this document will enable implementation of appropriate measures to protect human health and the environment, ensure the integrity of the ERDF liner system, facilitate efficient use of the available space in the ERDF, and comply with applicable environmental regulations and DOE orders. To serve this purpose, the document defines responsibilities, identifies the waste acceptance process, and provides the primary acceptance criteria and regulatory citations to guide ERDF users. The information contained in this document is not intended to repeat or summarize the contents of all applicable regulations

Hanford Internal Dosimetry Project manual. Revision 1

International Nuclear Information System (INIS)

Carbaugh, E.H.; Bihl, D.E.; MacLellan, J.A.; Long, M.P.

1994-07-01

This document describes the Hanford Internal Dosimetry Project, as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy and its Hanford contractors. Project services include administrating the bioassay monitoring program, evaluating and documenting assessment of potential intakes and internal dose, ensuring that analytical laboratories conform to requirements, selecting and applying appropriate models and procedures for evaluating radionuclide deposition and the resulting dose, and technically guiding and supporting Hanford contractors in matters regarding internal dosimetry. Specific chapters deal with the following subjects: practices of the project, including interpretation of applicable DOE Orders, regulations, and guidance into criteria for assessment, documentation, and reporting of doses; assessment of internal dose, including summary explanations of when and how assessments are performed; recording and reporting practices for internal dose; selection of workers for bioassay monitoring and establishment of type and frequency of bioassay measurements; capability and scheduling of bioassay monitoring services; recommended dosimetry response to potential internal exposure incidents; quality control and quality assurance provisions of the program

Hanford Internal Dosimetry Project manual. Revision 1

Energy Technology Data Exchange (ETDEWEB)

Carbaugh, E.H.; Bihl, D.E.; MacLellan, J.A.; Long, M.P.

1994-07-01

This document describes the Hanford Internal Dosimetry Project, as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy and its Hanford contractors. Project services include administrating the bioassay monitoring program, evaluating and documenting assessment of potential intakes and internal dose, ensuring that analytical laboratories conform to requirements, selecting and applying appropriate models and procedures for evaluating radionuclide deposition and the resulting dose, and technically guiding and supporting Hanford contractors in matters regarding internal dosimetry. Specific chapters deal with the following subjects: practices of the project, including interpretation of applicable DOE Orders, regulations, and guidance into criteria for assessment, documentation, and reporting of doses; assessment of internal dose, including summary explanations of when and how assessments are performed; recording and reporting practices for internal dose; selection of workers for bioassay monitoring and establishment of type and frequency of bioassay measurements; capability and scheduling of bioassay monitoring services; recommended dosimetry response to potential internal exposure incidents; quality control and quality assurance provisions of the program.

NAD+ salvage pathway in cancer metabolism and therapy.

Science.gov (United States)

Kennedy, Barry E; Sharif, Tanveer; Martell, Emma; Dai, Cathleen; Kim, Youra; Lee, Patrick W K; Gujar, Shashi A

2016-12-01

Nicotinamide adenine dinucleotide (NAD + ) is an essential coenzyme for various physiological processes including energy metabolism, DNA repair, cell growth, and cell death. Many of these pathways are typically dysregulated in cancer cells, making NAD + an intriguing target for cancer therapeutics. NAD + is mainly synthesized by the NAD + salvage pathway in cancer cells, and not surprisingly, the pharmacological targeting of the NAD + salvage pathway causes cancer cell cytotoxicity in vitro and in vivo. Several studies have described the precise consequences of NAD + depletion on cancer biology, and have demonstrated that NAD+ depletion results in depletion of energy levels through lowered rates of glycolysis, reduced citric acid cycle activity, and decreased oxidative phosphorylation. Additionally, depletion of NAD + causes sensitization of cancer cells to oxidative damage by disruption of the anti-oxidant defense system, decreased cell proliferation, and initiation of cell death through manipulation of cell signaling pathways (e.g., SIRT1 and p53). Recently, studies have explored the effect of well-known cancer therapeutics in combination with pharmacological depletion of NAD + levels, and found in many cases a synergistic effect on cancer cell cytotoxicity. In this context, we will discuss the effects of NAD + salvage pathway inhibition on cancer cell biology and provide insight on this pathway as a novel anti-cancer therapeutic target. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fluor Hanford Project Focused Progress at Hanford

International Nuclear Information System (INIS)

HANSON, R.D.

2000-01-01

Fluor Hanford is making significant progress in accelerating cleanup at the Hanford site. This progress consistently aligns with a new strategic vision established by the U.S. Department of Energy's Richland Operations Office (RL)

NAD+ : A key metabolic regulator with great therapeutic potential.

Science.gov (United States)

Sultani, G; Samsudeen, A F; Osborne, B; Turner, N

2017-10-01

Nicotinamide adenine dinucleotide (NAD + ) is a ubiquitous metabolite that serves an essential role in the catabolism of nutrients. Recently, there has been a surge of interest in NAD + biology, with the recognition that NAD + influences many biological processes beyond metabolism, including transcription, signalling and cell survival. There are a multitude of pathways involved in the synthesis and breakdown of NAD + , and alterations in NAD + homeostasis have emerged as a common feature of a range of disease states. Here, we provide an overview of NAD + metabolism and summarise progress on the development of NAD + -related therapeutics. © 2017 British Society for Neuroendocrinology.

Identification of NAD interacting residues in proteins

Directory of Open Access Journals (Sweden)

Raghava Gajendra PS

2010-03-01

Full Text Available Abstract Background Small molecular cofactors or ligands play a crucial role in the proper functioning of cells. Accurate annotation of their target proteins and binding sites is required for the complete understanding of reaction mechanisms. Nicotinamide adenine dinucleotide (NAD+ or NAD is one of the most commonly used organic cofactors in living cells, which plays a critical role in cellular metabolism, storage and regulatory processes. In the past, several NAD binding proteins (NADBP have been reported in the literature, which are responsible for a wide-range of activities in the cell. Attempts have been made to derive a rule for the binding of NAD+ to its target proteins. However, so far an efficient model could not be derived due to the time consuming process of structure determination, and limitations of similarity based approaches. Thus a sequence and non-similarity based method is needed to characterize the NAD binding sites to help in the annotation. In this study attempts have been made to predict NAD binding proteins and their interacting residues (NIRs from amino acid sequence using bioinformatics tools. Results We extracted 1556 proteins chains from 555 NAD binding proteins whose structure is available in Protein Data Bank. Then we removed all redundant protein chains and finally obtained 195 non-redundant NAD binding protein chains, where no two chains have more than 40% sequence identity. In this study all models were developed and evaluated using five-fold cross validation technique on the above dataset of 195 NAD binding proteins. While certain type of residues are preferred (e.g. Gly, Tyr, Thr, His in NAD interaction, residues like Ala, Glu, Leu, Lys are not preferred. A support vector machine (SVM based method has been developed using various window lengths of amino acid sequence for predicting NAD interacting residues and obtained maximum Matthew's correlation coefficient (MCC 0.47 with accuracy 74.13% at window length 17

Modulating NAD+ metabolism, from bench to bedside.

Science.gov (United States)

Katsyuba, Elena; Auwerx, Johan

2017-09-15

Discovered in the beginning of the 20 th century, nicotinamide adenine dinucleotide (NAD + ) has evolved from a simple oxidoreductase cofactor to being an essential cosubstrate for a wide range of regulatory proteins that include the sirtuin family of NAD + -dependent protein deacylases, widely recognized regulators of metabolic function and longevity. Altered NAD + metabolism is associated with aging and many pathological conditions, such as metabolic diseases and disorders of the muscular and neuronal systems. Conversely, increased NAD + levels have shown to be beneficial in a broad spectrum of diseases. Here, we review the fundamental aspects of NAD + biochemistry and metabolism and discuss how boosting NAD + content can help ameliorate mitochondrial homeostasis and as such improve healthspan and lifespan. © 2017 The Authors.

The human NAD metabolome: Functions, metabolism and compartmentalization

Science.gov (United States)

Nikiforov, Andrey; Kulikova, Veronika; Ziegler, Mathias

2015-01-01

Abstract The metabolism of NAD has emerged as a key regulator of cellular and organismal homeostasis. Being a major component of both bioenergetic and signaling pathways, the molecule is ideally suited to regulate metabolism and major cellular events. In humans, NAD is synthesized from vitamin B3 precursors, most prominently from nicotinamide, which is the degradation product of all NAD-dependent signaling reactions. The scope of NAD-mediated regulatory processes is wide including enzyme regulation, control of gene expression and health span, DNA repair, cell cycle regulation and calcium signaling. In these processes, nicotinamide is cleaved from NAD+ and the remaining ADP-ribosyl moiety used to modify proteins (deacetylation by sirtuins or ADP-ribosylation) or to generate calcium-mobilizing agents such as cyclic ADP-ribose. This review will also emphasize the role of the intermediates in the NAD metabolome, their intra- and extra-cellular conversions and potential contributions to subcellular compartmentalization of NAD pools. PMID:25837229

Plans for Managing Hanford Remote Handled Transuranic (TRU) Waste

International Nuclear Information System (INIS)

MCKENNEY, D.E.

2001-01-01

The current Hanford Site baseline and life-cycle waste forecast predicts that approximately 1,000 cubic meters of remote-handled transuranic (RH-TRU) waste will be generated by waste management and environmental restoration activities at Hanford. These 1,000 cubic meters, comprised of both transuranic and mixed transuranic (TRUM) waste, represent a significant portion of the total estimated inventory of RH-TRU to be disposed of at the Waste Isolation Pilot Plant (WIPP). A systems engineering approach is being followed to develop a disposition plan for each RH-TRU/TRUM waste stream at Hanford. A number of significant decision-making efforts are underway to develop and finalize these disposition plans, including: development and approval of a RH-TRU/TRUM Waste Project Management Plan, revision of the Hanford Waste Management Strategic Plan, the Hanford Site Options Study (''Vision 2012''), the Canyon Disposal Initiative Record-of-Decision, and the Hanford Site Solid (Radioactive and Hazardous) Waste Program Environmental Impact Statement (SW-EIS). Disposition plans may include variations of several options, including (1) sending most RH-TRU/TRUM wastes to WIPP, (2) deferrals of waste disposal decisions in the interest of both efficiency and integration with other planned decision dates and (3) disposition of some materials in place consistent with Department of Energy Orders and the regulations in the interest of safety, risk minimization, and cost. Although finalization of disposition paths must await completion of the aforementioned decision documents, significant activities in support of RH-TRU/TRUM waste disposition are proceeding, including Hanford participation in development of the RH TRU WIPP waste acceptance criteria, preparation of T Plant for interim storage of spent nuclear fuel sludge, sharing of technology information and development activities in cooperation with the Mixed Waste Focus Area, RH-TRU technology demonstrations and deployments, and

Pathways and Subcellular Compartmentation of NAD Biosynthesis in Human Cells

Science.gov (United States)

Nikiforov, Andrey; Dölle, Christian; Niere, Marc; Ziegler, Mathias

2011-01-01

NAD is a vital redox carrier, and its degradation is a key element of important regulatory pathways. NAD-mediated functions are compartmentalized and have to be fueled by specific biosynthetic routes. However, little is known about the different pathways, their subcellular distribution, and regulation in human cells. In particular, the route(s) to generate mitochondrial NAD, the largest subcellular pool, is still unknown. To visualize organellar NAD changes in cells, we targeted poly(ADP-ribose) polymerase activity into the mitochondrial matrix. This activity synthesized immunodetectable poly(ADP-ribose) depending on mitochondrial NAD availability. Based on this novel detector system, detailed subcellular enzyme localizations, and pharmacological inhibitors, we identified extracellular NAD precursors, their cytosolic conversions, and the pathway of mitochondrial NAD generation. Our results demonstrate that, besides nicotinamide and nicotinic acid, only the corresponding nucleosides readily enter the cells. Nucleotides (e.g. NAD and NMN) undergo extracellular degradation resulting in the formation of permeable precursors. These precursors can all be converted to cytosolic and mitochondrial NAD. For mitochondrial NAD synthesis, precursors are converted to NMN in the cytosol. When taken up into the organelles, NMN (together with ATP) serves as substrate of NMNAT3 to form NAD. NMNAT3 was conclusively localized to the mitochondrial matrix and is the only known enzyme of NAD synthesis residing within these organelles. We thus present a comprehensive dissection of mammalian NAD biosynthesis, the groundwork to understand regulation of NAD-mediated processes, and the organismal homeostasis of this fundamental molecule. PMID:21504897

Hanford Site air operating permit application

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-05-01

The Clean Air Act Amendments of 1990, which amended the Federal Clean Air Act of 1977, required that the US Environmental Protection Agency develop a national Air Operating Permit Program, which in turn would require each state to develop an Air Operating Permit Program to identify all sources of ``regulated`` pollutants. Regulated pollutants include ``criteria`` pollutants (oxides of nitrogen, sulfur oxides, total suspended particulates, carbon monoxide, particulate matter greater than 10 micron, lead) plus 189 other ``Hazardous`` Air Pollutants. The Hanford Site, owned by the US Government and operated by the US Department of Energy, Richland Operations Office, is located in southcentral Washington State and covers 560 square miles of semi-arid shrub and grasslands located just north of the confluence of the Snake and Yakima Rivers with the Columbia River. This land, with restricted public access, provides a buffer for the smaller areas historically used for the production of nuclear materials, waste storage, and waste disposal. About 6 percent of the land area has been disturbed and is actively used. The Hanford Site Air Operating Permit Application consists of more than 1,100 sources and in excess of 300 emission points. Before January 1995, the maintenance and operations contractor and the environmental restoration contractor for the US Department of Energy completed an air emission inventory on the Hanford Site. The inventory has been entered into a database so that the sources and emission points can be tracked and updated information readily can be retrieved. The Hanford Site Air Operating Permit Application contains information current as of April 19, 1995.

Hanford Site air operating permit application

International Nuclear Information System (INIS)

1995-05-01

The Clean Air Act Amendments of 1990, which amended the Federal Clean Air Act of 1977, required that the US Environmental Protection Agency develop a national Air Operating Permit Program, which in turn would require each state to develop an Air Operating Permit Program to identify all sources of ''regulated'' pollutants. Regulated pollutants include ''criteria'' pollutants (oxides of nitrogen, sulfur oxides, total suspended particulates, carbon monoxide, particulate matter greater than 10 micron, lead) plus 189 other ''Hazardous'' Air Pollutants. The Hanford Site, owned by the US Government and operated by the US Department of Energy, Richland Operations Office, is located in southcentral Washington State and covers 560 square miles of semi-arid shrub and grasslands located just north of the confluence of the Snake and Yakima Rivers with the Columbia River. This land, with restricted public access, provides a buffer for the smaller areas historically used for the production of nuclear materials, waste storage, and waste disposal. About 6 percent of the land area has been disturbed and is actively used. The Hanford Site Air Operating Permit Application consists of more than 1,100 sources and in excess of 300 emission points. Before January 1995, the maintenance and operations contractor and the environmental restoration contractor for the US Department of Energy completed an air emission inventory on the Hanford Site. The inventory has been entered into a database so that the sources and emission points can be tracked and updated information readily can be retrieved. The Hanford Site Air Operating Permit Application contains information current as of April 19, 1995

The NAD+/PARP1/SIRT1 Axis in Aging.

Science.gov (United States)

Mendelsohn, Andrew R; Larrick, James W

2017-06-01

NAD+ levels decline with age in diverse animals from Caenorhabditis elegans to mice. Raising NAD+ levels by dietary supplementation with NAD+ precursors, nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), improves mitochondrial function and muscle and neural and melanocyte stem cell function in mice, as well as increases murine life span. Decreased NAD+ levels with age reduce SIRT1 function and reduce the mitochondrial unfolded protein response, which can be overcome by NR supplementation. Decreased NAD+ levels cause NAD+-binding protein DBC1 to form a complex with PARP1, inhibiting poly(adenosine diphosphate-ribose) polymerase (PARP) catalytic activity. Old mice have increased amounts of DBC1-PARP1 complexes, lower PARP activity, increased DNA damage, and reduced nonhomologous end joining and homologous recombination repair. DBC1-PARP1 complexes in old mice can be broken by increasing NAD+ levels through treatment with NMN, reducing DNA damage and restoring PARP activity to youthful levels. The mechanism of declining NAD+ levels and its fundamental importance to aging are yet to be elucidated. There is a correlation of PARP activity with mammalian life span that suggests that NAD+/SIRT1/PARP1 may be more significant than the modest effects on life span observed for NR supplementation in old mice. The NAD+/PARP1/SIRT1 axis may link NAD+ levels and DNA damage with the apparent epigenomic DNA methylation clocks that have been described.

Westinghouse Hanford Company plan for certifying newly generated contact-handled transuranic waste for emplacement in the Waste Isolation Pilot Plant

International Nuclear Information System (INIS)

Lipinski, R.M.; Sheehan, J.S.

1992-07-01

Westinghouse Hanford Company (Westinghouse Hanford) currently manages an interim storage site for Westinghouse Hanford and non-Westinghouse Hanford-generated transuranic (TRU) waste and operates TRU waste generating facilities within the Hanford Site in Washington State. Approval has been received from the Waste Acceptance Criteria Certification Committee (WACCC) and Westinghouse Hanford TRU waste generating facilities to certify newly generated contact-handled TRU (CH-TRU) solid waste to meet the Waste Acceptance Criteria (WAC). This document describes the plan for certifying newly generated CH-TRU solid waste to meet the WAC requirements for storage at the Waste Isolation Pilot Plant (WIPP) site. Attached to this document are facility-specific certification plans for the Westinghouse Hanford TRU waste generators that have received WACCC approval. The certification plans describe operations that generate CH-TRU solid waste and the specific procedures by which these wastes will be certified and segregated from uncertified wastes at the generating facilities. All newly generated CH-TRU solid waste is being transferred to the Transuranic Storage and Assay Facility (TRUSAF) and/or a controlled storage facility. These facilities will store the waste until the certified TRU waste can be sent to the WIPP site and the non-certified TRU waste can be sent to the Waste Receiving and Processing Facility. All non-certifiable TRU waste will be segregated and clearly identified

NAD Acts as an Integral Regulator of Multiple Defense Layers.

Science.gov (United States)

Pétriacq, Pierre; Ton, Jurriaan; Patrit, Oriane; Tcherkez, Guillaume; Gakière, Bertrand

2016-11-01

Pyridine nucleotides, such as NAD, are crucial redox carriers and have emerged as important signaling molecules in stress responses. Previously, we have demonstrated in Arabidopsis (Arabidopsis thaliana) that the inducible NAD-overproducing nadC lines are more resistant to an avirulent strain of Pseudomonas syringae pv tomato (Pst-AvrRpm1), which was associated with salicylic acid-dependent defense. Here, we have further characterized the NAD-dependent immune response in Arabidopsis. Quinolinate-induced stimulation of intracellular NAD in transgenic nadC plants enhanced resistance against a diverse range of (a)virulent pathogens, including Pst-AvrRpt2, Dickeya dadantii, and Botrytis cinerea Characterization of the redox status demonstrated that elevated NAD levels induce reactive oxygen species (ROS) production and the expression of redox marker genes of the cytosol and mitochondrion. Using pharmacological and reverse genetics approaches, we show that NAD-induced ROS production functions independently of NADPH oxidase activity and light metabolism but depends on mitochondrial respiration, which was increased at higher NAD. We further demonstrate that NAD primes pathogen-induced callose deposition and cell death. Mass spectrometry analysis reveals that NAD simultaneously induces different defense hormones and that the NAD-induced metabolic profiles are similar to those of defense-expressing plants after treatment with pathogen-associated molecular patterns. We thus conclude that NAD triggers metabolic profiles rather similar to that of pathogen-associated molecular patterns and discuss how signaling cross talk between defense hormones, ROS, and NAD explains the observed resistance to pathogens. © 2016 American Society of Plant Biologists. All Rights Reserved.

In vivo (31) P MRS assessment of intracellular NAD metabolites and NAD(+) /NADH redox state in human brain at 4 T.

Science.gov (United States)

Lu, Ming; Zhu, Xiao-Hong; Chen, Wei

2016-07-01

NAD(+) and NADH play key roles in cellular respiration. Intracellular redox state defined by the NAD(+) /NADH ratio (RX) reflects the cellular metabolic and physiopathological status. By taking advantage of high/ultrahigh magnetic field strengths, we have recently established a novel in vivo (31) P MRS-based NAD assay for noninvasive and quantitative measurements of intracellular NAD concentrations and redox state in animal and human brains at 16.4 T, 9.4 T and 7 T. To explore its potential for clinical application, in this study we investigated the feasibility of assessing the NAD metabolism and redox state in human brain at a lower field of 4 T by incorporating the (1) H-decoupling technique with the in vivo (31) P NAD assay. The use of (1) H decoupling significantly narrowed the linewidths of NAD and α-ATP resonances, resulting in higher sensitivity and better spectral resolution as compared with the (1) H-coupled (31) P spectrum. These improvements made it possible to reliably quantify cerebral NAD concentrations and RX, consistent with previously reported results obtained from similar age human subjects at 7 T. In summary, this work demonstrates the capability and utility of the (1) H-decoupled (31) P MRS-based NAD assay at lower field strength; thus, it opens new opportunities for studying intracellular NAD metabolism and redox state in human brain at clinical settings. This conclusion is supported by the simulation results, indicating that similar performance and reliability as observed at 4T can be achieved at 3 T with the same signal-to-noise ratio. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Documentation of Hanford Site independent review of the Hanford Waste Vitrification Plant Preliminary Safety Analysis Report

International Nuclear Information System (INIS)

Herborn, D.I.

1993-11-01

Westinghouse Hanford Company (WHC) is the Integrating Contractor for the Hanford Waste Vitrification Plant (HWVP) Project, and as such is responsible for preparation of the HWVP Preliminary Safety Analysis Report (PSAR). The HWVP PSAR was prepared pursuant to the requirements for safety analyses contained in US Department of Energy (DOE) Orders 4700.1, Project Management System (DOE 1987); 5480.5, Safety of Nuclear Facilities (DOE 1986a); 5481.lB, Safety Analysis and Review System (DOE 1986b) which was superseded by DOE order 5480-23, Nuclear Safety Analysis Reports, for nuclear facilities effective April 30, 1992 (DOE 1992); and 6430.lA, General Design Criteria (DOE 1989). The WHC procedures that, in large part, implement these DOE requirements are contained in WHC-CM-4-46, Nonreactor Facility Safety Analysis Manual. This manual describes the overall WHC safety analysis process in terms of requirements for safety analyses, responsibilities of the various contributing organizations, and required reviews and approvals

TARGETED, LCMS-BASED METABOLOMICS FOR QUANTITATIVE MEASUREMENT OF NAD+ METABOLITES

Directory of Open Access Journals (Sweden)

Samuel AJ Trammell

2013-01-01

Full Text Available Nicotinamide adenine dinucleotide (NAD+ is a coenzyme for hydride transfer reactions and a substrate for sirtuins and other NAD+-consuming enzymes. The abundance of NAD+, NAD+ biosynthetic intermediates, and related nucleotides reflects the metabolic state of cells and tissues. High performance liquid chromatography (HPLC followed by ultraviolet-visible (UV-Vis spectroscopic analysis of NAD+ metabolites does not offer the specificity and sensitivity necessary for robust quantification of complex samples. Thus, we developed a targeted, quantitative assay of the NAD+ metabolome with the use of HPLC coupled to mass spectrometry. Here we discuss NAD+ metabolism as well as the technical challenges required for reliable quantification of the NAD+ metabolites. The new method incorporates new separations and improves upon a previously published method that suffered from the problem of ionization suppression for particular compounds.

Final report of fugitive and diffuse emissions evaluations at the Hanford Site, CY 1994

International Nuclear Information System (INIS)

Gleckler, B.P.; Schmidt, J.W.

1995-01-01

The objective of this study was to evaluate several of Hanford's major diffuse emission sources and evaluate the effectiveness of monitoring these sources individually versus collectively. The results from this evaluation may also be utilized to demonstrate Westinghouse's compliance status with the applicable air emissions regulations and determine if additional studies and/or evaluations are necessary. Air sampling results from four waste handling and storage facilities were collected for a one week period and analyzed. The following is a list of the selected sampling sites: Plutonium Finishing Plant; 241-BY Tank Farm; 1301-N Trench; 300 Area Trenches and North Ponds. These sites were chosen as being representative of most of the Hanford waste sites, which are known to be diffuse emission sites. The sites were evaluated on the following criteria: physical size, surface contamination levels, geology, vegetation density, surface cover, potential for occupational exposure, and potential for public exposure. The selected sites vary greatly with the selection criteria parameters, and as a result should provide representative data for most of Hanford's waste sites

Effect of X-rays and u.v.-light on the levels of NAD(P), NAD(P)H and hydroxyproline in Pinus silvestris pollen

International Nuclear Information System (INIS)

Zelles, L.

1978-01-01

Pollen grains of Pinus Silvestris were irradiated with stimulating and inhibiting doses of X-rays and u.v.-light and the levels of NAD(P), NAD(P)H and hydroxyproline determined during tube growth. Pollen grains irradiated with stimulating doses of X-rays and u.v.-light developed longer tubes, while grains irradiated with inhibiting doses of X-rays and u.v.-light developed shorter tubes than the unirradiated controls. After 32 hr of incubation, the levels of NAD(P), NAD(P)H and hydroxyproline were at their lowest compared with unirradiated pollen. In samples with stimulating doses of irradiation NAD(P) reached its maximum earlier than in samples with inhibiting irradiation. The ratio between the concentrations of NAD(P) and NAD(P)H in the irradiated samples was higher than in the unirradiated control. The hydroxyproline content was higher in irradiated than in unirradiated pollen. (author)

Neuronal death induced by misfolded prion protein is due to NAD+ depletion and can be relieved in vitro and in vivo by NAD+ replenishment

Science.gov (United States)

Zhou, Minghai; Ottenberg, Gregory; Sferrazza, Gian Franco; Hubbs, Christopher; Fallahi, Mohammad; Rumbaugh, Gavin; Brantley, Alicia F.

2015-01-01

The mechanisms of neuronal death in protein misfolding neurodegenerative diseases such as Alzheimer’s, Parkinson’s and prion diseases are poorly understood. We used a highly toxic misfolded prion protein (TPrP) model to understand neurotoxicity induced by prion protein misfolding. We show that abnormal autophagy activation and neuronal demise is due to severe, neuron-specific, nicotinamide adenine dinucleotide (NAD+) depletion. Toxic prion protein-exposed neuronal cells exhibit dramatic reductions of intracellular NAD+ followed by decreased ATP production, and are completely rescued by treatment with NAD+ or its precursor nicotinamide because of restoration of physiological NAD+ levels. Toxic prion protein-induced NAD+ depletion results from PARP1-independent excessive protein ADP-ribosylations. In vivo, toxic prion protein-induced degeneration of hippocampal neurons is prevented dose-dependently by intracerebral injection of NAD+. Intranasal NAD+ treatment of prion-infected sick mice significantly improves activity and delays motor impairment. Our study reveals NAD+ starvation as a novel mechanism of autophagy activation and neurodegeneration induced by a misfolded amyloidogenic protein. We propose the development of NAD+ replenishment strategies for neuroprotection in prion diseases and possibly other protein misfolding neurodegenerative diseases. PMID:25678560

Master schedule for CY-1981 Hanford environmental surveillance routine program

International Nuclear Information System (INIS)

Blumer, P.J.; Sula, M.J.; Eddy, P.A.

1980-12-01

The current schedule of data collection for the routine environmental surveillance program at the Hanford Site is provided. Questions about specific entries should be referred to the authors since modifications to the schedule are made during the year and special areas of study, usually of short duration, are not scheduled. The environmental surveillance program objectives are to evaluate the levels of radioactive and nonradioactive pollutants in the Hanford environs, as required in Manual Chapter 0513, and to monitor Hanford operations for compliance with applicable environmental criteria given in Manual Chapter 0524 and Washington State Water Quality Standards. Air quality data obtained in a separate program are also reported. The collection schedule for potable water is shown but it is not part of the routine environmental surveillance program. Schedules are presented for the following subjects: air, Columbia River, sanitary water, surface water, ground water, foodstuffs, wildlife, soil and vegetation, external radiation measurement, portable instrument surveys, and surveillance of waste disposal sites

Hanford grout disposal program - an environmentally sound alternative

International Nuclear Information System (INIS)

Bergman, T.B.; Allison, J.M.

1987-01-01

The Hanford Grout Disposal Program (HGDP) is a comprehensive, integrated program to develop technology and facilities for the disposal of ∼ 3.0 x 10 5 m 3 (80 million gal) of the low-level fraction of liquid radioactive tank wastes at the Hanford site in southeastern Washington state. Environmentally sound disposal via long-term protection of the public and the environment is the principal goal of the HGDP. To accomplish this goal, several criteria have been established that guide technology and facility development activities. The key criteria are discussed. To meet the challenges posed by disposal of these wastes, the HGDP is developing a waste form using grout-forming materials, such as blast furnace slag, fly ash, clays, and Portland cement for solidification and immobilization of both the radioactive and hazardous chemical constituents. In addition to development of a final waste form, the HGDP is also developing a unique disposal system to assure long-term protection of the public and the environment. Disposal of a low-level nonhazardous waste will be initiated, as a demonstration of the disposal system concept, in June 1988. Disposal of higher activity hazardous wastes is scheduled to begin in October 1989

Hanford External Dosimetry Program

International Nuclear Information System (INIS)

Fix, J.J.

1990-10-01

This document describes the Hanford External Dosimetry Program as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy (DOE) and its Hanford contractors. Program services include administrating the Hanford personnel dosimeter processing program and ensuring that the related dosimeter data accurately reflect occupational dose received by Hanford personnel or visitors. Specific chapters of this report deal with the following subjects: personnel dosimetry organizations at Hanford and the associated DOE and contractor exposure guidelines; types, characteristics, and procurement of personnel dosimeters used at Hanford; personnel dosimeter identification, acceptance testing, accountability, and exchange; dosimeter processing and data recording practices; standard sources, calibration factors, and calibration processes (including algorithms) used for calibrating Hanford personnel dosimeters; system operating parameters required for assurance of dosimeter processing quality control; special dose evaluation methods applied for individuals under abnormal circumstances (i.e., lost results, etc.); and methods for evaluating personnel doses from nuclear accidents. 1 ref., 14 figs., 5 tabs

Fluor Daniel Hanford implementation plan for DOE Order 5480.28. Natural phenomena hazards mitigation

International Nuclear Information System (INIS)

Conrads, T.J.

1997-01-01

Natural phenomena hazards (NPH) are unexpected acts of nature that pose a threat or danger to workers, the public, or the environment. Earthquakes, extreme winds (hurricane and tornado), snow, flooding, volcanic ashfall, and lightning strikes are examples of NPH that could occur at the Hanford Site. U.S. Department of Energy (DOE) policy requires facilities to be designed, constructed, and operated in a manner that protects workers, the public, and the environment from hazards caused by natural phenomena. DOE Order 5480.28, Natural Phenomena Hazards Mitigation, includes rigorous new natural phenomena criteria for the design of new DOE facilities, as well as for the evaluation and, if necessary, upgrade of existing DOE facilities. The Order was transmitted to Westinghouse Hanford Company in 1993 for compliance and is also identified in the Project Hanford Management Contract, Section J, Appendix C. Criteria and requirements of DOE Order 5480.28 are included in five standards, the last of which, DOE-STD-1023, was released in fiscal year 1996. Because the Order was released before all of its required standards were released, enforcement of the Order was waived pending release of the last standard and determination of an in-force date by DOE Richland Operations Office (DOE-RL). Agreement also was reached between the Management and Operations Contractor and DOE-RL that the Order would become enforceable for new structures, systems, and components (SSCS) 60 days following issue of a new order-based design criteria in HNF-PRO-97, Engineering Design and Evaluation. The order also requires that commitments addressing existing SSCs be included in an implementation plan that is to be issued 1 year following the release of the last standard. Subsequently, WHC-SP-1175, Westinghouse Hanford Company Implementation Plan for DOE Order 5480.28, Natural Phenomena Hazards Mitigation, Rev. 0, was issued in November 1996, and this document, HNF-SP-1175, Fluor Daniel Hanford

Demonstrating Reliable High Level Waste Slurry Sampling Techniques to Support Hanford Waste Processing

Energy Technology Data Exchange (ETDEWEB)

Kelly, Steven E.

2013-11-11

The Hanford Tank Operations Contractor (TOC) and the Hanford Waste Treatment and Immobilization Plant (WTP) contractor are both engaged in demonstrating mixing, sampling, and transfer system capability using simulated Hanford High-Level Waste (HL W) formulations. This work represents one of the remaining technical issues with the high-level waste treatment mission at Hanford. The TOC must demonstrate the ability to adequately mix and sample high-level waste feed to meet the WTP Waste Acceptance Criteria and Data Quality Objectives. The sampling method employed must support both TOC and WTP requirements. To facilitate information transfer between the two facilities the mixing and sampling demonstrations are led by the One System Integrated Project Team. The One System team, Waste Feed Delivery Mixing and Sampling Program, has developed a full scale sampling loop to demonstrate sampler capability. This paper discusses the full scale sampling loops ability to meet precision and accuracy requirements, including lessons learned during testing. Results of the testing showed that the Isolok(R) sampler chosen for implementation provides precise, repeatable results. The Isolok(R) sampler accuracy as tested did not meet test success criteria. Review of test data and the test platform following testing by a sampling expert identified several issues regarding the sampler used to provide reference material used to judge the Isolok's accuracy. Recommendations were made to obtain new data to evaluate the sampler's accuracy utilizing a reference sampler that follows good sampling protocol.

Demonstrating Reliable High Level Waste Slurry Sampling Techniques to Support Hanford Waste Processing

International Nuclear Information System (INIS)

Kelly, Steven E.

2013-01-01

The Hanford Tank Operations Contractor (TOC) and the Hanford Waste Treatment and Immobilization Plant (WTP) contractor are both engaged in demonstrating mixing, sampling, and transfer system capability using simulated Hanford High-Level Waste (HL W) formulations. This work represents one of the remaining technical issues with the high-level waste treatment mission at Hanford. The TOC must demonstrate the ability to adequately mix and sample high-level waste feed to meet the WTP Waste Acceptance Criteria and Data Quality Objectives. The sampling method employed must support both TOC and WTP requirements. To facilitate information transfer between the two facilities the mixing and sampling demonstrations are led by the One System Integrated Project Team. The One System team, Waste Feed Delivery Mixing and Sampling Program, has developed a full scale sampling loop to demonstrate sampler capability. This paper discusses the full scale sampling loops ability to meet precision and accuracy requirements, including lessons learned during testing. Results of the testing showed that the Isolok(R) sampler chosen for implementation provides precise, repeatable results. The Isolok(R) sampler accuracy as tested did not meet test success criteria. Review of test data and the test platform following testing by a sampling expert identified several issues regarding the sampler used to provide reference material used to judge the Isolok's accuracy. Recommendations were made to obtain new data to evaluate the sampler's accuracy utilizing a reference sampler that follows good sampling protocol

VT NAD83 USGS Quadrangle Boundaries - polygons

Data.gov (United States)

Vermont Center for Geographic Information — (Link to Metadata) Generated from exact latitude-longitude coordinates and projected from Geographic coordinates (Lat/Long) NAD83 into State Plane Meters NAD83. The...

Assimilation of NAD(+) precursors in Candida glabrata.

Science.gov (United States)

Ma, Biao; Pan, Shih-Jung; Zupancic, Margaret L; Cormack, Brendan P

2007-10-01

The yeast pathogen Candida glabrata is a nicotinamide adenine dinucleotide (NAD(+)) auxotroph and its growth depends on the environmental supply of vitamin precursors of NAD(+). C. glabrata salvage pathways defined in this article allow NAD(+) to be synthesized from three compounds - nicotinic acid (NA), nicotinamide (NAM) and nicotinamide riboside (NR). NA is salvaged through a functional Preiss-Handler pathway. NAM is first converted to NA by nicotinamidase and then salvaged by the Preiss-Handler pathway. Salvage of NR in C. glabrata occurs via two routes. The first, in which NR is phosphorylated by the NR kinase Nrk1, is independent of the Preiss-Handler pathway. The second is a novel pathway in which NR is degraded by the nucleosidases Pnp1 and Urh1, with a minor role for Meu1, and ultimately converted to NAD(+) via the nicotinamidase Pnc1 and the Preiss-Handler pathway. Using C. glabrata mutants whose growth depends exclusively on the external NA or NR supply, we also show that C. glabrata utilizes NR and to a lesser extent NA as NAD(+) sources during disseminated infection.

Preliminary assessment of blending Hanford tank wastes

International Nuclear Information System (INIS)

Geeting, J.G.H.; Kurath, D.E.

1993-03-01

A parametric study of blending Hanford tank wastes identified possible benefits from blending wastes prior to immobilization as a high level or low level waste form. Track Radioactive Components data were used as the basis for the single-shell tank (SST) waste composition, while analytical data were used for the double-shell tank (DST) composition. Limiting components were determined using the existing feed criteria for the Hanford Waste Vitrification Plant (HWVP) and the Grout Treatment Facility (GTF). Results have shown that blending can significantly increase waste loading and that the baseline quantities of immobilized waste projected for the sludge-wash pretreatment case may have been drastically underestimated, because critical components were not considered. Alternatively, the results suggest further review of the grout feed specifications and the solubility of minor components in HWVP borosilicate glass. Future immobilized waste estimates might be decreased substantially upon a thorough review of the appropriate feed specifications

Preliminary assessment of blending Hanford tank wastes

Energy Technology Data Exchange (ETDEWEB)

Geeting, J.G.H.; Kurath, D.E.

1993-03-01

A parametric study of blending Hanford tank wastes identified possible benefits from blending wastes prior to immobilization as a high level or low level waste form. Track Radioactive Components data were used as the basis for the single-shell tank (SST) waste composition, while analytical data were used for the double-shell tank (DST) composition. Limiting components were determined using the existing feed criteria for the Hanford Waste Vitrification Plant (HWVP) and the Grout Treatment Facility (GTF). Results have shown that blending can significantly increase waste loading and that the baseline quantities of immobilized waste projected for the sludge-wash pretreatment case may have been drastically underestimated, because critical components were not considered. Alternatively, the results suggest further review of the grout feed specifications and the solubility of minor components in HWVP borosilicate glass. Future immobilized waste estimates might be decreased substantially upon a thorough review of the appropriate feed specifications.

Hanford wells

International Nuclear Information System (INIS)

Chamness, M.A.; Merz, J.K.

1993-08-01

Records describing wells located on or near the Hanford Site have been maintained by Pacific Northwest Laboratory and the operating contractor, Westinghouse Hanford Company. In support of the Ground-Water Surveillance Project, portions of the data contained in these records have been compiled into the following report, which is intended to be used by those needing a condensed, tabular summary of well location and basic construction information. The wells listed in this report were constructed over a period of time spanning almost 70 years. Data included in this report were retrieved from the Hanford Envirorunental Information System (HEIS) database and supplemented with information not yet entered into HEIS. While considerable effort has been made to obtain the most accurate and complete tabulations possible of the Hanford Site wells, omissions and errors may exist. This document does not include data on lithologic logs, ground-water analyses, or specific well completion details

Hanford Site's Integrated Risk Assessment Program: No-intervention risk assessment

International Nuclear Information System (INIS)

Mahaffey, J.A.; Dukelow, J.S. Jr.; Stenner, R.D.

1994-08-01

The long-term goal of the Integrated Risk Assessment program (IRAP) is to estimate risks to workers, the public, organizations, and groups with reserved rights to Site access, the ecosystem, and natural resources to aid in managing environmental restoration and waste management at the Hanford Site. For each of these, information is needed about current risks, risks during cleanup, and endstate risks. The objective is three-fold: to determine if and when to remediate, and to what extent; to identify information unavailable but needed to make better cleanup decisions; to establish technology performance criteria for achieving desired cleanup levels; to understand costs and benefits of activities from a Site-wide perspective. The no-intervention risk, assessment is the initial evaluation of public health risks conducted under IRAP. The objective is to identify types of activities that the US Department of Energy (DOE) must accomplish for closure of the Hanford Site, defined as no further DOE intervention. There are two primary conclusions from the no-intervention risk assessment. First, some maintenance and operations activities at Hanford must be continued to protect the public from grave risks. However, when large Hanford expenditures are compared to cleanup progress, funds expended for maintenance and operations must be put in proper perspective. Second, stakeholder's emphasis on public risks at Hanford, as indicated by remediation priorities, are not in line with those estimated. The focus currently is on compliance with regulations, and on dealing with issues which are visible to stakeholders

Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases.

Science.gov (United States)

Hershberger, Kathleen A; Martin, Angelical S; Hirschey, Matthew D

2017-04-01

The coenzyme nicotinamide adenine dinucleotide (NAD + ) has key roles in the regulation of redox status and energy metabolism. NAD + depletion is emerging as a major contributor to the pathogenesis of cardiac and renal diseases and NAD + repletion strategies have shown therapeutic potential as a means to restore healthy metabolism and physiological function. The pleotropic roles of NAD + enable several possible avenues by which repletion of this coenzyme could have therapeutic efficacy. In particular, NAD + functions as a co-substrate in deacylation reactions carried out by the sirtuin family of enzymes. These NAD + -dependent deacylases control several aspects of metabolism and a wealth of data suggests that boosting sirtuin activity via NAD + supplementation might be a promising therapy for cardiac and renal pathologies. This Review summarizes the role of NAD + metabolism in the heart and kidney, and highlights the mitochondrial sirtuins as mediators of some of the beneficial effects of NAD + -boosting therapies in preclinical animal models. We surmise that modulating the NAD + -sirtuin axis is a clinically relevant approach to develop new therapies for cardiac and renal diseases.

Hanford Site Development Plan

International Nuclear Information System (INIS)

Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

1993-05-01

The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP's primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides an existing and future land use plan for the Hanford Site. The HSDP is updated annually in accordance with DOE Order 4320.1B, Site Development Planning, to reflect the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans

Comparison of Waste Feed Delivery Small Scale Mixing Demonstration Simulant to Hanford Waste

Energy Technology Data Exchange (ETDEWEB)

Wells, Beric E.; Gauglitz, Phillip A.; Rector, David R.

2012-07-10

The Hanford double-shell tank (DST) system provides the staging location for waste that will be transferred to the Hanford Tank Waste Treatment and Immobilization Plant (WTP). Specific WTP acceptance criteria for waste feed delivery describe the physical and chemical characteristics of the waste that must be met before the waste is transferred from the DSTs to the WTP. One of the more challenging requirements relates to the sampling and characterization of the undissolved solids (UDS) in a waste feed DST because the waste contains solid particles that settle and their concentration and relative proportion can change during the transfer of the waste in individual batches. A key uncertainty in the waste feed delivery system is the potential variation in UDS transferred in individual batches in comparison to an initial sample used for evaluating the acceptance criteria. To address this uncertainty, a number of small-scale mixing tests have been conducted as part of Washington River Protection Solutions' Small Scale Mixing Demonstration (SSMD) project to determine the performance of the DST mixing and sampling systems. A series of these tests have used a five-part simulant composed of particles of different size and density and designed to be equal or more challenging than AY-102 waste. This five-part simulant, however, has not been compared with the broad range of Hanford waste, and thus there is an additional uncertainty that this simulant may not be as challenging as the most difficult Hanford waste. The purpose of this study is to quantify how the current five-part simulant compares to all of the Hanford sludge waste, and to suggest alternate simulants that could be tested to reduce the uncertainty in applying the current testing results to potentially more challenging wastes.

Configuration management program plan for Hanford site systems engineering

International Nuclear Information System (INIS)

Hoffman, A.G.

1994-01-01

This plan establishes the integrated configuration management program for the evolving technical baseline developed through the systems engineering process. This configuration management program aligns with the criteria identified in the DOE Standard, DOE-STD-1073-93. Included are specific requirements for control of the systems engineering RDD-100 database, and electronic data incorporated in the database that establishes the Hanford site technical baseline

Detection of cerebral NAD+ in humans at 7T.

Science.gov (United States)

de Graaf, Robin A; De Feyter, Henk M; Brown, Peter B; Nixon, Terence W; Rothman, Douglas L; Behar, Kevin L

2017-09-01

To develop 1 H-based MR detection of nicotinamide adenine dinucleotide (NAD + ) in the human brain at 7T and validate the 1 H results with NAD + detection based on 31 P-MRS. 1 H-MR detection of NAD + was achieved with a one-dimensional double-spin-echo method on a slice parallel to the surface coil transceiver. Perturbation of the water resonance was avoided through the use of frequency-selective excitation. 31 P-MR detection of NAD + was performed with an unlocalized pulse-acquire sequence. Both 1 H- and 31 P-MRS allowed the detection of NAD + signals on every subject in 16 min. Spectral fitting provided an NAD + concentration of 107 ± 28 μM for 1 H-MRS and 367 ± 78 μM and 312 ± 65 μM for 31 P-MRS when uridine diphosphate glucose (UDPG) was excluded and included, respectively, as an overlapping signal. NAD + detection by 1 H-MRS is a simple method that comes at the price of reduced NMR visibility. NAD + detection by 31 P-MRS has near-complete NMR visibility, but it is complicated by spectral overlap with NADH and UDPG. Overall, the 1 H- and 31 P-MR methods both provide exciting opportunities to study NAD + metabolism on human brain in vivo. © 2016 International Society for Magnetic Resonance in Medicine. Magn Reson Med 78:828-835, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Resolving the Ferrocyanide Safety Issue at the Hanford Site

International Nuclear Information System (INIS)

Meacham, J.E.; Cash, R.J.; Babad, H.

1994-02-01

Considerable data have been obtained on the chemical and physical properties of ferrocyanide waste stored in Hanford Site single-shell tanks (SSTs). Theoretical analyses and ferrocyanide waste simulant studies have led to the development of fuel, moisture, and temperature criteria that define continued safe storage. Developing the criteria provides the technical basis for closing the Ferrocyanide Unreviewed Safety Question (USQ). Using the safety criteria, the ferrocyanide tanks have been ranked into one of three safety categories: Safe, Conditionally Safe, and Unsafe. All the ferrocyanide tanks are currently ranked in either the Safe or Conditionally Safe categories. Analyses of core samples taken from three ferrocyanide tanks have shown cyanide concentrations about a factor of ten lower than predicted by the original flowsheets. Hydrolytic and radiolytic destruction (aging) of the ferrocyanide matrix has occurred during the 35 plus years the waste has been stored at the Hanford Site. Because of waste aging, it is possible that all of the ferrocyanide tanks may now contain less than the 8 wt % sodium nickel ferrocyanide specified in the fuel criterion for the Safe category. Ferrocyanide tanks that remain in the Conditionally Safe category may require monitoring and surveillance to verify that the waste remains in an unreactive state. Further characterization of the tanks by core sampling and analyses should lead to resolution of the Ferrocyanide Safety Issue by September 1997

Interim Hanford Waste Management Technology Plan

International Nuclear Information System (INIS)

1985-09-01

The Interim Hanford Waste Management Technology Plan (HWMTP) is a companion document to the Interim Hanford Waste Management Plan (HWMP). A reference plan for management and disposal of all existing and certain projected future radioactive Hanford Site Defense Wastes (HSDW) is described and discussed in the HWMP. Implementation of the reference plan requires that various open technical issues be satisfactorily resolved. The principal purpose of the HWMTP is to present detailed descriptions of the technology which must be developed to close each of the technical issues associated with the reference plan identified in the HWMP. If alternative plans are followed, however, technology development efforts including costs and schedules must be changed accordingly. Technical issues addressed in the HWMTP and HWMP are those which relate to disposal of single-shell tank wastes, contaminated soil sites, solid waste burial sites, double-shell tank wastes, encapsulated 137 CsCl and 90 SrF 2 , stored and new solid transuranic (TRU) wastes, and miscellaneous wastes such as contaminated sodium metal. Among the high priority issues to be resolved are characterization of various wastes including early determination of the TRU content of future cladding removal wastes; completion of development of vitrification (Hanford Waste Vitrification Plant) and grout technology; control of subsidence in buried waste sites; and development of criteria and standards including performance assessments of systems proposed for disposal of HSDW. Estimates of the technology costs shown in this report are made on the basis that all identified tasks for all issues associated with the reference disposal plan must be performed. Elimination of, consolidation of, or reduction in the scope of individual tasks will, of course, be reflected in corresponding reduction of overall technology costs

Organic carbon in Hanford single-shell tank waste

International Nuclear Information System (INIS)

Toth, J.J.; Willingham, C.E.; Heasler, P.G.; Whitney, P.D.

1994-07-01

This report documents an analysis performed by Pacific Northwest Laboratory (PNL) involving the organic carbon laboratory measurement data for Hanford single-shell tanks (SSTS) obtained from a review of the laboratory analytical data. This activity was undertaken at the request of Westinghouse Hanford Company (WHC). The objective of this study is to provide a best estimate, including confidence levels, of total organic carbon (TOC) in each of the 149 SSTs at Hanford. The TOC analyte information presented in this report is useful as part of the criteria to identify SSTs for additional measurements or monitoring for the organic safety program. This report is a precursor to an investigation of TOC and moisture in Hanford SSTS, in order to provide best estimates for each together in one report. Measured laboratory data were obtained for 75 of the 149 SSTS. The data represent a thorough investigation of data from 224 tank characterization datasets, including core-sampling and process laboratory data. Liquid and solid phase TOC values were investigated by examining selected tanks with both reported TOC values in solid and liquid phases. Some relationships were noted, but there was no clustering of data or significance between the solid and liquid phases. A methodology was developed for estimating the distribution and levels of TOC in SSTs using a logarithmic scale and an analysis of variance (ANOVA) technique. The methodology grouped tanks according to waste type using the Sort On Radioactive Waste Type (SORWT) grouping method. The SORWT model categorizes Hanford SSTs into groups of tanks expected to exhibit similar characteristics based on major waste types and processing histories. The methodology makes use of laboratory data for the particular tank and information about the SORWT group of which the tank is a member. Recommendations for a simpler tank grouping strategy based on organic transfer records were made

Roles of Nicotinamide Adenine Dinucleotide (NAD+ in Biological Systems

Directory of Open Access Journals (Sweden)

Palmiro Poltronieri

2018-01-01

Full Text Available NAD+ has emerged as a crucial element in both bioenergetic and signaling pathways since it acts as a key regulator of cellular and organism homeostasis. NAD+ is a coenzyme in redox reactions, a donor of adenosine diphosphate-ribose (ADPr moieties in ADP-ribosylation reactions, a substrate for sirtuins, a group of histone deacetylase enzymes that use NAD+ to remove acetyl groups from proteins; NAD+ is also a precursor of cyclic ADP-ribose, a second messenger in Ca++ release and signaling, and of diadenosine tetraphosphate (Ap4A and oligoadenylates (oligo2′-5′A, two immune response activating compounds. In the biological systems considered in this review, NAD+ is mostly consumed in ADP-ribose (ADPr transfer reactions. In this review the roles of these chemical products are discussed in biological systems, such as in animals, plants, fungi and bacteria. In the review, two types of ADP-ribosylating enzymes are introduced as well as the pathways to restore the NAD+ pools in these systems.

The Leishmania nicotinamidase is essential for NAD(+) production and parasite proliferation

OpenAIRE

Gazanion, Elodie; Garcia, Deborah; Silvestre, R.; Gérard, C.; Guichou, J. F.; Labesse, G.; Seveno, Martial; Cordeiro-Da-Silva, A.; Ouaissi, A.; Sereno, Denis; Vergnes, Baptiste

2011-01-01

NAD(+) is a central cofactor that plays important roles in cellular metabolism and energy production in all living cells. Genomics-based reconstruction of NAD(+) metabolism revealed that Leishmania protozoan parasites are NAD(+) auxotrophs. Consequently, these parasites require assimilating NAD(+) precursors (nicotinamide, nicotinic acid, nicotinamide riboside) from their host environment to synthesize NAD(+) by a salvage pathway. Nicotinamidase is a key enzyme of this salvage pathway that ca...

HANFORD GROUNDWATER REMEDIATION

Energy Technology Data Exchange (ETDEWEB)

CHARBONEAU, B; THOMPSON, M; WILDE, R.; FORD, B.; GERBER, M.S.

2006-02-01

By 1990 nearly 50 years of producing plutonium put approximately 1.70E + 12 liters (450 billion gallons) of liquid wastes into the soil of the 1,518-square kilometer (586-square mile) Hanford Site in southeast Washington State. The liquid releases consisted of chemicals used in laboratory experiments, manufacturing and rinsing uranium fuel, dissolving that fuel after irradiation in Hanford's nuclear reactors, and in liquefying plutonium scraps needed to feed other plutonium-processing operations. Chemicals were also added to the water used to cool Hanford's reactors to prevent corrosion in the reactor tubes. In addition, water and acid rinses were used to clean plutonium deposits from piping in Hanford's large radiochemical facilities. All of these chemicals became contaminated with radionuclides. As Hanford raced to help win World War II, and then raced to produce materials for the Cold War, these radioactive liquid wastes were released to the Site's sandy soils. Early scientific experiments seemed to show that the most highly radioactive components of these liquids would bind to the soil just below the surface of the land, thus posing no threat to groundwater. Other experiments predicted that the water containing most radionuclides would take hundreds of years to seep into groundwater, decaying (or losing) most of its radioactivity before reaching the groundwater or subsequently flowing into the Columbia River, although it was known that some contaminants like tritium would move quickly. Evidence today, however, shows that many contaminants have reached the Site's groundwater and the Columbia River, with more on its way. Over 259 square kilometers (100 square miles) of groundwater at Hanford have contaminant levels above drinking-water standards. Also key to successfully cleaning up the Site is providing information resources and public-involvement opportunities to Hanford's stakeholders. This large, passionate, diverse, and

NAD+ biosynthesis, aging, and disease [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Sean Johnson

2018-02-01

Full Text Available Nicotinamide adenine dinucleotide (NAD+ biosynthesis and its regulation have recently been attracting markedly increasing interest. Aging is marked by a systemic decrease in NAD+ across multiple tissues. The dysfunction of NAD+ biosynthesis plays a critical role in the pathophysiologies of multiple diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders. As downstream effectors, NAD+-dependent enzymes, such as sirtuins, are involved in the progression of such disorders. These recent studies implicate NAD+ biosynthesis as a potential target for preventing and treating age-associated diseases. Indeed, new studies have demonstrated the therapeutic potential of supplementing NAD+ intermediates, such as nicotinamide mononucleotide and nicotinamide riboside, providing a proof of concept for the development of an effective anti-aging intervention.

Phenotypic and genetic characterization of NAD-dependent Pasteurellaceae from the respiratory tract of pigs and their possible pathogenetic importance

DEFF Research Database (Denmark)

Kielstein, P.; Wuthe, H.H.; Angen, Øystein

2001-01-01

. In the present study, 107 of these NAD-dependent isolates from the porcine respiratory tract, primarily from lungs with pathological changes, were investigated. On the basis of phenotypic criteria, such as haemolysis, urease, catalase, and indole formation as well as other fermentative activities, 50...

Reengineering Hanford

International Nuclear Information System (INIS)

Badalamente, R.V.; Carson, M.L.; Rhoads, R.E.

1995-03-01

The Department of Energy Richland Operations Office is in the process of reengineering its Hanford Site operations. There is a need to fundamentally rethink and redesign environmental restoration and waste management processes to achieve dramatic improvements in the quality, cost-effectiveness, and timeliness of the environmental services and products that make cleanup possible. Hanford is facing the challenge of reengineering in a complex environment in which major processes cuts across multiple government and contractor organizations and a variety of stakeholders and regulators have a great influence on cleanup activities. By doing the upfront work necessary to allow effective reengineering, Hanford is increasing the probability of its success

Reengineering Hanford

Energy Technology Data Exchange (ETDEWEB)

Badalamente, R.V.; Carson, M.L.; Rhoads, R.E.

1995-03-01

The Department of Energy Richland Operations Office is in the process of reengineering its Hanford Site operations. There is a need to fundamentally rethink and redesign environmental restoration and waste management processes to achieve dramatic improvements in the quality, cost-effectiveness, and timeliness of the environmental services and products that make cleanup possible. Hanford is facing the challenge of reengineering in a complex environment in which major processes cuts across multiple government and contractor organizations and a variety of stakeholders and regulators have a great influence on cleanup activities. By doing the upfront work necessary to allow effective reengineering, Hanford is increasing the probability of its success.

NAD Acts as an Integral Regulator of Multiple Defense Layers1[OPEN

Science.gov (United States)

Patrit, Oriane; Tcherkez, Guillaume; Gakière, Bertrand

2016-01-01

Pyridine nucleotides, such as NAD, are crucial redox carriers and have emerged as important signaling molecules in stress responses. Previously, we have demonstrated in Arabidopsis (Arabidopsis thaliana) that the inducible NAD-overproducing nadC lines are more resistant to an avirulent strain of Pseudomonas syringae pv tomato (Pst-AvrRpm1), which was associated with salicylic acid-dependent defense. Here, we have further characterized the NAD-dependent immune response in Arabidopsis. Quinolinate-induced stimulation of intracellular NAD in transgenic nadC plants enhanced resistance against a diverse range of (a)virulent pathogens, including Pst-AvrRpt2, Dickeya dadantii, and Botrytis cinerea. Characterization of the redox status demonstrated that elevated NAD levels induce reactive oxygen species (ROS) production and the expression of redox marker genes of the cytosol and mitochondrion. Using pharmacological and reverse genetics approaches, we show that NAD-induced ROS production functions independently of NADPH oxidase activity and light metabolism but depends on mitochondrial respiration, which was increased at higher NAD. We further demonstrate that NAD primes pathogen-induced callose deposition and cell death. Mass spectrometry analysis reveals that NAD simultaneously induces different defense hormones and that the NAD-induced metabolic profiles are similar to those of defense-expressing plants after treatment with pathogen-associated molecular patterns. We thus conclude that NAD triggers metabolic profiles rather similar to that of pathogen-associated molecular patterns and discuss how signaling cross talk between defense hormones, ROS, and NAD explains the observed resistance to pathogens. PMID:27621425

Hanford Site Development Plan

International Nuclear Information System (INIS)

Hathaway, H.B.; Daly, K.S.; Rinne, C.A.; Seiler, S.W.

1992-05-01

The Hanford Site Development Plan (HSDP) provides an overview of land use, infrastructure, and facility requirements to support US Department of Energy (DOE) programs at the Hanford Site. The HSDP's primary purpose is to inform senior managers and interested parties of development activities and issues that require a commitment of resources to support the Hanford Site. The HSDP provides a land use plan for the Hanford Site and presents a picture of what is currently known and anticipated in accordance with DOE Order 4320.1B. Site Development Planning. The HSDP wig be updated annually as future decisions further shape the mission and overall site development process. Further details about Hanford Site development are defined in individual area development plans

The potential regulatory roles of NAD(+) and its metabolism in autophagy.

Science.gov (United States)

Zhang, Dong-Xia; Zhang, Jia-Ping; Hu, Jiong-Yu; Huang, Yue-Sheng

2016-04-01

(Macro)autophagy mediates the bulk degradation of defective organelles, long-lived proteins and protein aggregates in lysosomes and plays a critical role in cellular and tissue homeostasis. Defective autophagy processes have been found to contribute to a variety of metabolic diseases. However, the regulatory mechanisms of autophagy are not fully understood. Increasing data indicate that nicotinamide adenine nucleotide (NAD(+)) homeostasis correlates intimately with autophagy. NAD(+) is a ubiquitous coenzyme that functions primarily as an electron carrier of oxidoreductase in multiple redox reactions. Both NAD(+) homeostasis and its metabolism are thought to play critical roles in regulating autophagy. In this review, we discuss how the regulation of NAD(+) and its metabolism can influence autophagy. We focus on the regulation of NAD(+)/NADH homeostasis and the effects of NAD(+) consumption by poly(ADP-ribose) (PAR) polymerase-1 (PARP-1), NAD(+)-dependent deacetylation by sirtuins and NAD(+) metabolites on autophagy processes and the underlying mechanisms. Future studies should provide more direct evidence for the regulation of autophagy processes by NAD(+). A better understanding of the critical roles of NAD(+) and its metabolites on autophagy will shed light on the complexity of autophagy regulation, which is essential for the discovery of new therapeutic tools for autophagy-related diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

NAD-content and metabolism in the mouse embryo and developing brain

International Nuclear Information System (INIS)

Beuningen, M. van; Streffer, C.; Beuningen, D. van

1986-01-01

Biochemical studies have shown that NAD is not only the coenzyme of dehydrogenase but also the substrate of poly-(ADPR)-synthetase which is involved in processes of cell proliferation and differentiation. The NAD and protein content was determined in the total embryo and in the CNS 9 to 13 days p.c. The embryos were X-irradiated 9 days p.c. The NAD content increased in the total mouse embryo during the early organogenesis. At the later period a decrease of the NAD content per mg protein was observed. This latter effect was apparently due to an increase of the NAD glycohydrolase activity. This enzyme degrades NAD. A similar development was observed in the developing mouse brain. However, the maximal NAD content per mg protein occurred on day 10 p.c. One of the enzyme activities, which are responsible for NAD synthesis, NMN-pyrophosphorylase, also increased in the brain at the same time. After the injection of C 14-nicotinamide, a precursor of NAD, it was observed that the radioactivity mainly appeared in nicotinamide and NAD. With progressing embryological development less nicotinamide was taken up by the embryonic tissue. When the embryos were X-irradiated on day 9 p.c. with 1.8 Gy the increase of NAD was considerably reduced during the next days, so that also the NAD level per mg protein was reduced. Also the NAD biosynthesis apparently decreased. This was shown again by the reduced NMN-pyrophosphorylase activity. The dose dependance of these effects was studied in the dose range 0.48-1.8 Gy. Two days p.r. most of the radiation effects were normalized again and at later periods even an overshoot of the enzyme activity was observed. The possible relevance of these effects for cell proliferation will be discussed. (orig.)

NAMPT-mediated salvage synthesis of NAD+ controls morphofunctional changes of macrophages.

Directory of Open Access Journals (Sweden)

Gerda Venter

Full Text Available Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H (i.e. NAD+ and NADH and NADP(H (i.e. NADP+ and NADPH play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT, found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+'s cytosolic role in the regulation of morphofunctional characteristics of macrophages.

Hanford wells

International Nuclear Information System (INIS)

McGhan, V.L.; Myers, D.A.; Damschen, D.W.

1976-03-01

The Hanford Reservation contains about 2100 wells constructed from pre-Hanford Works to the present. As of Jan. 1976, about 1800 wells still exist, 850 of which were drilled to the groundwater table; 700 still contain water. This report provides the most complete documentation of these wells and supersedes all previous compilations, including BNWL-1739

The NAD/NARB System: Advertising Self-Regulation at Work.

Science.gov (United States)

Hays, Robert

Self-regulation, as defined by the National Advertising Division/National Advertising Review Board (NAD/NARB), is a process whereby the advertising industry regulates itself and turns to the federal government only if the system fails. The NAD/NARB system involves a two-step process: complaints are initially handled by the NAD and then are either…

Implementation guide for Hanford Analytical Services Quality Assurance Plan

International Nuclear Information System (INIS)

1994-09-01

This implementation guide for the Hanford Analytical Services Quality Assurance Plan (HASQAP) was developed by the US Department of Energy, Richland Operations Office (RL) Waste Management Division, Analytical Services Branch. This plan formally presents RL's direction for Hanford Sitewide implementation of the HASQAP. The HASQAP establishes a uniform standard for quality requirements to meet US Department of Energy Order 5700.6C, Quality Assurance (10 CFR 830.120, ''Quality Assurance Requirements''), and is intended to satisfy the Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement) requirements for ''Guidance on Preparation of Laboratory Quality Assurance Plans''. The quality assurance criteria specified in the HASQAP shall serve as a baseline for implementing quality management systems for the laboratories that provide analytical services, for data requesters and users, and for oversight organizations that monitor the data-generation process. Affected organizations shall implement the HASQAP requirements that are applicable to their work scope. Full implementation of the HASQAP is scheduled to occur by August 1995. RL will work with the US Environmental Protection Agency (EPA) and Washington State Department of Ecology (Ecology) to have the HASQAP document incorporated into Appendix F of the Tri-Party Agreement by early Fiscal Year 1996

Hanford beta-gamma personnel dosimeter prototypes and evaluation

International Nuclear Information System (INIS)

Fix, J.J.; Holbrook, K.L.; Soldat, K.L.

1983-04-01

Upgraded and modified Hanford dosimeter prototypes were evaluated for possible use at Hanford as a primary beta-gamma dosimeter. All prototypes were compatible with the current dosimeter card and holder design, as well as processing with the automated Hanford readers. Shallow- and deep-dose response was determined for selected prototypes using several beta sources, K-fluorescent x rays and filtered x-ray techniques. All prototypes included a neutron sensitive chip. A progressive evaluation of the performance of each of the upgrades to the current dosimeter is described. In general, the performance of the current dosimeter can be upgraded using individual chip sensitivity factors to improve precision and an improved algorithm to minimize bias. The performance of this dosimeter would be adequate to pass all categories of the ANSI N13.11 performance criteria for dosimeter procesors, provided calibration techniques compatible with irradiations adopted in the standard were conducted. The existing neutron capability of the dosimeter could be retained. Better dosimeter performance to beta-gamma radiation can be achieved by modifying the Hanford dosimeter so that four of the five chip positions are devoted to calculating these doses instead of the currently used two chip positions. A neutron sensitive chip was used in the 5th chip position, but all modified dosimeter prototypes would be incapable of discriminating between thermal and epithermal neutrons. An improved low energy beta response can be achieved for the current dosimeter and all prototypes considered by eliminating the security credential. Further improvement can be obtained by incorporating the 15-mil thick TLD-700 chips

NAD+/NADH and skeletal muscle mitochondrial adaptations to exercise

Science.gov (United States)

White, Amanda T.

2012-01-01

The pyridine nucleotides, NAD+ and NADH, are coenzymes that provide oxidoreductive power for the generation of ATP by mitochondria. In skeletal muscle, exercise perturbs the levels of NAD+, NADH, and consequently, the NAD+/NADH ratio, and initial research in this area focused on the contribution of redox control to ATP production. More recently, numerous signaling pathways that are sensitive to perturbations in NAD+(H) have come to the fore, as has an appreciation for the potential importance of compartmentation of NAD+(H) metabolism and its subsequent effects on various signaling pathways. These pathways, which include the sirtuin (SIRT) proteins SIRT1 and SIRT3, the poly(ADP-ribose) polymerase (PARP) proteins PARP1 and PARP2, and COOH-terminal binding protein (CtBP), are of particular interest because they potentially link changes in cellular redox state to both immediate, metabolic-related changes and transcriptional adaptations to exercise. In this review, we discuss what is known, and not known, about the contribution of NAD+(H) metabolism and these aforementioned proteins to mitochondrial adaptations to acute and chronic endurance exercise. PMID:22436696

NAMPT and NAMPT-controlled NAD Metabolism in Vascular Repair.

Science.gov (United States)

Wang, Pei; Li, Wen-Lin; Liu, Jian-Min; Miao, Chao-Yu

2016-06-01

Vascular repair plays important roles in postischemic remodeling and rehabilitation in cardiovascular and cerebrovascular disease, such as stroke and myocardial infarction. Nicotinamide adenine dinucleotide (NAD), a well-known coenzyme involved in electron transport chain for generation of adenosine triphosphate, has emerged as an important controller regulating various biological signaling pathways. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme for NAD biosynthesis in mammals. NAMPT may also act in a nonenzymatic manner, presumably mediated by unknown receptor(s). Rapidly accumulating data in the past decade show that NAMPT and NAMPT-controlled NAD metabolism regulate fundamental biological functions in endothelial cells, vascular smooth muscle cells, and endothelial progenitor cells. The NAD-consuming proteins, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38, may contribute to the regulatory effects of NAMPT-NAD axis in these cells and vascular repair. This review discusses the current data regarding NAMPT and NAMPT-controlled NAD metabolism in vascular repair and the clinical potential translational application of NAMPT-related products in treatment of cardiovascular and cerebrovascular disease.

Novel pathway of NAD metabolism in Aspergillus niger

International Nuclear Information System (INIS)

Kuwahara, Masaaki

1977-01-01

New steps of NAD metabolism were shown in Aspergillus niger. Radioactive nicotinic acid and nicotinamide were incorporated into nicotinamide ribose diphosphate ribose (NAmRDPR), which had been isolated from the culture filtrate. The enzyme preparation of the mold degraded NAmRDPR to form nicotinamide mononucleotide and nicotinic acid under the neutral and alkaline conditions. In the acid extracts of the mycelia grown on the radioactive precursors, high level of radioactivity was detected on NAD. The experimental results showed that the Preiss-Handler pathway and the NAD cycling system function in the NAD biosynthesis in A. niger. A part of the radioactive precursors was also incorporated into nicotinic acid ribonucleoside, which was thought to be formed from nicotinic acid mononucleotide. (auth.)

Mission analysis report for the Hanford Tanks Initiative

International Nuclear Information System (INIS)

Schaus, P.S.

1997-01-01

This mission analysis report for the Hanford Tanks Initiative (HTI) supports the Hanford Site's Single-Shell Tank (SST) Waste Retrieval Program in its commitment to remove waste from the SSTs for treatment and final closure of the tanks. The results of the HTI will support the US Department of Energy's (DOE) privatization of retrieval efforts. This report addresses the HTI problem statement: Alternative technologies to past practice sluicing (PPS) have not yet been demonstrated to remove the hard heel from a sluiced tank or to remove waste from a leaking SST. Nor have performance-based criteria for cleanout and closure been demonstrated to the degree necessary to validate them as technically and economically achievable. This report also defines the mission statement and mission boundaries; the known interfaces, both programmatic and project; the mission level requirements; the test and evaluation methodology; and measures of success

Impaired NAD+ Metabolism in Neuronal Dysfunction in Critical Conditions

Directory of Open Access Journals (Sweden)

A. V Salmina

2008-01-01

Full Text Available The present views of the pathogenesis of neuronal dysfunction in critical conditions are analyzed, by taking into account of impairments of cellular NAD+ metabolism, the activity of NAD+-converting enzymes, including ADP-ribosyl cyclase/CD38, the possibilities of developing new neuroprotective strategies. Key words: neuronal dysfunction, ADP-rybosyl cyclase/CD38, NAD+, critical condition.

VT NAD83 USGS Quadrangle Boundaries - corner points

Data.gov (United States)

Vermont Center for Geographic Information — (Link to Metadata) Generated from exact latitude-longitude coordinates and projected from Geographic coordinates (Lat/Long) NAD83 into State Plane Meters NAD83. The...

The evolutionary portrait of metazoan NAD salvage.

Science.gov (United States)

Carneiro, João; Duarte-Pereira, Sara; Azevedo, Luísa; Castro, L Filipe C; Aguiar, Paulo; Moreira, Irina S; Amorim, António; Silva, Raquel M

2013-01-01

Nicotinamide Adenine Dinucleotide (NAD) levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs) and Nicotinamidases (PNCs) have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

Uridine monophosphate synthetase enables eukaryotic de novo NAD+ biosynthesis from quinolinic acid.

Science.gov (United States)

McReynolds, Melanie R; Wang, Wenqing; Holleran, Lauren M; Hanna-Rose, Wendy

2017-07-07

NAD + biosynthesis is an attractive and promising therapeutic target for influencing health span and obesity-related phenotypes as well as tumor growth. Full and effective use of this target for therapeutic benefit requires a complete understanding of NAD + biosynthetic pathways. Here, we report a previously unrecognized role for a conserved phosphoribosyltransferase in NAD + biosynthesis. Because a required quinolinic acid phosphoribosyltransferase (QPRTase) is not encoded in its genome, Caenorhabditis elegans are reported to lack a de novo NAD + biosynthetic pathway. However, all the genes of the kynurenine pathway required for quinolinic acid (QA) production from tryptophan are present. Thus, we investigated the presence of de novo NAD + biosynthesis in this organism. By combining isotope-tracing and genetic experiments, we have demonstrated the presence of an intact de novo biosynthesis pathway for NAD + from tryptophan via QA, highlighting the functional conservation of this important biosynthetic activity. Supplementation with kynurenine pathway intermediates also boosted NAD + levels and partially reversed NAD + -dependent phenotypes caused by mutation of pnc-1 , which encodes a nicotinamidase required for NAD + salvage biosynthesis, demonstrating contribution of de novo synthesis to NAD + homeostasis. By investigating candidate phosphoribosyltransferase genes in the genome, we determined that the conserved uridine monophosphate phosphoribosyltransferase (UMPS), which acts in pyrimidine biosynthesis, is required for NAD + biosynthesis in place of the missing QPRTase. We suggest that similar underground metabolic activity of UMPS may function in other organisms. This mechanism for NAD + biosynthesis creates novel possibilities for manipulating NAD + biosynthetic pathways, which is key for the future of therapeutics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Summary report on the development of a cement-based formula to immobilize Hanford facility waste

International Nuclear Information System (INIS)

Gilliam, T.M.; McDaniel, E.W.; Dole, L.R.; Friedman, H.A.; Loflin, J.A.; Mattus, A.J.; Morgan, I.L.; Tallent, O.K.; West, G.A.

1987-09-01

This report recommends a cement-based grout formula to immobilize Hanford Facility Waste in the Transportable Grout Facility (TGF). Supporting data confirming compliance with all TGF performance criteria are presented. 9 refs., 24 figs., 50 tabs

Stabilizing plutonium materials at Hanford: systems engineering for PFP transition project effort on DNFSB 94-1

Energy Technology Data Exchange (ETDEWEB)

Huber, T.E., Westinghouse Hanford

1996-07-02

This report discusses the basic objectives of the stabilization and packaging activities at the Plutonium Finishing Plant that satisfy the Defense Nuclear Facility Safety Board Recommendation 94-1 by transforming the plutonium materials at hanford into forms or conditions which are suitable for safe storage to appropriate storage criteria; or discard that meets appropriate waste acceptance criteria.

Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae

Science.gov (United States)

Kato, Michiko; Lin, Su-Ju

2014-01-01

Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD+ is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD+ homeostasis is essential for proper cellular function and aberrant NAD+ metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD+ metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD+ metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD+ metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD+ metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD+ metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD+-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD+ intermediates, and their potential roles in NAD+ homeostasis. To date, it remains unclear how NAD+ and NAD+ intermediates shuttle between different

Surrogate analyte approach for quantitation of endogenous NAD(+) in human acidified blood samples using liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Science.gov (United States)

Liu, Liling; Cui, Zhiyi; Deng, Yuzhong; Dean, Brian; Hop, Cornelis E C A; Liang, Xiaorong

2016-02-01

A high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS) assay for the quantitative determination of NAD(+) in human whole blood using a surrogate analyte approach was developed and validated. Human whole blood was acidified using 0.5N perchloric acid at a ratio of 1:3 (v:v, blood:perchloric acid) during sample collection. 25μL of acidified blood was extracted using a protein precipitation method and the resulting extracts were analyzed using reverse-phase chromatography and positive electrospray ionization mass spectrometry. (13)C5-NAD(+) was used as the surrogate analyte for authentic analyte, NAD(+). The standard curve ranging from 0.250 to 25.0μg/mL in acidified human blood for (13)C5-NAD(+) was fitted to a 1/x(2) weighted linear regression model. The LC-MS/MS response between surrogate analyte and authentic analyte at the same concentration was obtained before and after the batch run. This response factor was not applied when determining the NAD(+) concentration from the (13)C5-NAD(+) standard curve since the percent difference was less than 5%. The precision and accuracy of the LC-MS/MS assay based on the five analytical QC levels were well within the acceptance criteria from both FDA and EMA guidance for bioanalytical method validation. Average extraction recovery of (13)C5-NAD(+) was 94.6% across the curve range. Matrix factor was 0.99 for both high and low QC indicating minimal ion suppression or enhancement. The validated assay was used to measure the baseline level of NAD(+) in 29 male and 21 female human subjects. This assay was also used to study the circadian effect of endogenous level of NAD(+) in 10 human subjects. Copyright © 2015 Elsevier B.V. All rights reserved.

Metabolic profiling of alternative NAD biosynthetic routes in mouse tissues.

Directory of Open Access Journals (Sweden)

Valerio Mori

Full Text Available NAD plays essential redox and non-redox roles in cell biology. In mammals, its de novo and recycling biosynthetic pathways encompass two independent branches, the "amidated" and "deamidated" routes. Here we focused on the indispensable enzymes gating these two routes, i.e. nicotinamide mononucleotide adenylyltransferase (NMNAT, which in mammals comprises three distinct isozymes, and NAD synthetase (NADS. First, we measured the in vitro activity of the enzymes, and the levels of all their substrates and products in a number of tissues from the C57BL/6 mouse. Second, from these data, we derived in vivo estimates of enzymes'rates and quantitative contributions to NAD homeostasis. The NMNAT activity, mainly represented by nuclear NMNAT1, appears to be high and nonrate-limiting in all examined tissues, except in blood. The NADS activity, however, appears rate-limiting in lung and skeletal muscle, where its undetectable levels parallel a relative accumulation of the enzyme's substrate NaAD (nicotinic acid adenine dinucleotide. In all tissues, the amidated NAD route was predominant, displaying highest rates in liver and kidney, and lowest in blood. In contrast, the minor deamidated route showed higher relative proportions in blood and small intestine, and higher absolute values in liver and small intestine. Such results provide the first comprehensive picture of the balance of the two alternative NAD biosynthetic routes in different mammalian tissues under physiological conditions. This fills a gap in the current knowledge of NAD biosynthesis, and provides a crucial information for the study of NAD metabolism and its role in disease.

NAMPT-Mediated Salvage Synthesis of NAD+ Controls Morphofunctional Changes of Macrophages

Science.gov (United States)

Venter, Gerda; Oerlemans, Frank T. J. J.; Willemse, Marieke; Wijers, Mietske; Fransen, Jack A. M.; Wieringa, Bé

2014-01-01

Functional morphodynamic behavior of differentiated macrophages is strongly controlled by actin cytoskeleton rearrangements, a process in which also metabolic cofactors ATP and NAD(H) (i.e. NAD+ and NADH) and NADP(H) (i.e. NADP+ and NADPH) play an essential role. Whereas the link to intracellular ATP availability has been studied extensively, much less is known about the relationship between actin cytoskeleton dynamics and intracellular redox state and NAD+-supply. Here, we focus on the role of nicotinamide phosphoribosyltransferase (NAMPT), found in extracellular form as a cytokine and growth factor, and in intracellular form as one of the key enzymes for the production of NAD+ in macrophages. Inhibition of NAD+ salvage synthesis by the NAMPT-specific drug FK866 caused a decrease in cytosolic NAD+ levels in RAW 264.7 and Maf-DKO macrophages and led to significant downregulation of the glycolytic flux without directly affecting cell viability, proliferation, ATP production capacity or mitochondrial respiratory activity. Concomitant with these differential metabolic changes, the capacity for phagocytic ingestion of particles and also substrate adhesion of macrophages were altered. Depletion of cytoplasmic NAD+ induced cell-morphological changes and impaired early adhesion in phagocytosis of zymosan particles as well as spreading performance. Restoration of NAD+ levels by NAD+, NMN, or NADP+ supplementation reversed the inhibitory effects of FK866. We conclude that direct coupling to local, actin-based, cytoskeletal dynamics is an important aspect of NAD+’s cytosolic role in the regulation of morphofunctional characteristics of macrophages. PMID:24824795

Historical genesis of Hanford Site wastes

International Nuclear Information System (INIS)

Gerber, M.S.

1991-01-01

This paper acquaints the audience with historical waste practices and policies as they changed over the years at the Hanford Site, and with the generation of the major waste streams of concern in Hanford Site clean-up today. The paper also describes the founding and basic operating history of the Hanford Site, including World War 11 construction and operations, three major postwar expansions (1947-55), the peak years of production (1956-63), production phase downs (1964-the present), and some past suggestions and efforts to chemically treat, open-quotes fractionate,close quotes and/or immobilize Hanford's wastes. Recent events, including the designation of the Hanford Site as the open-quotes flagshipclose quotes of Department of Energy (DOE) waste remediation efforts and the signing of the landmark Hanford Federal Facility Agreement and Consent Order (Tri-Party Agreement), have generated new interest in Hanford's history. Clean-up milestones dictated in this agreement demand information about how, when, in what quantities and mixtures, and under what conditions, Hanford Site wastes were generated and released. This paper presents original, primary-source research into the waste history of the Hanford Site. The earliest, 1940s knowledge base, assumptions and calculations about radioactive and chemical discharges, as discussed in the memos, correspondence and reports of the original Hanford Site (then Hanford Engineer Works) builders and operators, are reviewed. The growth of knowledge, research efforts, and subsequent changes in Site waste disposal policies and practices are traced. Finally, the paper places the current Hanford Site waste remediation endeavors in the broad context of American and world history

Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity.

Science.gov (United States)

Ting, Kai Yiu; Leung, Christina F P; Graeff, Richard M; Lee, Hon Cheung; Hao, Quan; Kotaka, Masayo

2016-03-01

Cyclic ADP-ribose (cADPR) mobilizes intracellular Ca(2+) stores and activates Ca(2+) influx to regulate a wide range of physiological processes. It is one of the products produced from the catalysis of NAD(+) by the multifunctional CD38/ADP-ribosyl cyclase superfamily. After elimination of the nicotinamide ring by the enzyme, the reaction intermediate of NAD(+) can either be hydrolyzed to form linear ADPR or cyclized to form cADPR. We have previously shown that human CD38 exhibits a higher preference towards the hydrolysis of NAD(+) to form linear ADPR while Aplysia ADP-ribosyl cyclase prefers cyclizing NAD(+) to form cADPR. In this study, we characterized the enzymatic properties of porcine CD38 and revealed that it has a prominent secondary NAD(+) cyclase activity producing cADPR. We also determined the X-ray crystallographic structures of porcine CD38 and were able to observe conformational flexibility at the base of the active site of the enzyme which allow the NAD(+) reaction intermediate to adopt conformations resulting in both hydrolysis and cyclization forming linear ADPR and cADPR respectively. © 2016 The Protein Society.

Hanford site environment

International Nuclear Information System (INIS)

Isaacson, R.E.

1976-01-01

A synopsis is given of the detailed characterization of the existing environment at Hanford. The following aspects are covered: demography, land use, meteorology, geology, hydrology, and seismology. It is concluded that Hanford is one of the most extensively characterized nuclear sites

Managing risk at Hanford

International Nuclear Information System (INIS)

Hesser, W.A.; Stillwell, W.G.; Rutherford, W.A.

1994-01-01

Clearly, there is sufficient motivation from Washington for the Hanford community to pay particular attention to the risks associated with the substantial volumes of radiological, hazardous, and mixed waste at Hanford. But there is also another reason for emphasizing risk: Hanford leaders have come to realize that their decisions must consider risk and risk reduction if those decisions are to be technically sound, financially affordable, and publicly acceptable. The 560-square miles of desert land is worth only a few thousand dollars an acre (if that) -- hardly enough to justify the almost two billion dollars that will be spent at Hanford this year. The benefit of cleaning up the Hanford Site is not the land but the reduction of potential risk to the public and the environment for future generations. If risk reduction is our ultimate goal, decisions about priority of effort and resource allocation must consider those risks, now and in the future. The purpose of this paper is to describe how Hanford is addressing the issues of risk assessment, risk management, and risk-based decision making and to share some of our experiences in these areas

FLUOR HANFORD (FH) MAKES CLEANUP A REALITY IN NEARLY 11 YEARS AT HANFORD

Energy Technology Data Exchange (ETDEWEB)

GERBER, M.S.

2007-05-24

For nearly 11 years, Fluor Hanford has been busy cleaning up the legacy of nuclear weapons production at one of the Department of Energy's (DOE'S) major sites in the United States. As prime nuclear waste cleanup contractor at the vast Hanford Site in southeastern Washington state, Fluor Hanford has changed the face of cleanup. Fluor beginning on October 1, 1996, Hanford Site cleanup was primarily a ''paper exercise.'' The Tri-Party Agreement, officially called the Hanford Federal Facility Agreement and Consent Order - the edict governing cleanup among the DOE, U.S. Environmental Protection Agency (EPA) and Washington state - was just seven years old. Milestones mandated in the agreement up until then had required mainly waste characterization, reporting, and planning, with actual waste remediation activities off in the future. Real work, accessing waste ''in the field'' - or more literally in huge underground tanks, decaying spent fuel POO{approx}{approx}S, groundwater, hundreds of contaminated facilities, solid waste burial grounds, and liquid waste disposal sites -began in earnest under Fluor Hanford. The fruits of labors initiated, completed and/or underway by Fluor Hanford can today be seen across the site. Spent nuclear fuel is buttoned up in secure, dry containers stored away from regional water resources, reactive plutonium scraps are packaged in approved containers, transuranic (TRU) solid waste is being retrieved from burial trenches and shipped offsite for permanent disposal, contaminated facilities are being demolished, contaminated groundwater is being pumped out of aquifers at record rates, and many other inventive solutions are being applied to Hanford's most intransigent nuclear wastes. (TRU) waste contains more than 100 nanocuries per gram, and contains isotopes higher than uranium on the Periodic Table of the Elements. (A nanocurie is one-billionth of a curie.) At the same time, Fluor Hanford

Test plan for Fauske and Associates to perform tube propagation experiments with simulated Hanford tank wastes

International Nuclear Information System (INIS)

Carlson, C.D.; Babad, H.

1996-05-01

This test plan, prepared at Pacific Northwest National Laboratory for Westinghouse Hanford Company, provides guidance for performing tube propagation experiments on simulated Hanford tank wastes and on actual tank waste samples. Simulant compositions are defined and an experimental logic tree is provided for Fauske and Associates (FAI) to perform the experiments. From this guidance, methods and equipment for small-scale tube propagation experiments to be performed at the Hanford Site on actual tank samples will be developed. Propagation behavior of wastes will directly support the safety analysis (SARR) for the organic tanks. Tube propagation may be the definitive tool for determining the relative reactivity of the wastes contained in the Hanford tanks. FAI have performed tube propagation studies previously on simple two- and three-component surrogate mixtures. The simulant defined in this test plan more closely represents actual tank composition. Data will be used to support preparation of criteria for determining the relative safety of the organic bearing wastes

Engineering Escherichia coli Nicotinic Acid Mononucleotide Adenylyltransferase for Fully Active Amidated NAD Biosynthesis.

Science.gov (United States)

Wang, Xueying; Zhou, Yongjin J; Wang, Lei; Liu, Wujun; Liu, Yuxue; Peng, Chang; Zhao, Zongbao K

2017-07-01

NAD and its reduced form NADH function as essential redox cofactors and have major roles in determining cellular metabolic features. NAD can be synthesized through the deamidated and amidated pathways, for which the key reaction involves adenylylation of nicotinic acid mononucleotide (NaMN) and nicotinamide mononucleotide (NMN), respectively. In Escherichia coli , NAD de novo biosynthesis depends on the protein NadD-catalyzed adenylylation of NaMN to nicotinic acid adenine dinucleotide (NaAD), followed by NAD synthase-catalyzed amidation. In this study, we engineered NadD to favor NMN for improved amidated pathway activity. We designed NadD mutant libraries, screened by a malic enzyme-coupled colorimetric assay, and identified two variants, 11B4 (Y84V/Y118D) and 16D8 (A86W/Y118N), with a high preference for NMN. Whereas in the presence of NMN both variants were capable of enabling the viability of cells of E. coli BW25113-derived NAD-auxotrophic strain YJE003, for which the last step of the deamidated pathway is blocked, the 16D8 expression strain could grow without exogenous NMN and accumulated a higher cellular NAD(H) level than BW25113 in the stationary phase. These mutants established fully active amidated NAD biosynthesis and offered a new opportunity to manipulate NAD metabolism for biocatalysis and metabolic engineering. IMPORTANCE Adenylylation of nicotinic acid mononucleotide (NaMN) and adenylylation of nicotinamide mononucleotide (NMN), respectively, are the key steps in the deamidated and amidated pathways for NAD biosynthesis. In most organisms, canonical NAD biosynthesis follows the deamidated pathway. Here we engineered Escherichia coli NaMN adenylyltransferase to favor NMN and expressed the mutant enzyme in an NAD-auxotrophic E. coli strain that has the last step of the deamidated pathway blocked. The engineered strain survived in M9 medium, which indicated the implementation of a functional amidated pathway for NAD biosynthesis. These results enrich

Hanford Site Transuranic (TRU) Waste Certification Plan

International Nuclear Information System (INIS)

GREAGER, T.M.

2000-01-01

As a generator of transuranic (TRU) and TRU mixed waste destined for disposal at the Waste Isolation Pilot Plant (WIPP), the Hanford Site must ensure that its TRU waste meets the requirements of US. Department of Energy (DOE) 0 435.1, ''Radioactive Waste Management,'' and the Contact-Handled (CH) Transuranic Waste Acceptance Criteria for the Waste Isolation Pilot Plant (WIPP-WAC). WIPP-WAC requirements are derived from the WIPP Technical Safety Requirements, WIPP Safety Analysis Report, TRUPACT-II SARP, WIPP Land Withdrawal Act, WIPP Hazardous Waste Facility Permit, and Title 40 Code of Federal Regulations (CFR) 191/194 Compliance Certification Decision. The WIPP-WAC establishes the specific physical, chemical, radiological, and packaging criteria for acceptance of defense TRU waste shipments at WIPP. The WPP-WAC also requires that participating DOE TRU waste generator/treatment/storage sites produce site-specific documents, including a certification plan, that describe their program for managing TRU waste and TRU waste shipments before transferring waste to WIPP. Waste characterization activities provide much of the data upon which certification decisions are based. Waste characterization requirements for TRU waste and TRU mixed waste that contains constituents regulated under the Resource Conservation and Recovery Act (RCRA) are established in the WIPP Hazardous Waste Facility Permit Waste Analysis Plan (WAP). The Hanford Site Quality Assurance Project Plan (QAPjP) (HNF-2599) implements the applicable requirements in the WAP and includes the qualitative and quantitative criteria for making hazardous waste determinations. The Hanford Site must also ensure that its TRU waste destined for disposal at WPP meets requirements for transport in the Transuranic Package Transporter-11 (TRUPACT-11). The US. Nuclear Regulatory Commission (NRC) establishes the TRUPACT-11 requirements in the Safety Analysis Report for the TRUPACT-II Shipping Package (TRUPACT-11 SARP). In

NAD Deficiency, Congenital Malformations, and Niacin Supplementation.

Science.gov (United States)

Shi, Hongjun; Enriquez, Annabelle; Rapadas, Melissa; Martin, Ella M M A; Wang, Roni; Moreau, Julie; Lim, Chai K; Szot, Justin O; Ip, Eddie; Hughes, James N; Sugimoto, Kotaro; Humphreys, David T; McInerney-Leo, Aideen M; Leo, Paul J; Maghzal, Ghassan J; Halliday, Jake; Smith, Janine; Colley, Alison; Mark, Paul R; Collins, Felicity; Sillence, David O; Winlaw, David S; Ho, Joshua W K; Guillemin, Gilles J; Brown, Matthew A; Kikuchi, Kazu; Thomas, Paul Q; Stocker, Roland; Giannoulatou, Eleni; Chapman, Gavin; Duncan, Emma L; Sparrow, Duncan B; Dunwoodie, Sally L

2017-08-10

Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations. We tested the function of the variant by using assays of in vitro enzyme activity and by quantifying metabolites in patient plasma. We engineered mouse models with similar variants using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 system. Variants were identified in two genes that encode enzymes of the kynurenine pathway, 3-hydroxyanthranilic acid 3,4-dioxygenase (HAAO) and kynureninase (KYNU). Three patients carried homozygous variants predicting loss-of-function changes in the HAAO or KYNU proteins (HAAO p.D162*, HAAO p.W186*, or KYNU p.V57Efs*21). Another patient carried heterozygous KYNU variants (p.Y156* and p.F349Kfs*4). The mutant enzymes had greatly reduced activity in vitro. Nicotinamide adenine dinucleotide (NAD) is synthesized de novo from tryptophan through the kynurenine pathway. The patients had reduced levels of circulating NAD. Defects similar to those in the patients developed in the embryos of Haao-null or Kynu-null mice owing to NAD deficiency. In null mice, the prevention of NAD deficiency during gestation averted defects. Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice. (Funded by the National Health and Medical Research Council of Australia and others.).

Regulation of NAD+ metabolism, signaling and compartmentalization in the yeast Saccharomyces cerevisiae.

Science.gov (United States)

Kato, Michiko; Lin, Su-Ju

2014-11-01

Pyridine nucleotides are essential coenzymes in many cellular redox reactions in all living systems. In addition to functioning as a redox carrier, NAD(+) is also a required co-substrate for the conserved sirtuin deacetylases. Sirtuins regulate transcription, genome maintenance and metabolism and function as molecular links between cells and their environment. Maintaining NAD(+) homeostasis is essential for proper cellular function and aberrant NAD(+) metabolism has been implicated in a number of metabolic- and age-associated diseases. Recently, NAD(+) metabolism has been linked to the phosphate-responsive signaling pathway (PHO pathway) in the budding yeast Saccharomyces cerevisiae. Activation of the PHO pathway is associated with the production and mobilization of the NAD(+) metabolite nicotinamide riboside (NR), which is mediated in part by PHO-regulated nucleotidases. Cross-regulation between NAD(+) metabolism and the PHO pathway has also been reported; however, detailed mechanisms remain to be elucidated. The PHO pathway also appears to modulate the activities of common downstream effectors of multiple nutrient-sensing pathways (Ras-PKA, TOR, Sch9/AKT). These signaling pathways were suggested to play a role in calorie restriction-mediated beneficial effects, which have also been linked to Sir2 function and NAD(+) metabolism. Here, we discuss the interactions of these pathways and their potential roles in regulating NAD(+) metabolism. In eukaryotic cells, intracellular compartmentalization facilitates the regulation of enzymatic functions and also concentrates or sequesters specific metabolites. Various NAD(+)-mediated cellular functions such as mitochondrial oxidative phosphorylation are compartmentalized. Therefore, we also discuss several key players functioning in mitochondrial, cytosolic and vacuolar compartmentalization of NAD(+) intermediates, and their potential roles in NAD(+) homeostasis. To date, it remains unclear how NAD(+) and NAD(+) intermediates

The evolutionary portrait of metazoan NAD salvage.

Directory of Open Access Journals (Sweden)

João Carneiro

Full Text Available Nicotinamide Adenine Dinucleotide (NAD levels are essential for cellular homeostasis and survival. Main sources of intracellular NAD are the salvage pathways from nicotinamide, where Nicotinamide phosphoribosyltransferases (NAMPTs and Nicotinamidases (PNCs have a key role. NAMPTs and PNCs are important in aging, infection and disease conditions such as diabetes and cancer. These enzymes have been considered redundant since either one or the other exists in each individual genome. The co-occurrence of NAMPT and PNC was only recently detected in invertebrates though no structural or functional characterization exists for them. Here, using expression and evolutionary analysis combined with homology modeling and protein-ligand docking, we show that both genes are expressed simultaneously in key species of major invertebrate branches and emphasize sequence and structural conservation patterns in metazoan NAMPT and PNC homologues. The results anticipate that NAMPTs and PNCs are simultaneously active, raising the possibility that NAD salvage pathways are not redundant as both are maintained to fulfill the requirement for NAD production in some species.

Vibrio Phage KVP40 Encodes a Functional NAD+ Salvage Pathway.

Science.gov (United States)

Lee, Jae Yun; Li, Zhiqun; Miller, Eric S

2017-05-01

The genome of T4-type Vibrio bacteriophage KVP40 has five genes predicted to encode proteins of pyridine nucleotide metabolism, of which two, nadV and natV , would suffice for an NAD + salvage pathway. NadV is an apparent nicotinamide phosphoribosyltransferase (NAmPRTase), and NatV is an apparent bifunctional nicotinamide mononucleotide adenylyltransferase (NMNATase) and nicotinamide-adenine dinucleotide pyrophosphatase (Nudix hydrolase). Genes encoding the predicted salvage pathway were cloned and expressed in Escherichia coli , the proteins were purified, and their enzymatic properties were examined. KVP40 NadV NAmPRTase is active in vitro , and a clone complements a Salmonella mutant defective in both the bacterial de novo and salvage pathways. Similar to other NAmPRTases, the KVP40 enzyme displayed ATPase activity indicative of energy coupling in the reaction mechanism. The NatV NMNATase activity was measured in a coupled reaction system demonstrating NAD + biosynthesis from nicotinamide, phosphoribosyl pyrophosphate, and ATP. The NatV Nudix hydrolase domain was also shown to be active, with preferred substrates of ADP-ribose, NAD + , and NADH. Expression analysis using reverse transcription-quantitative PCR (qRT-PCR) and enzyme assays of infected Vibrio parahaemolyticus cells demonstrated nadV and natV transcription during the early and delayed-early periods of infection when other KVP40 genes of nucleotide precursor metabolism are expressed. The distribution and phylogeny of NadV and NatV proteins among several large double-stranded DNA (dsDNA) myophages, and also those from some very large siphophages, suggest broad relevance of pyridine nucleotide scavenging in virus-infected cells. NAD + biosynthesis presents another important metabolic resource control point by large, rapidly replicating dsDNA bacteriophages. IMPORTANCE T4-type bacteriophages enhance DNA precursor synthesis through reductive reactions that use NADH/NADPH as the electron donor and NAD

Hanford Site Infrastructure Plan

International Nuclear Information System (INIS)

1990-01-01

The Hanford Site Infrastructure Plan (HIP) has been prepared as an overview of the facilities, utilities, systems, and services that support all activities on the Hanford Site. Its purpose is three-fold: to examine in detail the existing condition of the Hanford Site's aging utility systems, transportation systems, Site services and general-purpose facilities; to evaluate the ability of these systems to meet present and forecasted Site missions; to identify maintenance and upgrade projects necessary to ensure continued safe and cost-effective support to Hanford Site programs well into the twenty-first century. The HIP is intended to be a dynamic document that will be updated accordingly as Site activities, conditions, and requirements change. 35 figs., 25 tabs

Review of Hanford international activities

International Nuclear Information System (INIS)

Panther, D.G.

1993-01-01

Hanford initiated a review of international activities to collect, review, and summarize information on international environmental restoration and waste management initiatives considered for use at Hanford. This effort focused on Hanford activities and accomplishments, especially international technical exchanges and/or the implementation of foreign-developed technologies

Decommissioning planning and the assessment of alternatives for the Hanford production reactors

International Nuclear Information System (INIS)

Miller, C.E. Jr.; Potter, R.F.

1985-01-01

Several years ago, the US Department of Energy began assessing alternatives and planning the decommissioning of eight shut-down plutonium production reactors located on the DOE Hanford Site in Washington State. The first of these graphite-moderated, water-cooled, reactors was built and started up in 1944 as part of the World War II Manhattan Project. The last of them started up in 1955. The eight reactors each operated for 12 to 24 years, with all eight operating simultaneously for about 10 years. In the 1960's, production needs declined and the reactors were one-by-one permanently shut down, the last of them in 1971. (A ninth Hanford production reactor, N Reactor, was started up in 1963; it is still operating and is not within the scope of the decommissioning planning and alternatives assessment work reported in this paper). This paper provides an overview description of the decommissioning plan for the eight shut-down Hanford production reactors and their associated fuel storage basins. Included are descriptions of the decommissioning alternatives considered for the facilities, along with discussions of National Environmental Policy Act (NEPA) process activities applicable to the Hanford decommissioning work. The criteria used in assessing decommissioning alternatives and the assumptions used in the decommissioning planning are identified. 4 refs., 8 figs., 3 tabs

Final Hanford Comprehensive Land-Use Plan Environmental Impact Statement, Hanford Site, Richland, Washington

Energy Technology Data Exchange (ETDEWEB)

N/A

1999-10-01

This Final ''Hanford Comprehensive Land-Use Plan Environmental Impact Statement'' (HCP EIS) is being used by the Department of Energy (DOE) and its nine cooperating and consulting agencies to develop a comprehensive land-use plan (CLUP) for the Hanford Site. The DOE will use the Final HCP EIS as a basis for a Record of Decision (ROD) on a CLUP for the Hanford Site. While development of the CLUP will be complete with release of the HCP EIS ROD, full implementation of the CLUP is expected to take at least 50 years. Implementation of the CLUP would begin a more detailed planning process for land-use and facility-use decisions at the Hanford Site. The DOE would use the CLUP to screen proposals. Eventually, management of Hanford Site areas would move toward the CLUP land-use goals. This CLUP process could take more than 50 years to fully achieve the land-use goals.

Criteria Document for B-plant's Surveillance and Maintenance Phase Safety Basis Document

International Nuclear Information System (INIS)

SCHWEHR, B.A.

1999-01-01

This document is required by the Project Hanford Managing Contractor (PHMC) procedure, HNF-PRO-705, Safety Basis Planning, Documentation, Review, and Approval. This document specifies the criteria that shall be in the B Plant surveillance and maintenance phase safety basis in order to obtain approval of the DOE-RL. This CD describes the criteria to be addressed in the S and M Phase safety basis for the deactivated Waste Fractionization Facility (B Plant) on the Hanford Site in Washington state. This criteria document describes: the document type and format that will be used for the S and M Phase safety basis, the requirements documents that will be invoked for the document development, the deactivated condition of the B Plant facility, and the scope of issues to be addressed in the S and M Phase safety basis document

NAD(H) and NADP(H) Redox Couples and Cellular Energy Metabolism.

Science.gov (United States)

Xiao, Wusheng; Wang, Rui-Sheng; Handy, Diane E; Loscalzo, Joseph

2018-01-20

The nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) and NADP + /reduced NADP + (NADPH) redox couples are essential for maintaining cellular redox homeostasis and for modulating numerous biological events, including cellular metabolism. Deficiency or imbalance of these two redox couples has been associated with many pathological disorders. Recent Advances: Newly identified biosynthetic enzymes and newly developed genetically encoded biosensors enable us to understand better how cells maintain compartmentalized NAD(H) and NADP(H) pools. The concept of redox stress (oxidative and reductive stress) reflected by changes in NAD(H)/NADP(H) has increasingly gained attention. The emerging roles of NAD + -consuming proteins in regulating cellular redox and metabolic homeostasis are active research topics. The biosynthesis and distribution of cellular NAD(H) and NADP(H) are highly compartmentalized. It is critical to understand how cells maintain the steady levels of these redox couple pools to ensure their normal functions and simultaneously avoid inducing redox stress. In addition, it is essential to understand how NAD(H)- and NADP(H)-utilizing enzymes interact with other signaling pathways, such as those regulated by hypoxia-inducible factor, to maintain cellular redox homeostasis and energy metabolism. Additional studies are needed to investigate the inter-relationships among compartmentalized NAD(H)/NADP(H) pools and how these two dinucleotide redox couples collaboratively regulate cellular redox states and cellular metabolism under normal and pathological conditions. Furthermore, recent studies suggest the utility of using pharmacological interventions or nutrient-based bioactive NAD + precursors as therapeutic interventions for metabolic diseases. Thus, a better understanding of the cellular functions of NAD(H) and NADP(H) may facilitate efforts to address a host of pathological disorders effectively. Antioxid. Redox Signal. 28, 251-272.

Hanford Radiological Protection Support Services Annual Report for 1999

Energy Technology Data Exchange (ETDEWEB)

TP Lynch; DE Bihl; ML Johnson; MA MacLellan; RK Piper

2000-05-19

During calendar year (CY) 1999, the Pacific Northwest National Laboratory (PNNL) performed its customary radiological protection support services in support of the U.S. Department of Energy (DOE) Richland Operations Office (RL) and the Hanford contractors. These services included: (1) external dosimetry, (2) internal dosimetry, (3) in vivo measurements, (4) radiological records, (5) instrument calibration and evaluation, and (6) calibration of radiation sources traceable to the National Institute of Standards and Technology (NIST). The services were provided under a number of programs as summarized here. Along with providing site-wide nuclear accident and environmental dosimetry capabilities, the Hanford External Dosimetry Program (HEDP) supports Hanford radiation protection programs by providing external radiation monitoring capabilities for all Hanford workers and visitors to help ensure their health and safety. Processing volumes decreased in CY 1999 relative to prior years for all types of dosimeters, with an overall decrease of 19%. During 1999, the HEDP passed the National Voluntary Laboratory Accreditation Program (NVLAP) performance testing criteria in 15 different categories. HEDP computers and processors were tested and upgraded to become Year 2000 (Y2K) compliant. Several changes and improvements were made to enhance the interpretation of dosimeter results. The Hanford Internal Dosimetry Program (HIDP) provides for the assessment and documentation of occupational dose from intakes of radionuclides at the Hanford Site. Performance problems carried over from CY 1998 continued to plague the in vitro bioassay contractor. A new contract was awarded for the in vitro bioassay program. A new computer system was put into routine operation by the in vivo bioassay program. Several changes to HIDP protocols were made that were related to bioassay grace periods, using field data to characterize the amount of alpha activity present and using a new default particle

Hanford Radiological Protection Support Services Annual Report for 1999

International Nuclear Information System (INIS)

TP Lynch; DE Bihl; ML Johnson; MA MacLellan; RK Piper

2000-01-01

During calendar year (CY) 1999, the Pacific Northwest National Laboratory (PNNL) performed its customary radiological protection support services in support of the U.S. Department of Energy (DOE) Richland Operations Office (RL) and the Hanford contractors. These services included: (1) external dosimetry, (2) internal dosimetry, (3) in vivo measurements, (4) radiological records, (5) instrument calibration and evaluation, and (6) calibration of radiation sources traceable to the National Institute of Standards and Technology (NIST). The services were provided under a number of programs as summarized here. Along with providing site-wide nuclear accident and environmental dosimetry capabilities, the Hanford External Dosimetry Program (HEDP) supports Hanford radiation protection programs by providing external radiation monitoring capabilities for all Hanford workers and visitors to help ensure their health and safety. Processing volumes decreased in CY 1999 relative to prior years for all types of dosimeters, with an overall decrease of 19%. During 1999, the HEDP passed the National Voluntary Laboratory Accreditation Program (NVLAP) performance testing criteria in 15 different categories. HEDP computers and processors were tested and upgraded to become Year 2000 (Y2K) compliant. Several changes and improvements were made to enhance the interpretation of dosimeter results. The Hanford Internal Dosimetry Program (HIDP) provides for the assessment and documentation of occupational dose from intakes of radionuclides at the Hanford Site. Performance problems carried over from CY 1998 continued to plague the in vitro bioassay contractor. A new contract was awarded for the in vitro bioassay program. A new computer system was put into routine operation by the in vivo bioassay program. Several changes to HIDP protocols were made that were related to bioassay grace periods, using field data to characterize the amount of alpha activity present and using a new default particle

The Leishmania nicotinamidase is essential for NAD+ production and parasite proliferation.

Science.gov (United States)

Gazanion, E; Garcia, D; Silvestre, R; Gérard, C; Guichou, J F; Labesse, G; Seveno, M; Cordeiro-Da-Silva, A; Ouaissi, A; Sereno, D; Vergnes, B

2011-10-01

NAD+ is a central cofactor that plays important roles in cellular metabolism and energy production in all living cells. Genomics-based reconstruction of NAD+ metabolism revealed that Leishmania protozoan parasites are NAD+ auxotrophs. Consequently, these parasites require assimilating NAD+ precursors (nicotinamide, nicotinic acid, nicotinamide riboside) from their host environment to synthesize NAD+ by a salvage pathway. Nicotinamidase is a key enzyme of this salvage pathway that catalyses conversion of nicotinamide (NAm) to nicotinic acid (Na), and that is absent in higher eukaryotes. We present here the biochemical and functional characterizations of the Leishmania infantum nicotinamidase (LiPNC1). Generation of Lipnc1 null mutants leads to a decrease in NAD+ content, associated with a metabolic shutdown-like phenotype with an extensive lag phase of growth. Both phenotypes could be rescued by an add-back construct or by addition of exogenous Na. In addition, Lipnc1 null mutants were unable to establish a sustained infection in a murine experimental model. Altogether, these results illustrate that NAD+ homeostasis is a fundamental component of Leishmania biology and virulence, and that NAm constitutes its main NAD+ source in the mammalian host. The crystal structure of LiPNC1 we solved allows now the design of rational inhibitors against this new promising therapeutic target. © 2011 Blackwell Publishing Ltd.

NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In Mice.

Science.gov (United States)

Lin, Jonathan B; Kubota, Shunsuke; Ban, Norimitsu; Yoshida, Mitsukuni; Santeford, Andrea; Sene, Abdoulaye; Nakamura, Rei; Zapata, Nicole; Kubota, Miyuki; Tsubota, Kazuo; Yoshino, Jun; Imai, Shin-Ichiro; Apte, Rajendra S

2016-09-27

Photoreceptor death is the endpoint of many blinding diseases. Identifying unifying pathogenic mechanisms in these diseases may offer global approaches for facilitating photoreceptor survival. We found that rod or cone photoreceptor-specific deletion of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the major NAD(+) biosynthetic pathway beginning with nicotinamide, caused retinal degeneration. In both cases, we could rescue vision with nicotinamide mononucleotide (NMN). Significantly, retinal NAD(+) deficiency was an early feature of multiple mouse models of retinal dysfunction, including light-induced degeneration, streptozotocin-induced diabetic retinopathy, and age-associated dysfunction. Mechanistically, NAD(+) deficiency caused metabolic dysfunction and consequent photoreceptor death. We further demonstrate that the NAD(+)-dependent mitochondrial deacylases SIRT3 and SIRT5 play important roles in retinal homeostasis and that NAD(+) deficiency causes SIRT3 dysfunction. These findings demonstrate that NAD(+) biosynthesis is essential for vision, provide a foundation for future work to further clarify the mechanisms involved, and identify a unifying therapeutic target for diverse blinding diseases. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Loss of NAD Homeostasis Leads to Progressive and Reversible Degeneration of Skeletal Muscle.

Science.gov (United States)

Frederick, David W; Loro, Emanuele; Liu, Ling; Davila, Antonio; Chellappa, Karthikeyani; Silverman, Ian M; Quinn, William J; Gosai, Sager J; Tichy, Elisia D; Davis, James G; Mourkioti, Foteini; Gregory, Brian D; Dellinger, Ryan W; Redpath, Philip; Migaud, Marie E; Nakamaru-Ogiso, Eiko; Rabinowitz, Joshua D; Khurana, Tejvir S; Baur, Joseph A

2016-08-09

NAD is an obligate co-factor for the catabolism of metabolic fuels in all cell types. However, the availability of NAD in several tissues can become limited during genotoxic stress and the course of natural aging. The point at which NAD restriction imposes functional limitations on tissue physiology remains unknown. We examined this question in murine skeletal muscle by specifically depleting Nampt, an essential enzyme in the NAD salvage pathway. Knockout mice exhibited a dramatic 85% decline in intramuscular NAD content, accompanied by fiber degeneration and progressive loss of both muscle strength and treadmill endurance. Administration of the NAD precursor nicotinamide riboside rapidly ameliorated functional deficits and restored muscle mass despite having only a modest effect on the intramuscular NAD pool. Additionally, lifelong overexpression of Nampt preserved muscle NAD levels and exercise capacity in aged mice, supporting a critical role for tissue-autonomous NAD homeostasis in maintaining muscle mass and function. Copyright © 2016 Elsevier Inc. All rights reserved.

Strontium-90 at the Hanford Site and its ecological implications

International Nuclear Information System (INIS)

RE Peterson; TM Poston

2000-01-01

Strontium-90, a radioactive contaminant from historical operations at the U.S. Department of Energy (DOE) Hanford Site, enters the Columbia River at several locations associated with former plutonium production reactors at the Site. Strontium-90 is of concern to humans and the environment because of its moderately long half-life (29.1 years), its potential for concentrating in bone tissue, and its relatively high energy of beta decay. Although strontium-90 in the environment is not a new issue for the Hanford Site, recent studies of near-river vegetation along the shoreline near the 100 Areas raised public concern about the possibility of strontium-90-contaminated groundwater reaching the riverbed and fall chinook salmon redds. To address these concerns, DOE asked Pacific Northwest National Laboratory (PNNL) to prepare this report on strontium-90, its distribution in groundwater, how and where it enters the river, and its potential ecological impacts, particularly with respect to fall chinook salmon. The purpose of the report is to characterize groundwater contaminants in the near-shore environment and to assess the potential for ecological impact using salmon embryos, one of the most sensitive ecological indicators for aquatic organisms. Section 2.0 of the report provides background information on strontium-90 at the Hanford Site related to historical operations. Public access to information on strontium-90 also is described. Section 3.0 focuses on key issues associated with strontium-90 contamination in groundwater that discharges in the Hanford Reach. The occurrence and distribution of fall chinook salmon redds in the Hanford Reach and characteristics of salmon spawning are described in Section 4.0. Section 5.0 describes the regulatory standards and criteria used to set action levels for strontium-90. Recommendations for initiating additional monitoring and remedial action associated with strontium-90 contamination at the Hanford Site are presented in Section 6

Strontium-90 at the Hanford Site and its ecological implications

Energy Technology Data Exchange (ETDEWEB)

RE Peterson; TM Poston

2000-05-22

Strontium-90, a radioactive contaminant from historical operations at the U.S. Department of Energy (DOE) Hanford Site, enters the Columbia River at several locations associated with former plutonium production reactors at the Site. Strontium-90 is of concern to humans and the environment because of its moderately long half-life (29.1 years), its potential for concentrating in bone tissue, and its relatively high energy of beta decay. Although strontium-90 in the environment is not a new issue for the Hanford Site, recent studies of near-river vegetation along the shoreline near the 100 Areas raised public concern about the possibility of strontium-90-contaminated groundwater reaching the riverbed and fall chinook salmon redds. To address these concerns, DOE asked Pacific Northwest National Laboratory (PNNL) to prepare this report on strontium-90, its distribution in groundwater, how and where it enters the river, and its potential ecological impacts, particularly with respect to fall chinook salmon. The purpose of the report is to characterize groundwater contaminants in the near-shore environment and to assess the potential for ecological impact using salmon embryos, one of the most sensitive ecological indicators for aquatic organisms. Section 2.0 of the report provides background information on strontium-90 at the Hanford Site related to historical operations. Public access to information on strontium-90 also is described. Section 3.0 focuses on key issues associated with strontium-90 contamination in groundwater that discharges in the Hanford Reach. The occurrence and distribution of fall chinook salmon redds in the Hanford Reach and characteristics of salmon spawning are described in Section 4.0. Section 5.0 describes the regulatory standards and criteria used to set action levels for strontium-90. Recommendations for initiating additional monitoring and remedial action associated with strontium-90 contamination at the Hanford Site are presented in Section 6

Hanford Emergency Response Plan

International Nuclear Information System (INIS)

Wagoner, J.D.

1994-04-01

The Hanford Emergency Response Plan for the US Department of Energy (DOE), Richland Operations Office (RL), incorporates into one document an overview of the emergency management program for the Hanford Site. The program has been developed in accordance with DOE orders, and state and federal regulations to protect worker and public health and safety and the environment in the event of an emergency at or affecting the Hanford Site. This plan provides a description of how the Hanford Site will implement the provisions of DOE 5500 series and other applicable Orders in terms of overall policies and concept of operations. It should be used as the basis, along with DOE Orders, for the development of specific contractor and RL implementing procedures

Hanford Emergency Response Plan

Energy Technology Data Exchange (ETDEWEB)

Wagoner, J.D.

1994-04-01

The Hanford Emergency Response Plan for the US Department of Energy (DOE), Richland Operations Office (RL), incorporates into one document an overview of the emergency management program for the Hanford Site. The program has been developed in accordance with DOE orders, and state and federal regulations to protect worker and public health and safety and the environment in the event of an emergency at or affecting the Hanford Site. This plan provides a description of how the Hanford Site will implement the provisions of DOE 5500 series and other applicable Orders in terms of overall policies and concept of operations. It should be used as the basis, along with DOE Orders, for the development of specific contractor and RL implementing procedures.

The reported human NADsyn2 is ammonia-dependent NAD synthetase from a pseudomonad.

Science.gov (United States)

Bieganowski, Pawel; Brenner, Charles

2003-08-29

Nicotinamide-adenine dinucleotide (NAD+) synthetases catalyze the last step in NAD+ metabolism in the de novo, import, and salvage pathways that originate from tryptophan (or aspartic acid), nicotinic acid, and nicotinamide, respectively, and converge on nicotinic acid mononucleotide. NAD+ synthetase converts nicotinic acid adenine dinucleotide to NAD+ via an adenylylated intermediate. All of the known eukaryotic NAD+ synthetases are glutamine-dependent, hydrolyzing glutamine to glutamic acid to provide the attacking ammonia. In the prokaryotic world, some NAD+ synthetases are glutamine-dependent, whereas others can only use ammonia. Earlier, we noted a perfect correlation between presence of a domain related to nitrilase and glutamine dependence and then proved in the accompanying paper (Bieganowski, P., Pace, H. C., and Brenner, C. (2003) J. Biol. Chem. 278, 33049-33055) that the nitrilase-related domain is an essential, obligate intramolecular, thiol-dependent glutamine amidotransferase in the yeast NAD+ synthetase, Qns1. Independently, human NAD+ synthetase was cloned and shown to depend on Cys-175 for glutamine-dependent but not ammonia-dependent NAD+ synthetase activity. Additionally, it was claimed that a 275 amino acid open reading frame putatively amplified from human glioma cell line LN229 encodes a human ammonia-dependent NAD+ synthetase and this was speculated largely to mediate NAD+ synthesis in human muscle tissues. Here we establish that the so-called NADsyn2 is simply ammonia-dependent NAD+ synthetase from Pseudomonas, which is encoded on an operon with nicotinic acid phosphoribosyltransferase and, in some Pseudomonads, with nicotinamidase.

Independent engineering review of the Hanford Waste Vitrification System

International Nuclear Information System (INIS)

1991-10-01

The Hanford Waste Vitrification Plant (HWVP) was initiated in June 1987. The HWVP is an essential element of the plan to end present interim storage practices for defense wastes and to provide for permanent disposal. The project start was justified, in part, on efficient technology and design information transfer from the prototype Defense Waste Processing Facility (DWPF). Development of other serial Hanford Waste Vitrification System (HWVS) elements, such as the waste retrieval system for the double-shell tanks (DSTs), and the pretreatment system to reduce the waste volume converted into glass, also was required to accomplish permanent waste disposal. In July 1991, at the time of this review, the HWVP was in the Title 2 design phase. The objective of this technical assessment is to determine whether the status of the technology development and engineering practice is sufficient to provide reasonable assurance that the HWVP and the balance of the HWVS system will operate in an efficient and cost-effective manner. The criteria used to facilitate a judgment of potential successful operation are: vitrification of high-level radioactive waste from specified DSTs on a reasonably continuous basis; and glass produced with physical and chemical properties formally acknowledge as being acceptable for disposal in a repository for high-level radioactive waste. The criteria were proposed specifically for the Independent Engineering Review to focus that assessment effort. They are not represented as the criteria by which the Department will judge the prudence of the Project. 78 refs., 10 figs., 12 tabs

Independent engineering review of the Hanford Waste Vitrification System

Energy Technology Data Exchange (ETDEWEB)

1991-10-01

The Hanford Waste Vitrification Plant (HWVP) was initiated in June 1987. The HWVP is an essential element of the plan to end present interim storage practices for defense wastes and to provide for permanent disposal. The project start was justified, in part, on efficient technology and design information transfer from the prototype Defense Waste Processing Facility (DWPF). Development of other serial Hanford Waste Vitrification System (HWVS) elements, such as the waste retrieval system for the double-shell tanks (DSTs), and the pretreatment system to reduce the waste volume converted into glass, also was required to accomplish permanent waste disposal. In July 1991, at the time of this review, the HWVP was in the Title 2 design phase. The objective of this technical assessment is to determine whether the status of the technology development and engineering practice is sufficient to provide reasonable assurance that the HWVP and the balance of the HWVS system will operate in an efficient and cost-effective manner. The criteria used to facilitate a judgment of potential successful operation are: vitrification of high-level radioactive waste from specified DSTs on a reasonably continuous basis; and glass produced with physical and chemical properties formally acknowledge as being acceptable for disposal in a repository for high-level radioactive waste. The criteria were proposed specifically for the Independent Engineering Review to focus that assessment effort. They are not represented as the criteria by which the Department will judge the prudence of the Project. 78 refs., 10 figs., 12 tabs.

Hanford Integrated Planning Process: 1993 Hanford Site-specific science and technology plan

International Nuclear Information System (INIS)

1993-12-01

This document is the FY 1993 report on Hanford Site-specific science and technology (S ampersand T) needs for cleanup of the Site as developed via the Hanford Integrated Planning Process (HIPP). It identifies cleanup problems that lack demonstrated technology solutions and technologies that require additional development. Recommendations are provided regarding allocation of funding to address Hanford's highest-priority technology improvement needs, technology development needs, and scientific research needs, all compiled from a Sitewide perspective. In the past, the S ampersand T agenda for Hanford Site cleanup was sometimes driven by scientists and technologists, with minimal input from the ''problem owners'' (i.e., Westinghouse Hanford Company [WHC] staff who are responsible for cleanup activities). At other times, the problem-owners made decisions to proceed with cleanup without adequate scientific and technological inputs. Under both of these scenarios, there was no significant stakeholder involvement in the decision-making process. One of the key objectives of HIPP is to develop an understanding of the integrated S ampersand T requirements to support the cleanup mission, (a) as defined by the needs of the problem owners, the values of the stakeholders, and the technology development expertise that exists at Hanford and elsewhere. This requires a periodic, systematic assessment of these needs and values to appropriately define a comprehensive technology development program and a complementary scientific research program. Basic to our success is a methodology that is defensible from a technical perspective and acceptable to the stakeholders

Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum.

Directory of Open Access Journals (Sweden)

Jessica K O'Hara

Full Text Available Nicotinamide adenine dinucleotide (NAD+ is an essential metabolite utilized as a redox cofactor and enzyme substrate in numerous cellular processes. Elevated NAD+ levels have been observed in red blood cells infected with the malaria parasite Plasmodium falciparum, but little is known regarding how the parasite generates NAD+. Here, we employed a mass spectrometry-based metabolomic approach to confirm that P. falciparum lacks the ability to synthesize NAD+ de novo and is reliant on the uptake of exogenous niacin. We characterized several enzymes in the NAD+ pathway and demonstrate cytoplasmic localization for all except the parasite nicotinamidase, which concentrates in the nucleus. One of these enzymes, the P. falciparum nicotinate mononucleotide adenylyltransferase (PfNMNAT, is essential for NAD+ metabolism and is highly diverged from the human homolog, but genetically similar to bacterial NMNATs. Our results demonstrate the enzymatic activity of PfNMNAT in vitro and demonstrate its ability to genetically complement the closely related Escherichia coli NMNAT. Due to the similarity of PfNMNAT to the bacterial enzyme, we tested a panel of previously identified bacterial NMNAT inhibitors and synthesized and screened twenty new derivatives, which demonstrate a range of potency against live parasite culture. These results highlight the importance of the parasite NAD+ metabolic pathway and provide both novel therapeutic targets and promising lead antimalarial compounds.

Normalization of NAD+ Redox Balance as a Therapy for Heart Failure.

Science.gov (United States)

Lee, Chi Fung; Chavez, Juan D; Garcia-Menendez, Lorena; Choi, Yongseon; Roe, Nathan D; Chiao, Ying Ann; Edgar, John S; Goo, Young Ah; Goodlett, David R; Bruce, James E; Tian, Rong

2016-09-20

Impairments of mitochondrial function in the heart are linked intricately to the development of heart failure, but there is no therapy for mitochondrial dysfunction. We assessed the reduced/oxidized ratio of nicotinamide adenine dinucleotide (NADH/NAD(+) ratio) and protein acetylation in the failing heart. Proteome and acetylome analyses were followed by docking calculation, mutagenesis, and mitochondrial calcium uptake assays to determine the functional role of specific acetylation sites. The therapeutic effects of normalizing mitochondrial protein acetylation by expanding the NAD(+) pool also were tested. Increased NADH/NAD(+) and protein hyperacetylation, previously observed in genetic models of defective mitochondrial function, also are present in human failing hearts as well as in mouse hearts with pathologic hypertrophy. Elevation of NAD(+) levels by stimulating the NAD(+) salvage pathway suppressed mitochondrial protein hyperacetylation and cardiac hypertrophy, and improved cardiac function in responses to stresses. Acetylome analysis identified a subpopulation of mitochondrial proteins that was sensitive to changes in the NADH/NAD(+) ratio. Hyperacetylation of mitochondrial malate-aspartate shuttle proteins impaired the transport and oxidation of cytosolic NADH in the mitochondria, resulting in altered cytosolic redox state and energy deficiency. Furthermore, acetylation of oligomycin-sensitive conferring protein at lysine-70 in adenosine triphosphate synthase complex promoted its interaction with cyclophilin D, and sensitized the opening of mitochondrial permeability transition pore. Both could be alleviated by normalizing the NAD(+) redox balance either genetically or pharmacologically. We show that mitochondrial protein hyperacetylation due to NAD(+) redox imbalance contributes to the pathologic remodeling of the heart via 2 distinct mechanisms. Our preclinical data demonstrate a clear benefit of normalizing NADH/NAD(+) imbalance in the failing hearts

Hairpin stabilized fluorescent silver nanoclusters for quantitative detection of NAD+ and monitoring NAD+/NADH based enzymatic reactions.

Science.gov (United States)

Jain, Priyamvada; Chakma, Babina; Patra, Sanjukta; Goswami, Pranab

2017-03-01

A set of 90 mer long ssDNA candidates, with different degrees of cytosine (C-levels) (% and clusters) was analyzed for their function as suitable Ag-nanocluster (AgNC) nucleation scaffolds. The sequence (P4) with highest C-level (42.2%) emerged as the only candidate supporting the nucleation process as evident from its intense fluorescence peak at λ 660 nm . Shorter DNA subsets derived from P4 with only stable hairpin structures could support the AgNC formation. The secondary hairpin structures were confirmed by PAGE, and CD studies. The number of base pairs in the stem region also contributes to the stability of the hairpins. A shorter 29 mer sequence (Sub 3) (ΔG = -1.3 kcal/mol) with 3-bp in the stem of a 7-mer loop conferred highly stable AgNC. NAD + strongly quenched the fluorescence of Sub 3-AgNC in a concentration dependent manner. Time resolved photoluminescence studies revealed the quenching involves a combined static and dynamic interaction where the binding constant and number of binding sites for NAD + were 0.201 L mol -1 and 3.6, respectively. A dynamic NAD + detection range of 50-500 μM with a limit of detection of 22.3 μM was discerned. The NAD + mediated quenching of AgNC was not interfered by NADH, NADP + , monovalent and divalent ions, or serum samples. The method was also used to follow alcohol dehydrogenase and lactate dehydrogenase catalyzed physiological reactions in a turn-on and turn-off assay, respectively. The proposed method with ssDNA-AgNC could therefore be extended to monitor other NAD + /NADH based enzyme catalyzed reactions in a turn-on/turn-off approach. Copyright © 2016 Elsevier B.V. All rights reserved.

Increased Rate of NAD Metabolism Shortens Plant Longevity by Accelerating Developmental Senescence in Arabidopsis.

Science.gov (United States)

Hashida, Shin-Nosuke; Itami, Taketo; Takahara, Kentaro; Hirabayashi, Takayuki; Uchimiya, Hirofumi; Kawai-Yamada, Maki

2016-11-01

NAD is a well-known co-enzyme that mediates hundreds of redox reactions and is the basis of various processes regulating cell responses to different environmental and developmental cues. The regulatory mechanism that determines the amount of cellular NAD and the rate of NAD metabolism remains unclear. We created Arabidopsis thaliana plants overexpressing the NAD synthase (NADS) gene that participates in the final step of NAD biosynthesis. NADS overexpression enhanced the activity of NAD biosynthesis but not the amounts of NAD + , NADH, NADP + or NADPH. However, the amounts of some intermediates were elevated, suggesting that NAD metabolism increased. The NAD redox state was greatly facilitated by an imbalance between NAD generation and degradation in response to bolting. Metabolite profiling and transcriptional analysis revealed that the drastic modulation of NAD redox homeostasis increased tricarboxylic acid flux, causing the ectopic generation of reactive oxygen species. Vascular bundles suffered from oxidative stress, leading to a malfunction in amino acid and organic acid transportation that caused early wilting of the flower stalk and shortened plant longevity, probably due to malnutrition. We concluded that the mechanism regulating the balance between NAD synthesis and degradation is important in the systemic plant response to developmental cues during the growth-phase transition. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

One-electron transfer reactions of the couple NAD./NADH

International Nuclear Information System (INIS)

Grodkowski, J.; Neta, P.; Carlson, B.W.; Miller, L.

1983-01-01

One-electron transfer reactions involving nicotinamide-adenine dinucleotide in its oxidized and reducd forms (NAD./NADH) were studied by pulse radiolysis in aqueous solutions. One-electron oxidation of NADH by various phenoxyl radicals and phenothiazine cation radicals was found to take place with rate constants in the range of 10 5 to 10 8 M -1 s -1 , depending on the redox potential of the oxidizing species. In all cases, NAD. is formed quantitatively with no indication for the existence of the protonated form (NADH + .). The spectrum of NAD., as well as the rates of oxidation of NADH by phenoxyl and by (chlorpromazine) + . were independent of pH between pH 4.5 and 13.5. Reaction of deuterated NADH indicated only a small kinetic isotope effect. All these findings point to an electron transfer mechanism. On the other hand, attempts to observe the reverse electron transfer, i.e., one-electron reduction of NAD. to NADH by radicals such as semiquinones, showed that k was less than 10 4 to 10 5 M -1 s -1 , so that it was unobservable. Consequently, it was not possible to achieve equilibrium conditions which would have permitted the direct measurement of the redox potential for NAD./NADH. One-electron reduction of NAD. appears to be an unlikely process. 1 table

Identification of a repressor gene involved in the regulation of NAD de novo biosynthesis in Salmonella typhimurium.

OpenAIRE

Zhu, N; Olivera, B M; Roth, J R

1988-01-01

Mutations at the nadI locus affect expression of the first two genes of NAD synthesis, nadA and nadB, which are unlinked. Genetic data imply that the regulatory effects of nadI mutations are not due to indirect consequences of physiological alterations. Two types of mutations map in the nadI region. Common null mutations (nadI) show constitutive high-level expression of the nadB and nadA genes. Rare nadIs mutations cause constitutive low-level expression of nadB and nadA. Some nadIs mutations...

Materials selection for process equipment in the Hanford waste vitrification plant

Energy Technology Data Exchange (ETDEWEB)

Elmore, M R; Jensen, G A

1991-07-01

The Hanford Waste Vitrification Plant (HWVP) is being designed to vitrify defense liquid high-level wastes and transuranic wastes stored at Hanford. The HWVP Functional Design Criteria (FDC) requires that materials used for fabrication of remote process equipment and piping in the facility be compatible with the expected waste stream compositions and process conditions. To satisfy FDC requirements, corrosion-resistant materials have been evaluated under simulated HWVP-specific conditions and recommendations have been made for HWVP applications. The materials recommendations provide to the project architect/engineer the best available corrosion rate information for the materials under the expected HWVP process conditions. Existing data and sound engineering judgement must be used and a solid technical basis must be developed to define an approach to selecting suitable construction materials for the HWVP. This report contains the strategy, approach, criteria, and technical basis developed for selecting materials of construction. Based on materials testing specific to HWVP and on related outside testing, this report recommends for constructing specific process equipment and identifies future testing needs to complete verification of the performance of the selected materials. 30 refs., 7 figs., 11 tabs.

NAD+ : A big player in cardiac and skeletal muscle remodeling and aging.

Science.gov (United States)

Chaturvedi, Pankaj; Tyagi, Suresh C

2018-03-01

In the past decade, NAD+ has gained importance for its beneficial effects as antioxidant and anti-aging molecule. A paper in science by Zhang et al. () has described that NAD+ when replenished, ameliorates muscle dystrophy in mice by improving mitochondrial function. NAD+ was also demonstrated by the authors to improve the life span of mice. Cox et al. () demonstrated the cardiac effects of NAD+ which mitigated chronic heart failure via mitochondrial redox state mechanism. Cox et al. () also demonstrated that NAD+ is provided in the drinking water, it improves cardiac relaxation in volume overload model of heart failure. Although NAD+ has a profound anti-aging and anti-oxidant effects, its effect on humans and use as a dietary supplement needs more exploration. © 2017 Wiley Periodicals, Inc.

Nads FSK Modem, LEA 74-2248

International Nuclear Information System (INIS)

Johnson, K.R.

1976-01-01

The Nads FSK Modem is a compact unit designed to operate in conjunction with EIA standard interfacing and the data terminal equipment of the 1200 Baud digital communications network of the Nevada Automated Diagnostics System (NADS). The modem is constructed in a Nuclear Instrumentation Module System (NIMS) module for compatability with the NADS system. The modulator section of the modem accepts serial, digital signals at 1200 Baud which may be either standard TTL levels or bipolar signals meeting either the EIA RS-232C or RS-232B standards. The output of the modulator is a Frequency-Shift Keyed (FSK) signal having frequencies of 2.2 kHz for Mark and 1.2 kHz for Space. The demodulator section accepts the above FSK signal as input, and outputs serial, digital signals at 1200 Baud at either TTL or EIA RS-232C levels. Specifications and operation and calibration instructions are given

The Wahluke (North) Slope of the Hanford Site: History and present challenges

International Nuclear Information System (INIS)

Gerber, M.S.

1996-01-01

The Hanford Site was founded in early 1943 for the top secret government mission of producing plutonium for the world's first atomic weapons. A great deal of land was needed, both to separate various Site facilities from each other, and to provide buffer zones for safety and security purposes. In total, 640 square miles were occupied by the original Hanford Site and its buffer zones. Much of this land had been earmarked for inclusion in the Columbia Basin Irrigation Project (CBP). After World War II ended, a series of national decisions led to a long-term mission for the Hanford Site, and area residents learned that the Site lands they had hoped to farm would be withheld from agricultural production for the foreseeable future. A long set of negotiations commenced between the federal management agency responsible for Hanford (the Atomic Energy Commission -- AEC), and the Bureau of Reclamation (BOR), Department of the Interior that managed the CBP. Some lands were turned back to agriculture, and other compromises made, in the Site's far northern buffer lands known as the Wahluke Slope, during the 1950s. In the mid-1960s, further negotiations were about to allow farming on lands just north of the Columbia River, opposite Hanford's reactors, when studies conducted by the BOR found drainage barriers to irrigation. As a result of these findings, two wildlife refuges were created on that land in 1971. Today, after the Hanford Site plutonium production mission has ended and as Site cleanup goes forward, the possibility of total release of Wahluke Slope lands from the control of the Department of Energy (DOE -- a successor agency to the AEC) is under discussion. Such discussion encompasses not just objective and clearly visible criteria, but it resurrects historical debates about the roles of farming and government presence in the Columbia Basin

Hanford Site technical baseline database. Revision 1

International Nuclear Information System (INIS)

Porter, P.E.

1995-01-01

This report lists the Hanford specific files (Table 1) that make up the Hanford Site Technical Baseline Database. Table 2 includes the delta files that delineate the differences between this revision and revision 0 of the Hanford Site Technical Baseline Database. This information is being managed and maintained on the Hanford RDD-100 System, which uses the capabilities of RDD-100, a systems engineering software system of Ascent Logic Corporation (ALC). This revision of the Hanford Site Technical Baseline Database uses RDD-100 version 3.0.2.2 (see Table 3). Directories reflect those controlled by the Hanford RDD-100 System Administrator. Table 4 provides information regarding the platform. A cassette tape containing the Hanford Site Technical Baseline Database is available

Genetically encoded probes for NAD+/NADH monitoring.

Science.gov (United States)

Bilan, Dmitry S; Belousov, Vsevolod V

2016-11-01

NAD + and NADH participate in many metabolic reactions. The NAD + /NADH ratio is an important parameter reflecting the general metabolic and redox state of different types of cells. For a long time, in situ and in vivo NAD + /NADH monitoring has been hampered by the lack of suitable tools. The recent development of genetically encoded indicators based on fluorescent proteins linked to specific nucleotide-binding domains has already helped to address this monitoring problem. In this review, we will focus on four available indicators: Peredox, Frex family probes, RexYFP and SoNar. Each indicator has advantages and limitations. We will also discuss the most important points that should be considered when selecting a suitable indicator for certain experimental conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

The Hanford Site: An anthology of early histories

Energy Technology Data Exchange (ETDEWEB)

Gerber, M.S.

1993-10-01

This report discusses the following topics: Memories of War: Pearl Harbor and the Genesis of the Hanford Site; safety has always been promoted at the Hanford Site; women have an important place in Hanford Site history; the boom and bust cycle: A 50-year historical overview of the economic impacts of Hanford Site Operations on the Tri-Cities, Washington; Hanford`s early reactors were crucial to the sites`s history; T-Plant made chemical engineering history; the UO{sub 3} plant has a long history of service. PUREX Plant: the Hanford Site`s Historic Workhorse. PUREX Plant Waste Management was a complex challenge; and early Hanford Site codes and jargon.

ChemWaste appeals Hanford permit stance

International Nuclear Information System (INIS)

Anon.

1993-01-01

Chemical Waste Management, Inc. is appealing the Washington State Department of Ecology's decision to suspend its review of the company's proposal to build a hazardous waste incinerator and two mixed waste incinerators at the Hanford Nuclear Site near Richland, Washington. The company wants to build the incinerators on a 200 acre parcel in the DOE reservation that is leased to the State. The State contends the two mixed waste incinerators meet siting criteria, but the hazardous waste unit does not. A compromise may be reached between DOE and Washington state involving the transfer of title to the leased land from DOE to the State

Application of Systems Engineering to U.S. Department of Energy Privatization Project Selection at the Hanford Nuclear Reservation

International Nuclear Information System (INIS)

Layman, John Scott

1999-01-01

The privatization efforts at the U.S. Department of Energy's Hanford Nuclear Reservation have been very successful primarily due to a disciplined process for project selection and execution. Early in the development of Privatization at Hanford, the Department of Energy determined that a disciplined alternatives generation and analysis (AGA) process would furnish the candidate projects with the best probability for success. Many factors had to be considered in the selection of projects. Westinghouse Hanford Company was assigned to develop this process and facilitate the selection of the first round of candidate privatization projects. Team members for the AGA process were assembled from all concerned organizations and skill groups. Among the selection criteria were legal, financial and technical considerations which had to be weighed

Mechanistic Links Between PARP, NAD, and Brain Inflammation After TBI

Science.gov (United States)

2015-10-01

1 AWARD NUMBER: W81XWH-13-2-0091 TITLE: Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI PRINCIPAL INVESTIGATOR...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Mechanistic Links Between PARP, NAD , and Brain Inflammation After TBI 5b. GRANT...efficacy of veliparib and NAD as agents for suppressing inflammation and improving outcomes after traumatic brain injury. The animal models include

Anticancer agent CHS-828 inhibits cellular synthesis of NAD

DEFF Research Database (Denmark)

Olesen, U.H.; Christensen, M.K.; Bjorkling, F.

2008-01-01

Malignant cells display increased demands for energy production and DNA repair. Nicotinamide adenine dinucleotide (NAD) is required for both processes and is also continuously degraded by cellular enzymes. Nicotinamide phosphoribosyltransferase (Nampt) is a crucial factor in the resynthesis of NAD......, and thus in cancer cell survival. Here, we establish the cytotoxic mechanism of action of the small molecule inhibitor CHS-828 to result from impaired synthesis of NAD. Initially, we detected cross-resistance in cells between CHS-828 and a known inhibitor of Nampt, FK866, a compound of a structurally...... different class. We then showed that nicotinamide protects against CHS-828-mediated cytotoxicity. Finally, we observed that treatment with CHS-828 depletes cellular NAD levels in sensitive cancer cells. In conclusion, these results strongly suggest that, like FK866, CHS-828 kills cancer cells by depleting...

Analysis of organic carbon and moisture in Hanford single-shell tank waste

Energy Technology Data Exchange (ETDEWEB)

Toth, J.J.; Heasler, P.G.; Lerchen, M.E.; Hill, J.G.; Whitney, P.D.

1995-05-01

This report documents a revised analysis performed by Pacific Northwest Laboratory involving the organic carbon laboratory measurement data for Hanford single-shell tanks (SSTs) obtained from a review of the laboratory analytical data. This activity has as its objective to provide a best-estimate, including confidence levels, of total organic carbon (TOC) and moisture in each of the 149 SSTs at Hanford. The TOC and moisture information presented in this report is useful as part of the criteria to identify SSTs for additional measurements, or monitoring for the Organic Safety Program. In April 1994, an initial study of the organic carbon in Hanford single-shell tanks was completed at PNL. That study reflected the estimates of TOC based on tank characterizations datasets that were available at the time. Also in that study, estimation of dry basis TOC was based on generalized assumptions pertaining to the moisture of the tank wastes. The new information pertaining to tank moisture and TOC data that has become available from the current study influences the best estimates of TOC in each of the SSTs. This investigation of tank TOC and moisture has resulted in improved estimates based on waste phase: saltcake, sludge, or liquid. This report details the assumptions and methodologies used to develop the estimates of TOC and moisture in each of the 149 SSTs at Hanford.

Analysis of organic carbon and moisture in Hanford single-shell tank waste

International Nuclear Information System (INIS)

Toth, J.J.; Heasler, P.G.; Lerchen, M.E.; Hill, J.G.; Whitney, P.D.

1995-05-01

This report documents a revised analysis performed by Pacific Northwest Laboratory involving the organic carbon laboratory measurement data for Hanford single-shell tanks (SSTs) obtained from a review of the laboratory analytical data. This activity has as its objective to provide a best-estimate, including confidence levels, of total organic carbon (TOC) and moisture in each of the 149 SSTs at Hanford. The TOC and moisture information presented in this report is useful as part of the criteria to identify SSTs for additional measurements, or monitoring for the Organic Safety Program. In April 1994, an initial study of the organic carbon in Hanford single-shell tanks was completed at PNL. That study reflected the estimates of TOC based on tank characterizations datasets that were available at the time. Also in that study, estimation of dry basis TOC was based on generalized assumptions pertaining to the moisture of the tank wastes. The new information pertaining to tank moisture and TOC data that has become available from the current study influences the best estimates of TOC in each of the SSTs. This investigation of tank TOC and moisture has resulted in improved estimates based on waste phase: saltcake, sludge, or liquid. This report details the assumptions and methodologies used to develop the estimates of TOC and moisture in each of the 149 SSTs at Hanford

Hanford well custodians. Revision 1

International Nuclear Information System (INIS)

Schatz, A.L.; Underwood, D.J.

1995-01-01

The Hanford Site Groundwater Protection Management Program recognized the need to integrate monitoring well activities in a centralized manner. A key factor to Hanford Site well integration was the need to clearly identify a responsible party for each of the wells. WHC was asked to identify all wells on site, the program(s) using each well, and the program ultimately responsible for the well. This report lists the custodian and user(s) for each Hanford well and supplies a comprehensive list of all decommissioned and orphaned wells on the Hanford Site. This is the first update to the original report released in December 1993

Modeling of NAD+ analogues in horse liver alcohol dehydrogenase

NARCIS (Netherlands)

Beijer, N.A.; Buck, H.M.; Sluyterman, L.A.A.E.; Meijer, E.M.

1990-01-01

So far, the interactions of nicotinamide adenine dinucleotide (NAD+) derivatives with dehydrogenases are not very well understood. This hampers the introduction of NAD+ analogues with improved characteristics concerning industrial application. We have developed an AMBER molecular mechanics model in

Hanford Site peak gust wind speeds

International Nuclear Information System (INIS)

Ramsdell, J.V.

1998-01-01

Peak gust wind data collected at the Hanford Site since 1945 are analyzed to estimate maximum wind speeds for use in structural design. The results are compared with design wind speeds proposed for the Hanford Site. These comparisons indicate that design wind speeds contained in a January 1998 advisory changing DOE-STD-1020-94 are excessive for the Hanford Site and that the design wind speeds in effect prior to the changes are still appropriate for the Hanford Site

The Peroxisomal NAD Carrier from Arabidopsis Imports NAD in Exchange with AMP

NARCIS (Netherlands)

van Roermund, Carlo W. T.; Schroers, Martin G.; Wiese, Jan; Facchinelli, Fabio; Kurz, Samantha; Wilkinson, Sabrina; Charton, Lennart; Wanders, Ronald J. A.; Waterham, Hans R.; Weber, Andreas P. M.; Link, Nicole

2016-01-01

Cofactors such as NAD, AMP, and Coenzyme A (CoA) are essential for a diverse set of reactions and pathways in the cell. Specific carrier proteins are required to distribute these cofactors to different cell compartments, including peroxisomes. We previously identified a peroxisomal transport protein

Assessment of candidate sites for disposal of treated effluents at the Hanford Site, Washington

International Nuclear Information System (INIS)

Davis, J.D.

1992-01-01

A rigidly defined evaluation process was used to recommend a preferred location to dispose of treated effluents from facilities in the 200 Areas of the US Department of Energy's Hanford Site in Washington State. First, siting constraints were defined based on functional design considerations and siting guidelines. Then, criteria for selecting a preferred site from among several candidates were identified and their relative importance defined. Finally, the weighted criteria were applied and a site was selected for detailed characterization by subsurface investigations

Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?

Directory of Open Access Journals (Sweden)

Marwa Elamin

2017-11-01

Full Text Available The ketogenic diet’s (KD anticonvulsant effects have been well-documented for nearly a century, including in randomized controlled trials. Some patients become seizure-free and some remain so after diet cessation. Many recent studies have explored its expanded therapeutic potential in diverse neurological disorders, yet no mechanism(s of action have been established. The diet’s high fat, low carbohydrate composition reduces glucose utilization and promotes the production of ketone bodies. Ketone bodies are a more efficient energy source than glucose and improve mitochondrial function and biogenesis. Cellular energy production depends on the metabolic coenzyme nicotinamide adenine dinucleotide (NAD, a marker for mitochondrial and cellular health. Furthermore, NAD activates downstream signaling pathways (such as the sirtuin enzymes associated with major benefits such as longevity and reduced inflammation; thus, increasing NAD is a coveted therapeutic endpoint. Based on differential NAD+ utilization during glucose- vs. ketone body-based acetyl-CoA generation for entry into the tricarboxylic cycle, we propose that a KD will increase the NAD+/NADH ratio. When rats were fed ad libitum KD, significant increases in hippocampal NAD+/NADH ratio and blood ketone bodies were detected already at 2 days and remained elevated at 3 weeks, indicating an early and persistent metabolic shift. Based on diverse published literature and these initial data we suggest that increased NAD during ketolytic metabolism may be a primary mechanism behind the beneficial effects of this metabolic therapy in a variety of brain disorders and in promoting health and longevity.

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells*

Science.gov (United States)

VanLinden, Magali R.; Dölle, Christian; Pettersen, Ina K. N.; Kulikova, Veronika A.; Niere, Marc; Agrimi, Gennaro; Dyrstad, Sissel E.; Palmieri, Ferdinando; Nikiforov, Andrey A.; Tronstad, Karl Johan; Ziegler, Mathias

2015-01-01

The mitochondrial NAD pool is particularly important for the maintenance of vital cellular functions. Although at least in some fungi and plants, mitochondrial NAD is imported from the cytosol by carrier proteins, in mammals, the mechanism of how this organellar pool is generated has remained obscure. A transporter mediating NAD import into mammalian mitochondria has not been identified. In contrast, human recombinant NMNAT3 localizes to the mitochondrial matrix and is able to catalyze NAD+ biosynthesis in vitro. However, whether the endogenous NMNAT3 protein is functionally effective at generating NAD+ in mitochondria of intact human cells still remains to be demonstrated. To modulate mitochondrial NAD+ content, we have expressed plant and yeast mitochondrial NAD+ carriers in human cells and observed a profound increase in mitochondrial NAD+. None of the closest human homologs of these carriers had any detectable effect on mitochondrial NAD+ content. Surprisingly, constitutive redistribution of NAD+ from the cytosol to the mitochondria by stable expression of the Arabidopsis thaliana mitochondrial NAD+ transporter NDT2 in HEK293 cells resulted in dramatic growth retardation and a metabolic shift from oxidative phosphorylation to glycolysis, despite the elevated mitochondrial NAD+ levels. These results suggest that a mitochondrial NAD+ transporter, similar to the known one from A. thaliana, is likely absent and could even be harmful in human cells. We provide further support for the alternative possibility, namely intramitochondrial NAD+ synthesis, by demonstrating the presence of endogenous NMNAT3 in the mitochondria of human cells. PMID:26432643

Hanford recycling

Energy Technology Data Exchange (ETDEWEB)

Leonard, I.M.

1996-09-01

This paper is a study of the past and present recycling efforts on the Hanford site and options for future improvements in the recycling program. Until 1996, recycling goals were voluntarily set by the waste generators: this year, DOE has imposed goals for all its sites to accomplish by 1999. Hanford is presently meeting the voluntary site goals, but may not be able to meet all the new DOE goals without changes to the program. Most of these new DOE goals are recycling goals: * Reduce the generation of radioactive (low-level) waste from routine operations 50 percent through source reduction and recycling. * Reduce the generation of low-level mixed waste from routine operations 50 percent through source reduction and recycling. * Reduce the generation of hazardous waste from routine operations 50 percent through source reduction and recycling. * Recycle 33 percent of the sanitary waste from all operations. * Increase affirmative procurement of EPA-designated recycled items to 100 percent. The Hanford recycling program has made great strides-there has been a 98 percent increase in the amount of paper recycled since its inception in 1990. Hanford recycles paper, chemicals cardboard, tires, oil, batteries, rags, lead weights, fluorescent tubes, aerosol products, concrete, office furniture, computer software, drums, toner cartridges, and scrap metal. Many other items are recycled or reused by individual groups on a one time basis without a formal contract. Several contracts are closed-loop contracts which involve all parts of the recycle loop. Considerable savings are generated from recycling, and much more is possible with increased attention and improvements to this program. General methods for improving the recycling program to ensure that the new goals can be met are: a Contract and financial changes 0 Tracking database and methods improvements 0 Expanded recycling efforts. Specifically, the Hanford recycling program would be improved by: 0 Establishing one overall

Women and the Hanford Site

Science.gov (United States)

Gerber, Michele

2014-03-01

When we study the technical and scientific history of the Manhattan Project, women's history is sometimes left out. At Hanford, a Site whose past is rich with hard science and heavy construction, it is doubly easy to leave out women's history. After all, at the World War II Hanford Engineer Works - the earliest name for the Hanford Site - only nine percent of the employees were women. None of them were involved in construction, and only one woman was actually involved in the physics and operations of a major facility - Dr. Leona Woods Marshall. She was a physicist present at the startup of B-Reactor, the world's first full-scale nuclear reactor - now a National Historic Landmark. Because her presence was so unique, a special bathroom had to be built for her in B-Reactor. At World War II Hanford, only two women were listed among the nearly 200 members of the top supervisory staff of the prime contractor, and only one regularly attended the staff meetings of the Site commander, Colonel Franklin Matthias. Overall, women comprised less than one percent of the managerial and supervisory staff of the Hanford Engineer Works, most of them were in nursing or on the Recreation Office staff. Almost all of the professional women at Hanford were nurses, and most of the other women of the Hanford Engineer Works were secretaries, clerks, food-service workers, laboratory technicians, messengers, barracks workers, and other support service employees. The one World War II recruiting film made to attract women workers to the Site, that has survived in Site archives, is entitled ``A Day in the Life of a Typical Hanford Girl.'' These historical facts are not mentioned to criticize the past - for it is never wise to apply the standards of one era to another. The Hanford Engineer Works was a 1940s organization, and it functioned by the standards of the 1940s. Just as we cannot criticize the use of asbestos in constructing Hanford (although we may wish they hadn't used so much of it), we

Introduction to the Hanford Site

Energy Technology Data Exchange (ETDEWEB)

Cushing, C.E.

1995-06-01

This section of the 1994 Hanford Site Environmental Report discusses the Site mission and provides general information about the site. The U.S. DOE has established a new mission for Hanford including: Management of stored wastes, environmental restoration, research and development, and development of new technologies. The Hanford Reservation is located in south central Washington State just north of the confluence of the Snake and Yakima Rivers with the Columbia River. The approximately 1,450 square kilometers which comprises the Hanford Site, with restricted public access, provides a buffer for the smaller areas within the site which have historically been used for the production of nuclear materials, radioactive waste storage, and radioactive waste disposal.

Introduction to the Hanford Site

International Nuclear Information System (INIS)

Cushing, C.E.

1995-01-01

This section of the 1994 Hanford Site Environmental Report discusses the Site mission and provides general information about the site. The U.S. DOE has established a new mission for Hanford including: Management of stored wastes, environmental restoration, research and development, and development of new technologies. The Hanford Reservation is located in south central Washington State just north of the confluence of the Snake and Yakima Rivers with the Columbia River. The approximately 1,450 square kilometers which comprises the Hanford Site, with restricted public access, provides a buffer for the smaller areas within the site which have historically been used for the production of nuclear materials, radioactive waste storage, and radioactive waste disposal

The Hanford Site: An anthology of early histories

International Nuclear Information System (INIS)

Gerber, M.S.

1993-10-01

This report discusses the following topics: Memories of War: Pearl Harbor and the Genesis of the Hanford Site; safety has always been promoted at the Hanford Site; women have an important place in Hanford Site history; the boom and bust cycle: A 50-year historical overview of the economic impacts of Hanford Site Operations on the Tri-Cities, Washington; Hanford's early reactors were crucial to the sites's history; T-Plant made chemical engineering history; the UO 3 plant has a long history of service. PUREX Plant: the Hanford Site's Historic Workhorse. PUREX Plant Waste Management was a complex challenge; and early Hanford Site codes and jargon

NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+ depletion

Science.gov (United States)

Sasaki, Yo; Nakagawa, Takashi; Mao, Xianrong; DiAntonio, Aaron; Milbrandt, Jeffrey

2016-01-01

Overexpression of the NAD+ biosynthetic enzyme NMNAT1 leads to preservation of injured axons. While increased NAD+ or decreased NMN levels are thought to be critical to this process, the mechanism(s) of this axon protection remain obscure. Using steady-state and flux analysis of NAD+ metabolites in healthy and injured mouse dorsal root ganglion axons, we find that rather than altering NAD+ synthesis, NMNAT1 instead blocks the injury-induced, SARM1-dependent NAD+ consumption that is central to axon degeneration. DOI: http://dx.doi.org/10.7554/eLife.19749.001 PMID:27735788

Hanford Environmental Management Program implementation plan

International Nuclear Information System (INIS)

1988-08-01

The Hanford Environmental Management Program (HEMP) was established to facilitate compliance with the applicable environmental statues, regulations, and standards on the Hanford Site. The HEMP provides a structured approach to achieve environmental management objectives. The Hanford Environmental Management Program Plan (HEMP Plan) was prepared as a strategic level planning document to describe the program management, technical implementation, verification, and communications activities that guide the HEMP. Four basic program objectives are identified in the HEMP Plan as follows: establish ongoing monitoring to ensure that Hanford Site operations comply with environmental requirements; attain regulatory compliance through the modification of activities; mitigate any environmental consequences; and minimize the environmental impacts of future operations at the Hanford Site. 2 refs., 24 figs., 27 tabs

Adaptive changes in NAD+ metabolism in ultraviolet light-irradiated murine lymphoma cells

International Nuclear Information System (INIS)

Kleczkowska, H.E.; Szumiel, I.; Althaus, F.R.

1990-01-01

We have determined the ability of UV254nm-irradiated murine lymphoma cells to adapt their NAD+ metabolism to the increased NAD+ consumption for the poly ADP-ribosylation of chromatin proteins. Two murine lymphoma sublines with differential UV-sensitivity and poly(ADP-ribose) turnover were used as a model system. The first subline, designated LY-R is UV254nm-sensitive and tumorigenic in DBA/2 mice. The second subline, LY-S is UV254nm-resistant and nontumorigenic. Following treatment of these cells with 2 mM benzamide, an inhibitor of the NAD(+)-utilizing enzyme poly(ADP-ribose) polymerase, NAD+ levels slowly increased up to about 160% of control levels after 3 hours. When benzamide was added to these cultures 20 min after UV254nm irradiation, a dramatic transient increase of NAD+ levels was observed within 4 min in LY-R cells and more moderately in LY-S cells. At later times after UV254nm irradiation, the NAD+ levels increased in both sublines reaching up to 200% of the concentrations prior to benzamide treatment. These results demonstrate an adaptative response of NAD+ metabolism to UV254nm irradiation. In parallel, we observed a differential repartitioning of ADP-ribosyl residues between the NAD+ and poly(ADP-ribose) pools of LY-R and LY-S cells that correlates with the differential UV sensitivity of these cells

Subcellular Distribution of NAD+ between Cytosol and Mitochondria Determines the Metabolic Profile of Human Cells.

Science.gov (United States)

VanLinden, Magali R; Dölle, Christian; Pettersen, Ina K N; Kulikova, Veronika A; Niere, Marc; Agrimi, Gennaro; Dyrstad, Sissel E; Palmieri, Ferdinando; Nikiforov, Andrey A; Tronstad, Karl Johan; Ziegler, Mathias

2015-11-13

The mitochondrial NAD pool is particularly important for the maintenance of vital cellular functions. Although at least in some fungi and plants, mitochondrial NAD is imported from the cytosol by carrier proteins, in mammals, the mechanism of how this organellar pool is generated has remained obscure. A transporter mediating NAD import into mammalian mitochondria has not been identified. In contrast, human recombinant NMNAT3 localizes to the mitochondrial matrix and is able to catalyze NAD(+) biosynthesis in vitro. However, whether the endogenous NMNAT3 protein is functionally effective at generating NAD(+) in mitochondria of intact human cells still remains to be demonstrated. To modulate mitochondrial NAD(+) content, we have expressed plant and yeast mitochondrial NAD(+) carriers in human cells and observed a profound increase in mitochondrial NAD(+). None of the closest human homologs of these carriers had any detectable effect on mitochondrial NAD(+) content. Surprisingly, constitutive redistribution of NAD(+) from the cytosol to the mitochondria by stable expression of the Arabidopsis thaliana mitochondrial NAD(+) transporter NDT2 in HEK293 cells resulted in dramatic growth retardation and a metabolic shift from oxidative phosphorylation to glycolysis, despite the elevated mitochondrial NAD(+) levels. These results suggest that a mitochondrial NAD(+) transporter, similar to the known one from A. thaliana, is likely absent and could even be harmful in human cells. We provide further support for the alternative possibility, namely intramitochondrial NAD(+) synthesis, by demonstrating the presence of endogenous NMNAT3 in the mitochondria of human cells. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Hanford spent fuel inventory baseline

International Nuclear Information System (INIS)

Bergsman, K.H.

1994-01-01

This document compiles technical data on irradiated fuel stored at the Hanford Site in support of the Hanford SNF Management Environmental Impact Statement. Fuel included is from the Defense Production Reactors (N Reactor and the single-pass reactors; B, C, D, DR, F, H, KE and KW), the Hanford Fast Flux Test Facility Reactor, the Shipping port Pressurized Water Reactor, and small amounts of miscellaneous fuel from several commercial, research, and experimental reactors

NAD+ and SIRT3 control microtubule dynamics and reduce susceptibility to antimicrotubule agents

Science.gov (United States)

Harkcom, William T.; Ghosh, Ananda K.; Sung, Matthew S.; Matov, Alexandre; Brown, Kevin D.; Giannakakou, Paraskevi; Jaffrey, Samie R.

2014-01-01

Nicotinamide adenine dinucleotide (NAD+) is an endogenous enzyme cofactor and cosubstrate that has effects on diverse cellular and physiologic processes, including reactive oxygen species generation, mitochondrial function, apoptosis, and axonal degeneration. A major goal is to identify the NAD+-regulated cellular pathways that may mediate these effects. Here we show that the dynamic assembly and disassembly of microtubules is markedly altered by NAD+. Furthermore, we show that the disassembly of microtubule polymers elicited by microtubule depolymerizing agents is blocked by increasing intracellular NAD+ levels. We find that these effects of NAD+ are mediated by the activation of the mitochondrial sirtuin sirtuin-3 (SIRT3). Overexpression of SIRT3 prevents microtubule disassembly and apoptosis elicited by antimicrotubule agents and knockdown of SIRT3 prevents the protective effects of NAD+ on microtubule polymers. Taken together, these data demonstrate that NAD+ and SIRT3 regulate microtubule polymerization and the efficacy of antimicrotubule agents. PMID:24889606

Statistical Methods and Tools for Hanford Staged Feed Tank Sampling

Energy Technology Data Exchange (ETDEWEB)

Fountain, Matthew S. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Brigantic, Robert T. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Peterson, Reid A. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

2013-10-01

This report summarizes work conducted by Pacific Northwest National Laboratory to technically evaluate the current approach to staged feed sampling of high-level waste (HLW) sludge to meet waste acceptance criteria (WAC) for transfer from tank farms to the Hanford Waste Treatment and Immobilization Plant (WTP). The current sampling and analysis approach is detailed in the document titled Initial Data Quality Objectives for WTP Feed Acceptance Criteria, 24590-WTP-RPT-MGT-11-014, Revision 0 (Arakali et al. 2011). The goal of this current work is to evaluate and provide recommendations to support a defensible, technical and statistical basis for the staged feed sampling approach that meets WAC data quality objectives (DQOs).

Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease

Directory of Open Access Journals (Sweden)

Susann Lehmann

2017-02-01

Full Text Available Familial forms of Parkinson's disease (PD caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD+ is essential for both generating energy in mitochondria and nuclear DNA repair through NAD+-consuming poly(ADP-ribose polymerases (PARPs. We found alterations in NAD+ salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD+ precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration. Additionally, a mutation of Parp improved mitochondrial function and was neuroprotective in the pink1 mutants. We conclude that enhancing the availability of NAD+ by either the use of a diet supplemented with NAD+ precursors or the inhibition of NAD+-dependent enzymes, such as PARPs, which compete with mitochondria for NAD+, is a viable approach to preventing neurotoxicity associated with mitochondrial defects.

Engineering Task Plan for the Ultrasonic Inspection of Hanford Double-Shell Tanks - FY 2001

International Nuclear Information System (INIS)

JENSEN, C.E.

2000-01-01

This document facilitates the ultrasonic examination of Hanford double-shell tanks. Included are a plan for engineering activities, plan for performance demonstration testing, and a plan for field activities. Also included are a Statement of Work for contractor performance and a protocol to be followed should tank flaws that exceed the acceptance criteria are found

Simultaneous measurement of NAD metabolome in aged mice tissue using liquid chromatography tandem-mass spectrometry.

Science.gov (United States)

Yaku, Keisuke; Okabe, Keisuke; Nakagawa, Takashi

2018-06-01

Nicotinamide adenine dinucleotide (NAD) is a major co-factor that mediates multiple biological processes including redox reaction and gene expression. Recently, NAD metabolism has received considerable attention because administration of NAD precursors exhibited beneficial effects against aging-related metabolic disorders in animals. Although numerous studies have reported that NAD levels decline with aging in multiple animal tissues, the pathway and kinetics of NAD metabolism in aged organs are not completely understood. To determine the NAD metabolism upon aging, we developed targeted metabolomics based on an LC/MS/MS system. Our method is simple and applicable to crude biological samples, including culture cells and animal tissues. Unlike a conventional enzymatic cycling assay, our approach can determine NAD and NADH (reduced form of NAD) by performing a single sample preparation. Further, we validated our method using biological samples and investigated the alteration of the NAD metabolome during aging. Consistent with previous reports, the NAD levels in the liver and skeletal muscle decreased with aging. Further, we detected a significant increase in nicotinamide mononucleotide and nicotinamide riboside in the kidney upon aging. The LC/MS/MS-based NAD metabolomics that we have developed is extensively applicable to biomedical studies, and the results will present innovative ideas for the aging studies, especially for that of NAD metabolism. Copyright © 2018 John Wiley & Sons, Ltd.

Hanford Site Tank Waste Remediation System

International Nuclear Information System (INIS)

1993-05-01

The US Department of Energy's (DOE) Hanford Site in southeastern Washington State has the most diverse and largest amount of highly radioactive waste of any site in the US. High-level radioactive waste has been stored in large underground tanks since 1944. A Tank Waste Remediation System Program has been established within the DOE to safely manage and immobilize these wastes in anticipation of permanent disposal in a geologic repository. The Hanford Site Tank Waste Remediation System Waste Management 1993 Symposium Papers and Viewgraphs covered the following topics: Hanford Site Tank Waste Remediation System Overview; Tank Waste Retrieval Issues and Options for their Resolution; Tank Waste Pretreatment - Issues, Alternatives and Strategies for Resolution; Low-Level Waste Disposal - Grout Issue and Alternative Waste Form Technology; A Strategy for Resolving High-Priority Hanford Site Radioactive Waste Storage Tank Safety Issues; Tank Waste Chemistry - A New Understanding of Waste Aging; Recent Results from Characterization of Ferrocyanide Wastes at the Hanford Site; Resolving the Safety Issue for Radioactive Waste Tanks with High Organic Content; Technology to Support Hanford Site Tank Waste Remediation System Objectives

Hanford Site Development Plan

International Nuclear Information System (INIS)

Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J.; Yancey, E.F.

1990-01-01

The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs

Hanford Site Development Plan

Energy Technology Data Exchange (ETDEWEB)

Rinne, C.A.; Curry, R.H.; Hagan, J.W.; Seiler, S.W.; Sommer, D.J. (Westinghouse Hanford Co., Richland, WA (USA)); Yancey, E.F. (Pacific Northwest Lab., Richland, WA (USA))

1990-01-01

The Hanford Site Development Plan (Site Development Plan) is intended to guide the short- and long-range development and use of the Hanford Site. All acquisition, development, and permanent facility use at the Hanford Site will conform to the approved plan. The Site Development Plan also serves as the base document for all subsequent studies that involve use of facilities at the Site. This revision is an update of a previous plan. The executive summary presents the highlights of the five major topics covered in the Site Development Plan: general site information, existing conditions, planning analysis, Master Plan, and Five-Year Plan. 56 refs., 67 figs., 31 tabs.

Synthesizing and salvaging NAD: lessons learned from Chlamydomonas reinhardtii.

Directory of Open Access Journals (Sweden)

Huawen Lin

2010-09-01

Full Text Available The essential coenzyme nicotinamide adenine dinucleotide (NAD+ plays important roles in metabolic reactions and cell regulation in all organisms. Bacteria, fungi, plants, and animals use different pathways to synthesize NAD+. Our molecular and genetic data demonstrate that in the unicellular green alga Chlamydomonas NAD+ is synthesized from aspartate (de novo synthesis, as in plants, or nicotinamide, as in mammals (salvage synthesis. The de novo pathway requires five different enzymes: L-aspartate oxidase (ASO, quinolinate synthetase (QS, quinolate phosphoribosyltransferase (QPT, nicotinate/nicotinamide mononucleotide adenylyltransferase (NMNAT, and NAD+ synthetase (NS. Sequence similarity searches, gene isolation and sequencing of mutant loci indicate that mutations in each enzyme result in a nicotinamide-requiring mutant phenotype in the previously isolated nic mutants. We rescued the mutant phenotype by the introduction of BAC DNA (nic2-1 and nic13-1 or plasmids with cloned genes (nic1-1 and nic15-1 into the mutants. NMNAT, which is also in the de novo pathway, and nicotinamide phosphoribosyltransferase (NAMPT constitute the nicotinamide-dependent salvage pathway. A mutation in NAMPT (npt1-1 has no obvious growth defect and is not nicotinamide-dependent. However, double mutant strains with the npt1-1 mutation and any of the nic mutations are inviable. When the de novo pathway is inactive, the salvage pathway is essential to Chlamydomonas for the synthesis of NAD+. A homolog of the human SIRT6-like gene, SRT2, is upregulated in the NS mutant, which shows a longer vegetative life span than wild-type cells. Our results suggest that Chlamydomonas is an excellent model system to study NAD+ metabolism and cell longevity.

Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis.

Science.gov (United States)

Wang, Guodong; Pichersky, Eran

2007-03-01

Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which is derived from NAD, have important roles as a redox carriers in metabolism. A combination of de novo and salvage pathways contribute to the biosynthesis of NAD in all organisms. The pathways and enzymes of the NAD salvage pathway in yeast and animals, which diverge at nicotinamide, have been extensively studied. Yeast cells convert nicotinamide to nicotinic acid, while mammals lack the enzyme nicotinamidase and instead convert nicotinamide to nicotinamide mononucleotide. Here we show that Arabidopsis thaliana gene At2g22570 encodes a nicotinamidase, which is expressed in all tissues, with the highest levels observed in roots and stems. The 244-residue protein, designated AtNIC1, converts nicotinamide to nicotinic acid and has a Km value of 118 +/- 17 microM and a Kcat value of 0.93 +/- 0.13 sec(-1). Plants homozygous for a null AtNIC1 allele, nic1-1, have lower levels of NAD and NADP under normal growth conditions, indicating that AtNIC1 participates in a yeast-type NAD salvage pathway. Mutant plants also exhibit hypersensitivity to treatments of abscisic acid and NaCl, which is correlated with their inability to increase the cellular levels of NAD(H) under these growth conditions, as occurs in wild-type plants. We also show that the growth of the roots of wild-type but not nic1-1 mutant plants is inhibited and distorted by nicotinamide.

Hanford defense waste studies

International Nuclear Information System (INIS)

Napier, B.A.; Zimmerman, M.G.; Soldat, J.K.

1981-01-01

PNL is assisting Rockwell Hanford Operations to prepare a programmatic environmental impact statement for the management of Hanford defense nuclear waste. The Ecological Sciences Department is leading the task of calculation of public radiation doses from a large matrix of potential routine and accidental releases of radionuclides to the environment

NHC's contribution to cleanup of the Hanford Site

International Nuclear Information System (INIS)

Chauve, H.D.

1998-01-01

The one billion dollars per year Project Hanford Management Contract (PHMC), managed by Fluor Daniel Hanford, calls for cleanup of the Hanford Site for the Department of Energy. Project Hanford comprises four major subprojects, each managed by a different major contractor. Numatec Hanford Corporation (NHC) is a fifth major subcontractor which provides energy and technology to each of the Hanford projects. NHC draws on the experience and capabilities of its parent companies, COGEMA and SGN, and relies on local support from its sister Company in Richland, COGEMA Engineering Corporation, to bring the best commercial practices and new technology to the Project

Metabolic control by sirtuins and other enzymes that sense NAD(+), NADH, or their ratio

DEFF Research Database (Denmark)

Anderson, Kristin A; Madsen, Andreas S; Olsen, Christian A

2017-01-01

NAD(+) is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD(+), NADH, and the NAD(+)/NADH ratio have long been known to control the activity of several...... oxidoreductase enzymes. More recently, enzymes outside those participating directly in redox control have been identified that sense these dinucleotides, including the sirtuin family of NAD(+)-dependent protein deacylases. In this review, we highlight examples of non-redox enzymes that are controlled by NAD......(+), NADH, or NAD(+)/NADH. In particular, we focus on the sirtuin family and assess the current evidence that the sirtuin enzymes sense these dinucleotides and discuss the biological conditions under which this might occur; we conclude that sirtuins sense NAD(+), but neither NADH nor the ratio. Finally, we...

Elongator Plays a Positive Role in Exogenous NAD-Induced Defense Responses in Arabidopsis.

Science.gov (United States)

An, Chuanfu; Ding, Yezhang; Zhang, Xudong; Wang, Chenggang; Mou, Zhonglin

2016-05-01

Extracellular NAD is emerging as an important signal molecule in animal cells, but its role in plants has not been well-established. Although it has been shown that exogenous NAD(+) activates defense responses in Arabidopsis, components in the exogenous NAD(+)-activated defense pathway remain to be fully discovered. In a genetic screen for mutants insensitive to exogenous NAD(+) (ien), we isolated a mutant named ien2. Map-based cloning revealed that IEN2 encodes ELONGATA3 (ELO3)/AtELP3, a subunit of the Arabidopsis Elongator complex, which functions in multiple biological processes, including histone modification, DNA (de)methylation, and transfer RNA modification. Mutations in the ELO3/AtELP3 gene compromise exogenous NAD(+)-induced expression of pathogenesis-related (PR) genes and resistance to the bacterial pathogen Pseudomonas syringae pv. maculicola ES4326, and transgenic expression of the coding region of ELO3/AtELP3 in elo3/Atelp3 restores NAD(+) responsiveness to the mutant plants, demonstrating that ELO3/AtELP3 is required for exogenous NAD(+)-induced defense responses. Furthermore, mutations in genes encoding the other five Arabidopsis Elongator subunits (ELO2/AtELP1, AtELP2, ELO1/AtELP4, AtELP5, and AtELP6) also compromise exogenous NAD(+)-induced PR gene expression and resistance to P. syringae pv. maculicola ES4326. These results indicate that the Elongator complex functions as a whole in exogenous NAD(+)-activated defense signaling in Arabidopsis.

Tank Waste Transport Stability: Summaries of Hanford Slurry and Salt-Solution Studies in FY 2000

Energy Technology Data Exchange (ETDEWEB)

Welch, T.D.

2002-07-08

This report is a collection of summary articles on FY 2000 studies of slurry transport and salt-well pumping related to Hanford tank waste transfers. These studies are concerned with the stability (steady, uninterrupted flow) of tank waste transfers, a subset of the Department of Energy (DOE) Tanks Focus Area Tank (TFA) Waste Chemistry effort. This work is a collaborative effort of AEA Technology plc, the Diagnostic Instrumentation and Analysis Laboratory at Mississippi State University (DIAL-MSU), the Hemispheric Center for Environmental Technology at Florida International University (HCET-FIU), Numatec Hanford Corporation (NHC), and the Oak Ridge National Laboratory (ORNL). The purpose of this report is to provide, in a single document, an overview of these studies to help the reader identify contacts and resources for obtaining more detailed information and to help promote useful interchanges between researchers and users. Despite over 50 years of experience in transporting radioactive tank wastes to and from equipment and tanks at the Department of Energy's Hanford, Savannah River, and Oak Ridge sites, waste slurry transfer pipelines and process piping become plugged on occasion. At Hanford, several tank farm pipelines are no longer in service because of plugs. At Savannah River, solid deposits in the outlet line of the 2H evaporator have resulted in an unplanned extended downtime. Although waste transfer criteria and guidelines intended to prevent pipeline plugging are in place, they are not always adequate. To avoid pipeline plugging in the future, other factors that are not currently embodied in the transfer criteria may need to be considered. The work summarized here is being conducted to develop a better understanding of the chemical and waste flow dynamics during waste transfer. The goal is to eliminate pipeline plugs by improving analysis and engineering tools in the field that incorporate this understanding.

Hanford Site baseline risk assessment methodology

International Nuclear Information System (INIS)

1993-03-01

This methodology has been developed to prepare human health and environmental evaluations of risk as part of the Comprehensive Environmental Response, Compensation, and Liability Act remedial investigations (RIs) and the Resource Conservation and Recovery Act facility investigations (FIs) performed at the Hanford Site pursuant to the Hanford Federal Facility Agreement and Consent Order referred to as the Tri-Party Agreement. Development of the methodology has been undertaken so that Hanford Site risk assessments are consistent with current regulations and guidance, while providing direction on flexible, ambiguous, or undefined aspects of the guidance. The methodology identifies Site-specific risk assessment considerations and integrates them with approaches for evaluating human and environmental risk that can be factored into the risk assessment program supporting the Hanford Site cleanup mission. Consequently, the methodology will enhance the preparation and review of individual risk assessments at the Hanford Site

Hanford Site 1998 Environmental Report

Energy Technology Data Exchange (ETDEWEB)

RL Dirkes; RW Hanf; TM Poston

1999-09-21

This Hanford Site environmental report is prepared annually to summarize environmental data and information, to describe environmental management performance, to demonstrate the status of compliance with environmental regulations, and to highlight major environmental programs and efforts. The report is written to meet requirements and guidelines of the U.S. Department of Energy (DOE) and to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to: describe the Hanford Site and its mission; summarize the status of compliance with environmental regulations; describe the environmental programs at the Hanford Site; discuss the estimated radionuclide exposure to the public from 1998 Hanford Site activities; present the effluent monitoring, environmental surveillance, and groundwater protection and monitoring information; and discuss the activities to ensure quality.

Metabolic control by sirtuins and other enzymes that sense NAD+, NADH, or their ratio.

Science.gov (United States)

Anderson, Kristin A; Madsen, Andreas S; Olsen, Christian A; Hirschey, Matthew D

2017-12-01

NAD + is a dinucleotide cofactor with the potential to accept electrons in a variety of cellular reduction-oxidation (redox) reactions. In its reduced form, NADH is a ubiquitous cellular electron donor. NAD + , NADH, and the NAD + /NADH ratio have long been known to control the activity of several oxidoreductase enzymes. More recently, enzymes outside those participating directly in redox control have been identified that sense these dinucleotides, including the sirtuin family of NAD + -dependent protein deacylases. In this review, we highlight examples of non-redox enzymes that are controlled by NAD + , NADH, or NAD + /NADH. In particular, we focus on the sirtuin family and assess the current evidence that the sirtuin enzymes sense these dinucleotides and discuss the biological conditions under which this might occur; we conclude that sirtuins sense NAD + , but neither NADH nor the ratio. Finally, we identify future studies that might be informative to further interrogate physiological and pathophysiological changes in NAD + and NADH, as well as enzymes like sirtuins that sense and respond to redox changes in the cell. Copyright © 2017 Elsevier B.V. All rights reserved.

Biosynthesis of NAD from nicotinic acid and nicotinamide by resting cells of Arthrobacter globiformis

International Nuclear Information System (INIS)

Kuwahara, Masaaki

1978-01-01

Isotopically labeled nicotinic acid and nicotinamide were incorporated into the metabolites of nicotinic acid-dependent pathway (Preiss-Handler pathway) of the NAD biosynthesis by resting cells of Arthrobacter globiformis. Azaserine and adenosine markedly stimulated the accumulation of NAD in the cells. Radioactive nicotinic acid and nicotinamide were also incorporated into an unknown compound when the cells were incubated in the presence of azaserine. Cell-free extract of the organism showed the NAD synthetase activity, which required ammonium ion and ATP for the amidation of deamido-NAD. Adenosine inhibited the enzyme activity. The organism possessed nicotinamidase, suggesting deamidation is the first step in the biosynthesis of NAD from nicotinamide. The activity was inhibited by NAD, NADP and NMN. (auth.)

Hanford Site ground-water surveillance for 1989

International Nuclear Information System (INIS)

Evans, J.C.; Bryce, R.W.; Bates, D.J.; Kemner, M.L.

1990-06-01

This annual report of ground-water surveillance activities provides discussions and listings of results for ground-water monitoring at the Hanford Site during 1989. The Pacific Northwest Laboratory (PNL) assesses the impacts of Hanford operations on the environment for the US Department of Energy (DOE). The impact Hanford operations has on ground water is evaluated through the Hanford Site Ground-Water Surveillance program. Five hundred and sixty-seven wells were sampled during 1989 for Hanford ground-water monitoring activities. This report contains a listing of analytical results for calendar year (CY) 1989 for species of importance as potential contaminants. 30 refs., 29 figs,. 4 tabs

Mitochondrial type II NAD(PH dehydrogenases in fungal cell death

Directory of Open Access Journals (Sweden)

A. Pedro Gonçalves

2015-03-01

Full Text Available During aerobic respiration, cells produce energy through oxidative phosphorylation, which includes a specialized group of multi-subunit complexes in the inner mitochondrial membrane known as the electron transport chain. However, this canonical pathway is branched into single polypeptide alternative routes in some fungi, plants, protists and bacteria. They confer metabolic plasticity, allowing cells to adapt to different environmental conditions and stresses. Type II NAD(PH dehydrogenases (also called alternative NAD(PH dehydrogenases are non-proton pumping enzymes that bypass complex I. Recent evidence points to the involvement of fungal alternative NAD(PH dehydrogenases in the process of programmed cell death, in addition to their action as overflow systems upon oxidative stress. Consistent with this, alternative NAD(PH dehydrogenases are phylogenetically related to cell death - promoting proteins of the apoptosis-inducing factor (AIF-family.

Criteria: waste tank isolation and stabilization

Energy Technology Data Exchange (ETDEWEB)

Metz, W.P.; Ogren, W.E.

1976-09-01

The crystallized Hanford high-level wastes stored in single-shell underground tanks consist of sludges and salt cakes covered with supernatural liquor. Purpose of stabilization and isolation is to reduce the releases and losses as a result of a loss of tank integrity. The tanks will be modified so that no inadvertent liquid additions can be made. Criteria for the isolation and stabilization are given and discussed briefly. (DLC)

Criteria: waste tank isolation and stabilization

International Nuclear Information System (INIS)

Metz, W.P.; Ogren, W.E.

1976-09-01

The crystallized Hanford high-level wastes stored in single-shell underground tanks consist of sludges and salt cakes covered with supernatural liquor. Purpose of stabilization and isolation is to reduce the releases and losses as a result of a loss of tank integrity. The tanks will be modified so that no inadvertent liquid additions can be made. Criteria for the isolation and stabilization are given and discussed briefly

Increasing NAD Synthesis in Muscle via Nicotinamide Phosphoribosyltransferase Is Not Sufficient to Promote Oxidative Metabolism*

Science.gov (United States)

Frederick, David W.; Davis, James G.; Dávila, Antonio; Agarwal, Beamon; Michan, Shaday; Puchowicz, Michelle A.; Nakamaru-Ogiso, Eiko; Baur, Joseph A.

2015-01-01

The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. PMID:25411251

Depletion of NAD pool contributes to impairment of endothelial progenitor cell mobilization in diabetes.

Science.gov (United States)

Wang, Pei; Yang, Xi; Zhang, Zheng; Song, Jie; Guan, Yun-Feng; Zou, Da-Jin; Miao, Chao-Yu

2016-06-01

The impaired mobilization of endothelial progenitor cells (EPCs) from bone marrow (BM) critically contributes to the diabetes-associated vascular complications. Here, we investigated the relationship between the nicotinamide phosphoribosyltransferase (NAMPT)-controlled nicotinamide adenine dinucleotide (NAD) metabolism and the impaired mobilization of BM-derived EPCs in diabetic condition. The NAMPT-NAD pool in BM and BM-derived EPCs in wild-type (WT) and diabetic db/db mice was determined. Nicotinamide, a natural substrate for NAD biosynthesis, was administrated for 2weeks in db/db mice to examine the influence of enhancing NAD pool on BM and blood EPCs number. The modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein in BM were measured using immunoblotting. The EPCs intracellular NAMPT level and NAD concentration, as well as the blood EPCs number, were compared between 9 healthy people and 16 patients with type 2 diabetes mellitus (T2DM). The T2DM patients were treated with nicotinamide for two weeks and then the blood EPCs number was determined. Moreover, the association between blood EPCs numbers and EPCs intracellular NAD(+)/NAMPT protein levels in 21 healthy individuals was determined. We found that NAD concentration and NAMPT expression in BM and BM-derived EPCs of db/db mice were significantly lower than those in WT mice BM. Enhancing NAD pool not only increased the EPCs intracellular NAD concentration and blood EPCs number, but also improved post-ischemic wound healing and blood reperfusion in db/db mice with hind-limb ischemia model. Enhancing NAD pool rescued the impaired modulations of stromal cell-derived factor-1α (SDF-1α) and endothelial nitric oxide synthase (eNOS) protein levels in db/db mice BM upon hind-limb ischemia. In addition, enhancing NAD pool significantly inhibited PARP and caspase-3 activates in db/db mice BM. The intracellular NAMPT-NAD pool was positively associated with blood

Savannah River Site Bagless Transfer Technology Applied at Hanford

International Nuclear Information System (INIS)

Wong, J.W.

2001-01-01

A ''bagless transfer'' process was developed at the Savannah River Site (SRS) to remove radioactive materials from glovebox enclosures for long-term storage in conformance with DOE Standard 3013. This process, unlike the more conventional ''bag-out'' process, produces an all-metal, helium-filled, welded storage container that does not contain materials subject to radiolytic decomposition. A Bagless Transfer System (BTS), utilizing this bagless transfer process, has been in service at SRS since August 1997. It is a semi-automated system that has proven to be very reliable during its three years of operation.The Plutonium Finishing Plant (PFP) at Hanford has a similar need for long-term storage of radioactive materials. The successful operation of the Savannah River Site BTS led to the selection of the same technology to fulfill the packaging need at Hanford. However, there are a number of differences between the existing SRS BTS and the system currently in operation at Hanford. These differences will be discussed in this paper. Additionally, a system is necessary to produce another all-metal, welded container into which the container produced by the BTS can be placed. This container must be in conformance with the criteria specified in DOE-STD-3013 for an outer container. SRS Engineers are developing a system (outer container welder), based on the tungsten inert gas (TIG) welding equipment used in the BTS, to produce this outer container

NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation.

Science.gov (United States)

Ryu, Dongryeol; Zhang, Hongbo; Ropelle, Eduardo R; Sorrentino, Vincenzo; Mázala, Davi A G; Mouchiroud, Laurent; Marshall, Philip L; Campbell, Matthew D; Ali, Amir Safi; Knowels, Gary M; Bellemin, Stéphanie; Iyer, Shama R; Wang, Xu; Gariani, Karim; Sauve, Anthony A; Cantó, Carles; Conley, Kevin E; Walter, Ludivine; Lovering, Richard M; Chin, Eva R; Jasmin, Bernard J; Marcinek, David J; Menzies, Keir J; Auwerx, Johan

2016-10-19

Neuromuscular diseases are often caused by inherited mutations that lead to progressive skeletal muscle weakness and degeneration. In diverse populations of normal healthy mice, we observed correlations between the abundance of mRNA transcripts related to mitochondrial biogenesis, the dystrophin-sarcoglycan complex, and nicotinamide adenine dinucleotide (NAD + ) synthesis, consistent with a potential role for the essential cofactor NAD + in protecting muscle from metabolic and structural degeneration. Furthermore, the skeletal muscle transcriptomes of patients with Duchene's muscular dystrophy (DMD) and other muscle diseases were enriched for various poly[adenosine 5'-diphosphate (ADP)-ribose] polymerases (PARPs) and for nicotinamide N-methyltransferase (NNMT), enzymes that are major consumers of NAD + and are involved in pleiotropic events, including inflammation. In the mdx mouse model of DMD, we observed significant reductions in muscle NAD + levels, concurrent increases in PARP activity, and reduced expression of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme for NAD + biosynthesis. Replenishing NAD + stores with dietary nicotinamide riboside supplementation improved muscle function and heart pathology in mdx and mdx/Utr -/- mice and reversed pathology in Caenorhabditis elegans models of DMD. The effects of NAD + repletion in mdx mice relied on the improvement in mitochondrial function and structural protein expression (α-dystrobrevin and δ-sarcoglycan) and on the reductions in general poly(ADP)-ribosylation, inflammation, and fibrosis. In combination, these studies suggest that the replenishment of NAD + may benefit patients with muscular dystrophies or other neuromuscular degenerative conditions characterized by the PARP/NNMT gene expression signatures. Copyright © 2016, American Association for the Advancement of Science.

Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy.

Science.gov (United States)

Yamaguchi, Shintaro; Yoshino, Jun

2017-05-01

Nicotinamide adenine dinucleotide (NAD + ) biosynthetic pathway, mediated by nicotinamide phosphoribosyltransferase (NAMPT), a key NAD + biosynthetic enzyme, plays a pivotal role in controlling many biological processes, such as metabolism, circadian rhythm, inflammation, and aging. Over the past decade, NAMPT-mediated NAD + biosynthesis, together with its key downstream mediator, namely the NAD + -dependent protein deacetylase SIRT1, has been demonstrated to regulate glucose and lipid metabolism in a tissue-dependent manner. These discoveries have provided novel mechanistic and therapeutic insights into obesity and its metabolic complications, such as insulin resistance, an important risk factor for developing type 2 diabetes and cardiovascular disease. This review will focus on the importance of adipose tissue NAMPT-mediated NAD + biosynthesis and SIRT1 in the pathophysiology of obesity and insulin resistance. We will also critically explore translational and clinical aspects of adipose tissue NAD + biology. © 2017 WILEY Periodicals, Inc.

NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy

Science.gov (United States)

Goody, Michelle F.; Kelly, Meghan W.; Reynolds, Christine J.; Khalil, Andre; Crawford, Bryan D.; Henry, Clarissa A.

2012-01-01

Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex– or integrin alpha7–deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin

NAD+ biosynthesis ameliorates a zebrafish model of muscular dystrophy.

Directory of Open Access Journals (Sweden)

Michelle F Goody

Full Text Available Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction

Sources and implications of NADH/NAD+ redox imbalance in diabetes and its complications

Directory of Open Access Journals (Sweden)

Wu J

2016-05-01

Full Text Available Jinzi Wu,1Zhen Jin,1Hong Zheng,1,2Liang-Jun Yan1 1Department of Pharmaceutical Sciences, UNT System College of Pharmacy, University of North Texas Health Science Center, Fort Worth, TX, USA; 2Department of Basic Theory of Traditional Chinese Medicine, College of Basic Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People’s Republic of China Abstract: NAD+ is a fundamental molecule in metabolism and redox signaling. In diabetes and its complications, the balance between NADH and NAD+ can be severely perturbed. On one hand, NADH is overproduced due to influx of hyperglycemia to the glycolytic and Krebs cycle pathways and activation of the polyol pathway. On the other hand, NAD+ can be diminished or depleted by overactivation of poly ADP ribose polymerase that uses NAD+ as its substrate. Moreover, sirtuins, another class of enzymes that also use NAD+ as their substrate for catalyzing protein deacetylation reactions, can also affect cellular content of NAD+. Impairment of NAD+ regeneration enzymes such as lactate dehydrogenase in erythrocytes and complex I in mitochondria can also contribute to NADH accumulation and NAD+ deficiency. The consequence of NADH/NAD+ redox imbalance is initially reductive stress that eventually leads to oxidative stress and oxidative damage to macromolecules, including DNA, lipids, and proteins. Accordingly, redox imbalance-triggered oxidative damage has been thought to be a major factor contributing to the development of diabetes and its complications. Future studies on restoring NADH/NAD+ redox balance could provide further insights into design of novel antidiabetic strategies. Keywords: mitochondria, complex I, reactive oxygen species, polyol pathway, poly ADP ribosylation, sirtuins, oxidative stress, oxidative damage

HANFORD SCIENCE & TECHNOLOGY NEEDS STATEMENTS 2002

Energy Technology Data Exchange (ETDEWEB)

WIBLE, R.A.

2002-04-01

This document: (a) provides a comprehensive listing of the Hanford sites science and technology needs for fiscal year (FY) 2002; and (b) identifies partnering and commercialization opportunities within industry, other federal and state agencies, and the academic community. These needs were prepared by the Hanford projects (within the Project Hanford Management Contract, the Environmental Restoration Contract and the River Protection Project) and subsequently reviewed and endorsed by the Hanford Site Technology Coordination Group (STCG). The STCG reviews included participation of DOE-RL and DOE-ORP Management, site stakeholders, state and federal regulators, and Tribal Nations. These needs are reviewed and updated on an annual basis and given a broad distribution.

Pollution prevention opportunity assessments at Hanford

Energy Technology Data Exchange (ETDEWEB)

Betsch, M.D., Westinghouse Hanford

1996-06-26

The Pollution Prevention Opportunity Assessment (PPOA) is a pro- active way to look at a waste generating activity and identify opportunities to minimize wastes through a cost benefit analysis. Hanford`s PPOA process is based upon the graded approach developed by the Kansas City Plant. Hanford further streamlined the process while building in more flexibility for the individual users. One of the most challenging aspects for implementing the PPOA process at Hanford is one overall mission which is environmental restoration, Now that the facilities are no longer in production, each has a different non- routine activity making it difficult to quantify the inputs and outputs of the activity under consideration.

HANFORD SITE RIVER PROTECTION PROJECT (RPP) TANK FARM CLOSURE

International Nuclear Information System (INIS)

JARAYSI, M.N.; SMITH, Z.; QUINTERO, R.; BURANDT, M.B.; HEWITT, W.

2006-01-01

retrieval of the waste is under way and is being conducted to achieve the completion criteria established in the Hanford Federal Facility Agreement and Consent Order

Hanford Sitewide Groundwater Remediation Strategy

International Nuclear Information System (INIS)

Knepp, A.J.; Isaacs, J.D.

1997-09-01

This document fulfills the requirements of the Hanford Federal Facility Agreement and Consent Order, Milestone M-13-81, to develop a concise statement of strategy that describe show the Hanford Site groundwater remediation will be accomplished. The strategy addresses objectives and goals, prioritization of activities, and technical approaches for groundwater cleanup. The strategy establishes that the overall goal of groundwater remediation on the Hanford Site is to restore groundwater to its beneficial uses in terms of protecting human health and the environment, and its use as a natural resource. The Hanford Future Site Uses Working Group established two categories for groundwater commensurate with various proposed landuses: (1) restricted use or access to groundwater in the Central Plateau and in a buffer zone surrounding it and (2) unrestricted use or access to groundwater for all other areas. In recognition of the Hanford Future Site Uses Working Group and public values, the strategy establishes that the sitewide approach to groundwater cleanup is to remediate the major plumes found in the reactor areas that enter the Columbia River and to contain the spread and reduce the mass of the major plumes found in the Central Plateau

Dual emission fluorescent silver nanoclusters for sensitive detection of the biological coenzyme NAD+/NADH.

Science.gov (United States)

Yuan, Yufeng; Huang, Kehan; Chang, Mengfang; Qin, Cuifang; Zhang, Sanjun; Pan, Haifeng; Chen, Yan; Xu, Jianhua

2016-02-01

Fluorescent silver nanoclusters (Ag NCs) displaying dual-excitation and dual-emission properties have been developed for the specific detection of NAD(+) (nicotinamide adenine dinucleotide, oxidized form). With the increase of NAD(+) concentrations, the longer wavelength emission (with the peak at 550 nm) was gradually quenched due to the strong interactions between the NAD(+) and Ag NCs, whereas the shorter wavelength emission (peaking at 395 nm) was linearly enhanced. More important, the dual-emission intensity ratio (I395/I550), fitting by a single-exponential decay function, can efficiently detect various NAD(+) levels from 100 to 4000 μM, as well as label NAD(+)/NADH (reduced form of NAD) ratios in the range of 1-50. Copyright © 2015 Elsevier Inc. All rights reserved.

An Integrated Biological Control System At Hanford

International Nuclear Information System (INIS)

Johnson, A.R.; Caudill, J.G.; Giddings, R.F.; Rodriguez, J.M.; Roos, R.C.; Wilde, J.W.

2010-01-01

In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimate spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

AN INTEGRATED BIOLOGICAL CONTROL SYSTEM AT HANFORD

Energy Technology Data Exchange (ETDEWEB)

JOHNSON AR; CAUDILL JG; GIDDINGS RF; RODRIGUEZ JM; ROOS RC; WILDE JW

2010-02-11

In 1999 an integrated biological control system was instituted at the U.S. Department of Energy's Hanford Site. Successes and changes to the program needed to be communicated to a large and diverse mix of organizations and individuals. Efforts at communication are directed toward the following: Hanford Contractors (Liquid or Tank Waste, Solid Waste, Environmental Restoration, Science and Technology, Site Infrastructure), General Hanford Employees, and Hanford Advisory Board (Native American Tribes, Environmental Groups, Local Citizens, Washington State and Oregon State regulatory agencies). Communication was done through direct interface meetings, individual communication, where appropriate, and broadly sharing program reports. The objectives of the communication efforts was to have the program well coordinated with Hanford contractors, and to have the program understood well enough that all stakeholders would have confidence in the work performed by the program to reduce or elimated spread of radioactive contamination by biotic vectors. Communication of successes and changes to an integrated biological control system instituted in 1999 at the Department of Energy's Hanford Site have required regular interfaces with not only a diverse group of Hanford contractors (i.e., those responsible for liquid or tank waste, solid wastes, environmental restoration, science and technology, and site infrastructure), and general Hanford employees, but also with a consortium of designated stake holders organized as the Hanford Advisory Board (i.e., Native American tribes, various environmental groups, local citizens, Washington state and Oregon regulatory agencies, etc.). Direct interface meetings, individual communication where appropriate, and transparency of the biological control program were the methods and outcome of this effort.

A conserved NAD+ binding pocket that regulates protein-protein interactions during aging.

Science.gov (United States)

Li, Jun; Bonkowski, Michael S; Moniot, Sébastien; Zhang, Dapeng; Hubbard, Basil P; Ling, Alvin J Y; Rajman, Luis A; Qin, Bo; Lou, Zhenkun; Gorbunova, Vera; Aravind, L; Steegborn, Clemens; Sinclair, David A

2017-03-24

DNA repair is essential for life, yet its efficiency declines with age for reasons that are unclear. Numerous proteins possess Nudix homology domains (NHDs) that have no known function. We show that NHDs are NAD + (oxidized form of nicotinamide adenine dinucleotide) binding domains that regulate protein-protein interactions. The binding of NAD + to the NHD domain of DBC1 (deleted in breast cancer 1) prevents it from inhibiting PARP1 [poly(adenosine diphosphate-ribose) polymerase], a critical DNA repair protein. As mice age and NAD + concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD + Thus, NAD + directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging. Copyright © 2017, American Association for the Advancement of Science.

Hanford Waste Management Plan, 1987

International Nuclear Information System (INIS)

1987-01-01

The purpose of the Hanford Waste Management Plan (HWMP) is to provide an integrated plan for the safe storage, interim management, and disposal of existing waste sites and current and future waste streams at the Hanford Site. The emphasis of this plan is, however, on the disposal of Hanford Site waste. The plans presented in the HWMP are consistent with the preferred alternative which is based on consideration of comments received from the public and agencies on the draft Hanford Defense Waste Environmental Impact Statement (HDW-EIS). Low-level waste was not included in the draft HDW-EIS whereas it is included in this plan. The preferred alternative includes disposal of double-shell tank waste, retrievably stored and newly generated TRU waste, one pre-1970 TRU solid waste site near the Columbia River and encapsulated cesium and strontium waste

Hanford Site Environmental Report 1999

International Nuclear Information System (INIS)

Poston, TM; Hanf, RW; Dirkes, RL

2000-01-01

This Hanford Site environmental report is prepared annually to summarize environmental data and information, to describe environmental management performance, to demonstrate the status of compliance with environmental regulations, and to highlight major environmental programs and efforts. The report is written to meet requirements and guidelines of the U.S. Department of Energy (DOE) and to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to: (1) describe the Hanford Site and its mission; (2) summarize the status of compliance with environmental regulations; (3) describe the environmental programs at the Hanford Site; (4) discuss the estimated radionuclide exposure to the public from 1999 Hanford Site activities; (5) present the effluent monitoring, environmental surveillance, groundwater protection and monitoring information; and (6) discuss the activities to ensure quality

Hanford Site Environmental Report 1999

Energy Technology Data Exchange (ETDEWEB)

TM Poston; RW Hanf; RL Dirkes

2000-09-28

This Hanford Site environmental report is prepared annually to summarize environmental data and information, to describe environmental management performance, to demonstrate the status of compliance with environmental regulations, and to highlight major environmental programs and efforts. The report is written to meet requirements and guidelines of the U.S. Department of Energy (DOE) and to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to: (1) describe the Hanford Site and its mission; (2) summarize the status of compliance with environmental regulations; (3) describe the environmental programs at the Hanford Site; (4) discuss the estimated radionuclide exposure to the public from 1999 Hanford Site activities; (5) present the effluent monitoring, environmental surveillance, groundwater protection and monitoring information; and (6) discuss the activities to ensure quality.

NAD and the aging process: Role in life, death and everything in between.

Science.gov (United States)

Chini, Claudia C S; Tarragó, Mariana G; Chini, Eduardo N

2017-11-05

Life as we know it cannot exist without the nucleotide nicotinamide adenine dinucleotide (NAD). From the simplest organism, such as bacteria, to the most complex multicellular organisms, NAD is a key cellular component. NAD is extremely abundant in most living cells and has traditionally been described to be a cofactor in electron transfer during oxidation-reduction reactions. In addition to participating in these reactions, NAD has also been shown to play a key role in cell signaling, regulating several pathways from intracellular calcium transients to the epigenetic status of chromatin. Thus, NAD is a molecule that provides an important link between signaling and metabolism, and serves as a key molecule in cellular metabolic sensoring pathways. Importantly, it has now been clearly demonstrated that cellular NAD levels decline during chronological aging. This decline appears to play a crucial role in the development of metabolic dysfunction and age-related diseases. In this review we will discuss the molecular mechanisms responsible for the decrease in NAD levels during aging. Since other reviews on this subject have been recently published, we will concentrate on presenting a critical appraisal of the current status of the literature and will highlight some controversial topics in the field. In particular, we will discuss the potential role of the NADase CD38 as a driver of age-related NAD decline. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Isotope partitioning for NAD-malic enzyme from Ascaris suum confirms a steady-state random kinetic mechanism

International Nuclear Information System (INIS)

Chen, C.Y.; Harris, B.G.; Cook, P.F.

1988-01-01

Isotope partitioning studies beginning with E-[ 14 C]NAD, E-[ 14 C] malate, E-[ 14 C] NAD-Mg 2+ , and E-Mg-[ 14 C]malate suggest a steady-state random mechanism for the NAD-malic enzyme. Isotope trapping beginning with E-[ 14 C]NAD and with varying concentrations of Mg 2+ and malate in the chase solution indicates that Mg 2+ is added in rapid equilibrium and must be added prior to malate for productive ternary complex formation. Equal percentage trapping from E-[ 14 C]NAD-Mg and E-Mg-[ 14 C] malate indicates the mechanism is steady-state random with equal off-rates for NAD and malate from E-NAD-Mg-malate. The off-rates for both do not change significantly in the ternary E-Mg-malate and E-NAD-Mg complexes, nor does the off-rate change for NAD from E-NAD. No trapping of malate was obtained from E-[ 14 C] malate, suggesting that this complex is nonproductive. A quantitative analysis of the data allows an estimation of values for a number of the rate constants along the reaction pathway

Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages

Science.gov (United States)

Al-Shabany, Abbas Jawad; Moody, Alan John; Foey, Andrew David; Billington, Richard Andrew

2016-01-01

Metabolism and immune responses have been shown to be closely linked and as our understanding increases, so do the intricacies of the level of linkage. NAD+ has previously been shown to regulate tumour necrosis factor-α (TNF-α) synthesis and TNF-α has been shown to regulate NAD+ homoeostasis providing a link between a pro-inflammatory response and redox status. In the present study, we have used THP-1 differentiation into pro- (M1-like) and anti- (M2-like) inflammatory macrophage subset models to investigate this link further. Pro- and anti-inflammatory macrophages showed different resting NAD+ levels and expression levels of NAD+ homoeostasis enzymes. Challenge with bacterial lipopolysaccharide, a pro-inflammatory stimulus for macrophages, caused a large, biphasic and transient increase in NAD+ levels in pro- but not anti-inflammatory macrophages that were correlated with TNF-α release and inhibition of certain NAD+ synthesis pathways blocked TNF-α release. Lipopolysaccharide stimulation also caused changes in mRNA levels of some NAD+ homoeostasis enzymes in M1-like cells. Surprisingly, despite M2-like cells not releasing TNF-α or changing NAD+ levels in response to lipopolysaccharide, they showed similar mRNA changes compared with M1-like cells. These data further strengthen the link between pro-inflammatory responses in macrophages and NAD+. The agonist-induced rise in NAD+ shows striking parallels to well-known second messengers and raises the possibility that NAD+ is acting in a similar manner in this model. PMID:26764408

Protein-bound NAD(P)H Lifetime is Sensitive to Multiple Fates of Glucose Carbon.

Science.gov (United States)

Sharick, Joe T; Favreau, Peter F; Gillette, Amani A; Sdao, Sophia M; Merrins, Matthew J; Skala, Melissa C

2018-04-03

While NAD(P)H fluorescence lifetime imaging (FLIM) can detect changes in flux through the TCA cycle and electron transport chain (ETC), it remains unclear whether NAD(P)H FLIM is sensitive to other potential fates of glucose. Glucose carbon can be diverted from mitochondria by the pentose phosphate pathway (via glucose 6-phosphate dehydrogenase, G6PDH), lactate production (via lactate dehydrogenase, LDH), and rejection of carbon from the TCA cycle (via pyruvate dehydrogenase kinase, PDK), all of which can be upregulated in cancer cells. Here, we demonstrate that multiphoton NAD(P)H FLIM can be used to quantify the relative concentrations of recombinant LDH and malate dehydrogenase (MDH) in solution. In multiple epithelial cell lines, NAD(P)H FLIM was also sensitive to inhibition of LDH and PDK, as well as the directionality of LDH in cells forced to use pyruvate versus lactate as fuel sources. Among the parameters measurable by FLIM, only the lifetime of protein-bound NAD(P)H (τ 2 ) was sensitive to these changes, in contrast to the optical redox ratio, mean NAD(P)H lifetime, free NAD(P)H lifetime, or the relative amount of free and protein-bound NAD(P)H. NAD(P)H τ 2 offers the ability to non-invasively quantify diversions of carbon away from the TCA cycle/ETC, which may support mechanisms of drug resistance.

History of Hanford Site Defense Production (Brief)

Energy Technology Data Exchange (ETDEWEB)

GERBER, M S

2001-02-01

This paper acquaints the audience with the history of the Hanford Site, America's first full-scale defense plutonium production site. The paper includes the founding and basic operating history of the Hanford Site, including World War II construction and operations, three major postwar expansions (1947-55), the peak years of production (1956-63), production phase downs (1964-the present), a brief production spurt from 1984-86, the end of the Cold War, and the beginning of the waste cleanup mission. The paper also delineates historical waste practices and policies as they changed over the years at the Hanford Site, past efforts to chemically treat, ''fractionate,'' and/or immobilize Hanford's wastes, and resulting major waste legacies that remain today. This paper presents original, primary-source research into the waste history of the Hanford Site. Finally, the paper places the current Hanford Site waste remediation endeavors in the broad context of American and world history.

History of Hanford Site Defense Production (Brief)

International Nuclear Information System (INIS)

GERBER, M.S.

2001-01-01

This paper acquaints the audience with the history of the Hanford Site, America's first full-scale defense plutonium production site. The paper includes the founding and basic operating history of the Hanford Site, including World War II construction and operations, three major postwar expansions (1947-55), the peak years of production (1956-63), production phase downs (1964-the present), a brief production spurt from 1984-86, the end of the Cold War, and the beginning of the waste cleanup mission. The paper also delineates historical waste practices and policies as they changed over the years at the Hanford Site, past efforts to chemically treat, ''fractionate,'' and/or immobilize Hanford's wastes, and resulting major waste legacies that remain today. This paper presents original, primary-source research into the waste history of the Hanford Site. Finally, the paper places the current Hanford Site waste remediation endeavors in the broad context of American and world history

The NAD+ metabolism of Leishmania, notably the enzyme nicotinamidase involved in NAD+ salvage, offers prospects for development of anti-parasite chemotherapy.

Science.gov (United States)

Michels, Paul A M; Avilán, Luisana

2011-10-01

NAD+ plays multiple, essential roles in the cell. As a cofactor in many redox reactions it is key in the cellular energy metabolism and as a substrate it participates in many reactions leading to a variety of covalent modifications of enzymes with major roles in regulation of expression and metabolism. Cells may have the ability to produce this metabolite either via alternative de novo synthesis pathways and/or by different salvage pathways. In this issue of Molecular Microbiology, Gazanion et al. (2011) demonstrate that Leishmania species can only rely on the salvage of NAD+ building blocks. One of the enzymes involved, nicotinamidase, is absent from human cells. The enzyme is important for growth of Leishmania infantum and essential for establishing an infection. The crystal structure of the parasite protein has been solved and shows prospects for design of inhibitors to be used as leads for development of new drugs. Indeed, NAD+ metabolism is currently being considered as a promising drug target in various diseases and the vulnerability of Leishmania for interference of this metabolism has been proved in previous work by the same group, by showing that administration of NAD+ precursors has detrimental effect on the pathogenic, amastigote stage of this parasite. © 2011 Blackwell Publishing Ltd.

Vascular Plants of the Hanford Site

International Nuclear Information System (INIS)

Sackschewsky, Michael R.; Downs, Janelle L.

2001-01-01

This report provides an updated listing of the vascular plants present on and near the U.S. Department of Energy Hanford Site. This document is an update of a listing of plants prepared by Sackschewdky et al. in 1992. Since that time there has been a significant increase in the botanical knowledge of the Hanford Site. The present listing is based on an examination of herbarium collections held at PNNL, at WSU-Tri Cities, WSU-Pullman, Brigham Young University, and The University of Washington, and on examination of ecological literature derived from the Hanford and Benton county areas over the last 100 years. Based on the most recent analysis, there are approximately 725 different plant species that have been documented on or around the Hanford Site. This represents an approximate 20% increase in the number of species reported within Sackschewsky et al. (1992). This listing directly supports DOE and contractor efforts to assess the potential impacts of Hanford Site operations

Hanford Patrol Academy demolition sites closure plan

Energy Technology Data Exchange (ETDEWEB)

1993-09-30

The Hanford Site is owned by the U.S. Government and operated by the U.S. Department of Energy, Richland Operations Office. Westinghouse Hanford Company is a major contractor to the U.S. Department of Energy, Richland Operations Office and serves as co-operator of the Hanford Patrol Academy Demolition Sites, the unit addressed in this paper. This document consists of a Hanford Facility Dangerous Waste Part A Permit Application, Form 3 (Revision 4), and a closure plan for the site. An explanation of the Part A Form 3 submitted with this closure plan is provided at the beginning of the Part A section. This Hanford Patrol Academy Demolition Sites Closure Plan submittal contains information current as of December 15, 1994.

List of currently classified documents relative to Hanford Production Facilities Operations originated on the Hanford Site between 1961 and 1972

Energy Technology Data Exchange (ETDEWEB)

1993-04-01

The United States Department of Energy (DOE) has declared that all Hanford plutonium production- and operations-related information generated between 1944 and 1972 is declassified. Any documents found and deemed useful for meeting Hanford Environmental Dose Reconstruction (HEDR) objectives may be declassified with or without deletions in accordance with DOE guidance by Authorized Derivative Declassifiers. The September 1992, letter report, Declassifications Requested by the Technical Steering Panel of Hanford Documents Produced 1944--1960, (PNWD-2024 HEDR UC-707), provides an important milestone toward achieving a complete listing of documents that may be useful to the HEDR Project. The attached listing of approximately 7,000 currently classified Hanford-originated documents relative to Hanford Production Facilities Operations between 1961 and 1972 fulfills TSP Directive 89-3. This list does not include such titles as the Irradiation Processing Department, Chemical Processing Department, and Hanford Laboratory Operations monthly reports generated after 1960 which have been previously declassified with minor deletions and made publicly available. Also Kaiser Engineers Hanford (KEH) Document Control determined that no KEH documents generated between January 1, 1961 and December 31, 1972 are currently classified. Titles which address work for others have not been included because Hanford Site contractors currently having custodial responsibility for these documents do not have the authority to determine whether other than their own staff have on file an appropriate need-to-know. Furthermore, these documents do not normally contain information relative to Hanford Site operations.

HANFORD SITE RIVER CORRIDOR CLEANUP

International Nuclear Information System (INIS)

BAZZELL, K.D.

2006-01-01

In 2005, the US Department of Energy (DOE) launched the third generation of closure contracts, including the River Corridor Closure (RCC) Contract at Hanford. Over the past decade, significant progress has been made on cleaning up the river shore that bordes Hanford. However, the most important cleanup challenges lie ahead. In March 2005, DOE awarded the Hanford River Corridor Closure Contract to Washington Closure Hanford (WCH), a limited liability company owned by Washington Group International, Bechtel National and CH2M HILL. It is a single-purpose company whose goal is to safely and efficiently accelerate cleanup in the 544 km 2 Hanford river corridor and reduce or eliminate future obligations to DOE for maintaining long-term stewardship over the site. The RCC Contract is a cost-plus-incentive-fee closure contract, which incentivizes the contractor to reduce cost and accelerate the schedule. At $1.9 billion and seven years, WCH has accelerated cleaning up Hanford's river corridor significantly compared to the $3.2 billion and 10 years originally estimated by the US Army Corps of Engineers. Predictable funding is one of the key features of the new contract, with funding set by contract at $183 million in fiscal year (FY) 2006 and peaking at $387 million in FY2012. Another feature of the contract allows for Washington Closure to perform up to 40% of the value of the contract and subcontract the balance. One of the major challenges in the next few years will be to identify and qualify sufficient subcontractors to meet the goal

Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

Science.gov (United States)

Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

2016-08-01

Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats.

Directory of Open Access Journals (Sweden)

Nady Braidy

2011-04-01

Full Text Available The cofactor nicotinamide adenine dinucleotide (NAD+ has emerged as a key regulator of metabolism, stress resistance and longevity. Apart from its role as an important redox carrier, NAD+ also serves as the sole substrate for NAD-dependent enzymes, including poly(ADP-ribose polymerase (PARP, an important DNA nick sensor, and NAD-dependent histone deacetylases, Sirtuins which play an important role in a wide variety of processes, including senescence, apoptosis, differentiation, and aging. We examined the effect of aging on intracellular NAD+ metabolism in the whole heart, lung, liver and kidney of female wistar rats. Our results are the first to show a significant decline in intracellular NAD+ levels and NAD:NADH ratio in all organs by middle age (i.e.12 months compared to young (i.e. 3 month old rats. These changes in [NAD(H] occurred in parallel with an increase in lipid peroxidation and protein carbonyls (o- and m- tyrosine formation and decline in total antioxidant capacity in these organs. An age dependent increase in DNA damage (phosphorylated H2AX was also observed in these same organs. Decreased Sirt1 activity and increased acetylated p53 were observed in organ tissues in parallel with the drop in NAD+ and moderate over-expression of Sirt1 protein. Reduced mitochondrial activity of complex I-IV was also observed in aging animals, impacting both redox status and ATP production. The strong positive correlation observed between DNA damage associated NAD+ depletion and Sirt1 activity suggests that adequate NAD+ concentrations may be an important longevity assurance factor.

TEMPOL increases NAD+ and improves redox imbalance in obese mice

Directory of Open Access Journals (Sweden)

Mayumi Yamato

2016-08-01

Full Text Available Continuous energy conversion is controlled by reduction–oxidation (redox processes. NAD+ and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD+ production in the ascorbic acid–glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD+/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD+/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity.

Characterization and anion exchange removal of uranium from Hanford ground water

International Nuclear Information System (INIS)

Delegard, C.H.; Weiss, R.L.; Kimura, R.T.; Law, A.G.; Routson, R.C.

1986-01-01

In February 1985, uranium concentrations increased abruptly to 0.1 kgU/m/sup 3/ in ground waters underlying a retired liquid waste disposal facility in the United States Department of Energy-Richland Operations Hanford Site. Characterization tests showed the uranium was present as an anionic carbonate complex not sorbable by Hanford sediments. The uranium was mobilized by flow from a perched zone of water caused by recent nearby cooling water disposal above an impermeable sediment layer. In a unique demonstration of the concept of ''as low as reasonably achievable,'' efforts were immediately undertaken to minimize the spread of the plume and to reduce the amount of uranium in the ground water. An anion exchange-based uranium removal process flowsheet was rapidly developed and implemented. Operational for six months, the process has treated over 30,000 m/sup 3/ of ground water and collected 94% of the uranium while producing a treated effluent that meets criteria for discharge to the soil column

Studies of lysine cyclodeaminase from Streptomyces pristinaespiralis: Insights into the complex transition NAD+ state.

Science.gov (United States)

Ying, Hanxiao; Wang, Jing; Shi, Ting; Zhao, Yilei; Wang, Xin; Ouyang, Pingkai; Chen, Kequan

2018-01-01

Lysine cyclodeaminase (LCD) catalyzes the piperidine ring formation in macrolide-pipecolate natural products metabolic pathways from a lysine substrate through a combination of cyclization and deamination. This enzyme belongs to a unique enzyme class, which uses NAD + as the catalytic prosthetic group instead of as the co-substrate. To understand the molecular details of NAD + functions in lysine cyclodeaminase, we have determined four ternary crystal structure complexes of LCD-NAD + with pipecolic acid (LCD-PA), lysine (LCD-LYS), and an intermediate (LCD-INT) as ligands at 2.26-, 2.00-, 2.17- and 1.80 Å resolutions, respectively. By combining computational studies, a NAD + -mediated "gate keeper" function involving NAD + /NADH and Arg49 that control the binding and entry of the ligand lysine was revealed, confirming the critical roles of NAD + in the substrate access process. Further, in the gate opening form, a substrate delivery tunnel between ε-carboxyl moiety of Glu264 and the α-carboxyl moiety of Asp236 was observed through a comparison of four structure complexes. The LCD structure details including NAD + -mediated "gate keeper" and substrate tunnel may assist in the exploration the NAD + function in this unique enzyme class, and in regulation of macrolide-pipecolate natural product synthesis. Copyright © 2017 Elsevier Inc. All rights reserved.

Independent AMP and NAD signaling regulates C2C12 differentiation and metabolic adaptation.

Science.gov (United States)

Hsu, Chia George; Burkholder, Thomas J

2016-12-01

The balance of ATP production and consumption is reflected in adenosine monophosphate (AMP) and nicotinamide adenine dinucleotide (NAD) content and has been associated with phenotypic plasticity in striated muscle. Some studies have suggested that AMPK-dependent plasticity may be an indirect consequence of increased NAD synthesis and SIRT1 activity. The primary goal of this study was to assess the interaction of AMP- and NAD-dependent signaling in adaptation of C2C12 myotubes. Changes in myotube developmental and metabolic gene expression were compared following incubation with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and nicotinamide mononucleotide (NMN) to activate AMPK- and NAD-related signaling. AICAR showed no effect on NAD pool or nampt expression but significantly reduced histone H3 acetylation and GLUT1, cytochrome C oxidase subunit 2 (COX2), and MYH3 expression. In contrast, NMN supplementation for 24 h increased NAD pool by 45 % but did not reduce histone H3 acetylation nor promote mitochondrial gene expression. The combination of AMP and NAD signaling did not induce further metabolic adaptation, but NMN ameliorated AICAR-induced myotube reduction. We interpret these results as indication that AMP and NAD contribute to C2C12 differentiation and metabolic adaptation independently.

The Hanford Site focus, 1994

International Nuclear Information System (INIS)

Peterson, J.M.

1994-03-01

This report describes what the Hanford Site will look like in the next two years. We offer thumbnail sketches of Hanford Site programs and the needs we are meeting through our efforts. We describe our goals, some recent accomplishments, the work we will do in fiscal year (FY) 1994, the major activities the FY 1995 budget request covers, and the economic picture in the next few years. The Hanford Site budget shows the type of work being planned. US Department of Energy (DOE) sites like the Hanford Site use documents called Activity Data Sheets to meet this need. These are building blocks that are included in the budget. Each Activity Data Sheet is a concise (usually 4 or 5 pages) summary of a piece of work funded by the DOE's Environmental Restoration and Waste Management budget. Each sheet describes a waste management or environmental restoration need over a 5-year period; related regulatory requirements and agreements; and the cost, milestones, and steps proposed to meet the need. The Hanford Site is complex and has a huge budget, and its Activity Data Sheets run to literally thousands of pages. This report summarizes the Activity Data Sheets in a less detailed and much more reader-friendly fashion

Interim Hanford Waste Management Plan

International Nuclear Information System (INIS)

1985-09-01

The September 1985 Interim Hanford Waste Management Plan (HWMP) is the third revision of this document. In the future, the HWMP will be updated on an annual basis or as major changes in disposal planning at Hanford Site require. The most significant changes in the program since the last release of this document in December 1984 include: (1) Based on studies done in support of the Hanford Defense Waste Environmental Impact Statement (HDW-EIS), the size of the protective barriers covering contaminated soil sites, solid waste burial sites, and single-shell tanks has been increased to provide a barrier that extends 30 m beyond the waste zone. (2) As a result of extensive laboratory development and plant testing, removal of transuranic (TRU) elements from PUREX cladding removal waste (CRW) has been initiated in PUREX. (3) The level of capital support in years beyond those for which specific budget projections have been prepared (i.e., fiscal year 1992 and later) has been increased to maintain Hanford Site capability to support potential future missions, such as the extension of N Reactor/PUREX operations. The costs for disposal of Hanford Site defense wastes are identified in four major areas in the HWMP: waste storage and surveillance, technology development, disposal operations, and capital expenditures

Third Quarter Hanford Seismic Report for Fiscal Year 2005

Energy Technology Data Exchange (ETDEWEB)

Reidel, Steve P.; Rohay, Alan C.; Hartshorn, Donald C.; Clayton, Ray E.; Sweeney, Mark D.

2005-09-01

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 41 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. For the Hanford Seismic Network, there were 337 triggers during the third quarter of fiscal year 2005. Of these triggers, 20 were earthquakes within the Hanford Seismic Network. The largest earthquake within the Hanford Seismic Network was a magnitude 1.3 event May 25 near Vantage, Washington. During the third quarter, stratigraphically 17 (85%) events occurred in the Columbia River basalt (approximately 0-5 km), no events in the pre-basalt sediments (approximately 5-10 km), and three (15%) in the crystalline basement (approximately 10-25 km). During the first quarter, geographically five (20%) earthquakes occurred in swarm areas, 10 (50%) earthquakes were associated with a major geologic structure, and 5 (25%) were classified as random events.

NADS: A Web Applet for Manipulation and Graphical Viewing of Nuclear Data

International Nuclear Information System (INIS)

McKinley, M S; Beck, B R; McNabb, D P

2004-01-01

We have developed a program called NADS (Nuclear and Atomic Data System) which provides a web-based, user-friendly interface for viewing nuclear data. NADS uses a client/server model. The client is a Java applet that runs in a web browser. The server is a Python code that delivers pointwise data to the applet per user request and then plots the data. The data is also stored in tables for viewing and modifying. NADS can display 2-D, 3-D and 4-D (time sliced) data in a powerful, user-friendly environment. Currently, evaluated nuclear data are available from ENDF/B-V, ENDF/B-VI, JENDL, JEF and Lawrence Livermore National Laboratory's ENDL databases. LLNL's ENDL database has data for neutron, gamma and charged particles as projectiles. In addition to displaying and saving data, NADS has the capability to perform computations with the data. NADS is accessible over the Internet at http://nuclear.llnl.gov/

Dunnione ameliorates cisplatin ototoxicity through modulation of NAD(+) metabolism.

Science.gov (United States)

Kim, Hyung-Jin; Pandit, Arpana; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon; Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young; Kwak, Tae Hwan; Choe, Seong-Kyu; Park, Raekil; So, Hong-Seob

2016-03-01

Ototoxicity is an important issue in patients receiving cisplatin chemotherapy. Numerous studies have demonstrated that cisplatin-induced ototoxicity is related to oxidative stress and DNA damage. However, the precise mechanism underlying cisplatin-associated ototoxicity is still unclear. The cofactor nicotinamide adenine dinucleotide (NAD(+)) has emerged as an important regulator of energy metabolism and cellular homeostasis. Here, we demonstrate that the levels and activities of sirtuin-1 (SIRT1) are suppressed by the reduction of intracellular NAD(+) levels in cisplatin-mediated ototoxicity. We provide evidence that the decreases in SIRT1 activity and expression facilitated by increasing poly(ADP-ribose) polymerase-1 (PARP-1) activation and microRNA-34a levels through cisplatin-mediated p53 activation aggravate the associated ototoxicity. Furthermore, we show that the induction of cellular NAD(+) levels using dunnione, which targets intracellular NQO1, prevents the toxic effects of cisplatin through the regulation of PARP-1 and SIRT1 activity. These results suggest that direct modulation of cellular NAD(+) levels by pharmacological agents could be a promising therapeutic approach for protection from cisplatin-induced ototoxicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Hanford Site Environmental Report 1993

Energy Technology Data Exchange (ETDEWEB)

Dirkes, R.L.; Hanf, R.W.; Woodruff, R.K. [eds.

1994-06-01

The Hanford Site Environmental Report is prepared annually to summarize environmental data and information, describe environmental management performance, and demonstrate the status of compliance with environmental regulations. The report also highlights major environmental programs and efforts. The report is written to meet reporting requirements and Guidelines of the U.S. Department of Energy (DOE) an to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to (a) describe the Hanford Site and its mission, (b) summarize the status in 1993 of compliance with environmental regulations, (c) describe the environmental programs at the Hanford Site, (d) discuss estimated radionuclide exposure to the public from 1993 Hanford activities, (e) present information on effluent monitoring and environmental surveillance, including ground-water protection and monitoring, (f) discuss activities to ensure quality. More detailed information can be found in the body of the report, the appendixes, and the cited references.

Hanford Site Environmental Report 1993

International Nuclear Information System (INIS)

Dirkes, R.L.; Hanf, R.W.; Woodruff, R.K.

1994-06-01

The Hanford Site Environmental Report is prepared annually to summarize environmental data and information, describe environmental management performance, and demonstrate the status of compliance with environmental regulations. The report also highlights major environmental programs and efforts. The report is written to meet reporting requirements and Guidelines of the U.S. Department of Energy (DOE) an to meet the needs of the public. This summary has been written with a minimum of technical terminology. Individual sections of the report are designed to (a) describe the Hanford Site and its mission, (b) summarize the status in 1993 of compliance with environmental regulations, (c) describe the environmental programs at the Hanford Site, (d) discuss estimated radionuclide exposure to the public from 1993 Hanford activities, (e) present information on effluent monitoring and environmental surveillance, including ground-water protection and monitoring, (f) discuss activities to ensure quality. More detailed information can be found in the body of the report, the appendixes, and the cited references

Hanford Area 2000 Population

International Nuclear Information System (INIS)

Elliott, Douglas B.; Scott, Michael J.; Antonio, Ernest J.; Rhoads, Kathleen

2004-01-01

This report was prepared for the U.S. Department of Energy (DOE) Richland Operations Office, Surface Environmental Surveillance Project, to provide demographic data required for ongoing environmental assessments and safety analyses at the DOE Hanford Site near Richland, Washington. This document includes 2000 Census estimates for the resident population within an 80-kilometer (50-mile) radius of the Hanford Site. Population distributions are reported relative to five reference points centered on meteorological stations within major operating areas of the Hanford Site - the 100 F, 100 K, 200, 300, and 400 Areas. These data are presented in both graphical and tabular format, and are provided for total populations residing within 80 km (50 mi) of the reference points, as well as for Native American, Hispanic and Latino, total minority, and low-income populations

Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing

Science.gov (United States)

Zhou, Can‐Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao‐Bing; Li, Guo‐Qiang; Song, Jie; Xu, Tian‐Ying; Li, Zhi‐Yong; Guan, Yun‐Feng

2016-01-01

Abstract Background and Purpose Ageing is an important risk factor of non‐alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD+), a ubiquitous coenzyme, links ageing with NAFLD. Experimental Approach Hepatic concentrations of NAD+, protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD+ biosynthesis, were compared in middle‐aged and aged mice or patients. The influences of NAD+ decline on the steatosis and steatohepatitis were evaluated in wild‐type and H247A dominant‐negative, enzymically‐inactive NAMPT transgenic mice (DN‐NAMPT) given normal or high‐fat diet (HFD). Key Results Hepatic NAD+ level decreased in aged mice and humans. NAMPT‐controlled NAD+ salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle‐age DN‐NAMPT mice displayed systemic NAD+ reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro‐inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α‐SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD+ precursor, completely corrected these NAFLD phenotypes induced by NAD+ deficiency alone or HFD, whereas adenovirus‐mediated SIRT1 overexpression only partially rescued these phenotypes. Conclusions and Implications These results provide the first evidence that ageing‐associated NAD+ deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD+ substrates may be a promising therapeutic strategy to prevent and treat NAFLD. PMID:27174364

Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

Science.gov (United States)

Xiao, Yang; Kwong, Mandy; Daemen, Anneleen; Belvin, Marcia; Liang, Xiaorong; Hatzivassiliou, Georgia; O'Brien, Thomas

2016-01-01

Nicotinamide adenine dinucleotide (NAD) is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM) to nicotinamide mononucleotide (NMN), the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334), one that shows intermediate sensitivity (NCI-H441), and one that is insensitive (LC-KJ). Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP) and had lower reactive oxygen species (ROS) levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

Metabolic Response to NAD Depletion across Cell Lines Is Highly Variable.

Directory of Open Access Journals (Sweden)

Yang Xiao

Full Text Available Nicotinamide adenine dinucleotide (NAD is a cofactor involved in a wide range of cellular metabolic processes and is a key metabolite required for tumor growth. NAMPT, nicotinamide phosphoribosyltransferase, which converts nicotinamide (NAM to nicotinamide mononucleotide (NMN, the immediate precursor of NAD, is an attractive therapeutic target as inhibition of NAMPT reduces cellular NAD levels and inhibits tumor growth in vivo. However, there is limited understanding of the metabolic response to NAD depletion across cancer cell lines and whether all cell lines respond in a uniform manner. To explore this we selected two non-small cell lung carcinoma cell lines that are sensitive to the NAMPT inhibitor GNE-617 (A549, NCI-H1334, one that shows intermediate sensitivity (NCI-H441, and one that is insensitive (LC-KJ. Even though NAD was reduced in all cell lines there was surprising heterogeneity in their metabolic response. Both sensitive cell lines reduced glycolysis and levels of di- and tri-nucleotides and modestly increased oxidative phosphorylation, but they differed in their ability to combat oxidative stress. H1334 cells activated the stress kinase AMPK, whereas A549 cells were unable to activate AMPK as they contain a mutation in LKB1, which prevents activation of AMPK. However, A549 cells increased utilization of the Pentose Phosphate pathway (PPP and had lower reactive oxygen species (ROS levels than H1334 cells, indicating that A549 cells are better able to modulate an increase in oxidative stress. Inherent resistance of LC-KJ cells is associated with higher baseline levels of NADPH and a delayed reduction of NAD upon NAMPT inhibition. Our data reveals that cell lines show heterogeneous response to NAD depletion and that the underlying molecular and genetic framework in cells can influence the metabolic response to NAMPT inhibition.

Ferrocyanide Safety Program: Safety criteria for ferrocyanide watch list tanks

International Nuclear Information System (INIS)

Postma, A.K.; Meacham, J.E.; Barney, G.S.

1994-01-01

This report provides a technical basis for closing the ferrocyanide Unreviewed Safety Question (USQ) at the Hanford Site. Three work efforts were performed in developing this technical basis. The efforts described herein are: 1. The formulation of criteria for ranking the relative safety of waste in each ferrocyanide tank. 2. The current classification of tanks into safety categories by comparing available information on tank contents with the safety criteria; 3. The identification of additional information required to resolve the ferrocyanide safety issue

Hanford site transuranic waste sampling plan

International Nuclear Information System (INIS)

GREAGER, T.M.

1999-01-01

This sampling plan (SP) describes the selection of containers for sampling of homogeneous solids and soil/gravel and for visual examination of transuranic and mixed transuranic (collectively referred to as TRU) waste generated at the U.S. Department of Energy (DOE) Hanford Site. The activities described in this SP will be conducted under the Hanford Site TRU Waste Certification Program. This SP is designed to meet the requirements of the Transuranic Waste Characterization Quality Assurance Program Plan (CAO-94-1010) (DOE 1996a) (QAPP), site-specific implementation of which is described in the Hanford Site Transuranic Waste Characterization Program Quality Assurance Project Plan (HNF-2599) (Hanford 1998b) (QAPP). The QAPP defines the quality assurance (QA) requirements and protocols for TRU waste characterization activities at the Hanford Site. In addition, the QAPP identifies responsible organizations, describes required program activities, outlines sampling and analysis strategies, and identifies procedures for characterization activities. The QAPP identifies specific requirements for TRU waste sampling plans. Table 1-1 presents these requirements and indicates sections in this SP where these requirements are addressed

Muscle type-specific responses to NAD+ salvage biosynthesis promote muscle function in Caenorhabditis elegans.

Science.gov (United States)

Vrablik, Tracy L; Wang, Wenqing; Upadhyay, Awani; Hanna-Rose, Wendy

2011-01-15

Salvage biosynthesis of nicotinamide adenine dinucleotide (NAD(+)) from nicotinamide (NAM) lowers NAM levels and replenishes the critical molecule NAD(+) after it is hydrolyzed. This pathway is emerging as a regulator of multiple biological processes. Here we probe the contribution of the NAM-NAD(+) salvage pathway to muscle development and function using Caenorhabditis elegans. C. elegans males with mutations in the nicotinamidase pnc-1, which catalyzes the first step of this NAD(+) salvage pathway, cannot mate due to a spicule muscle defect. Multiple muscle types are impaired in the hermaphrodites, including body wall muscles, pharyngeal muscles and vulval muscles. An active NAD(+) salvage pathway is required for optimal function of each muscle cell type. However, we found surprising muscle-cell-type specificity in terms of both the timing and relative sensitivity to perturbation of NAD(+) production or NAM levels. Active NAD(+) biosynthesis during development is critical for function of the male spicule protractor muscles during adulthood, but these muscles can surprisingly do without salvage biosynthesis in adulthood under the conditions examined. The body wall muscles require ongoing NAD(+) salvage biosynthesis both during development and adulthood for maximum function. The vulval muscles do not function in the presence of elevated NAM concentrations, but NAM supplementation is only slightly deleterious to body wall muscles during development or upon acute application in adults. Thus, the pathway plays distinct roles in different tissues. As NAM-NAD(+) biosynthesis also impacts muscle differentiation in vertebrates, we propose that similar complexities may be found among vertebrate muscle cell types. Copyright © 2010 Elsevier Inc. All rights reserved.

NADS - Nuclear and Atomic Data System

International Nuclear Information System (INIS)

McKinley, Michael S.; Beck, Bret; McNabb, Dennis

2005-01-01

We have developed NADS (Nuclear and Atomic Data System), a web-based graphical interface for viewing pointwise and grouped cross sections and distributions. Our implementation is a client / server model. The client is a Java applet that displays the graphical interface, which has interactive 2-D, 3-D, and 4-D plots and tables. The server, which can serve and perform computations of the data, has been implemented in Python using the FUDGE package developed by Bret Beck at LLNL. Computational capabilities include algebraic manipulation of nuclear evaluated data in databases such as LLNL's ENDL-99, ENDF/B-V, and ENDF/B-VI, as well as user data. Processed data used in LLNL's transport codes are accessible as well. NADS is available from http://nuclear.llnl.gov/

Ultra-fast HPM detectors improve NAD(P)H FLIM

Science.gov (United States)

Becker, Wolfgang; Wetzker, Cornelia; Benda, Aleš

2018-02-01

Metabolic imaging by NAD(P)H FLIM requires the decay functions in the individual pixels to be resolved into the decay components of bound and unbound NAD(P)H. Metabolic information is contained in the lifetime and relative amplitudes of the components. The separation of the decay components and the accuracy of the amplitudes and lifetimes improves substantially by using ultra-fast HPM-100-06 and HPM-100-07 hybrid detectors. The IRF width in combination with the Becker & Hickl SPC-150N and SPC-150NX TCSPC modules is less than 20 ps. An IRF this fast does not interfere with the fluorescence decay. The usual deconvolution process in the data analysis then virtually becomes a simple curve fitting, and the parameters of the NAD(P)H decay components are obtained at unprecedented accuracy.

Hanford inventory program user's manual

International Nuclear Information System (INIS)

Hinkelman, K.C.

1994-01-01

Provides users with instructions and information about accessing and operating the Hanford Inventory Program (HIP) system. The Hanford Inventory Program is an integrated control system that provides a single source for the management and control of equipment, parts, and material warehoused by Westinghouse Hanford Company in various site-wide locations. The inventory is comprised of spare parts and equipment, shop stock, special tools, essential materials, and convenience storage items. The HIP replaced the following systems; ACA, ASP, PICS, FSP, WSR, STP, and RBO. In addition, HIP manages the catalog maintenance function for the General Supplies inventory stocked in the 1164 building and managed by WIMS

Struktuur en interaktie analyse van NAD+ en NAD+ analoga in horse liver alcohol dehydrogenase

NARCIS (Netherlands)

Beijer, N.A.

1988-01-01

Dit verslag beschrijft een studie naar de relatie tussen struktuur en funktie voor het co-enzym NAn+ en zijn analoga in de aktieve holte van het enzym Horse Liver Alcohol Dehydrogenase (LADH). De rol van NAD+ in enzymgekatalyseerde oxidatie-reduktie reakties is die van het bewerkstelligen van een

Novel concept of enzyme selective nicotinamide adenine dinucleotide (NAD)-modified inhibitors based on enzyme taxonomy from the diphosphate conformation of NAD.

Science.gov (United States)

Fujii, Mikio; Kitagawa, Yasuyuki; Iida, Shui; Kato, Keisuke; Ono, Machiko

2015-11-15

The dihedral angle θ of the diphosphate part of NAD(P) were investigated to distinguish the differences in the binding-conformation of NAD(P) to enzymes and to create an enzyme taxonomy. Furthermore, new inhibitors with fixed dihedral angles showed that enzymes could recognize the differences in the dihedral angle θ. We suggest the taxonomy and the dihedral angle θ are important values for chemists to consider when designing inhibitors and drugs that target enzymes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hanford Site Composite Analysis Technical Approach Description: Hanford Site Disposition Baseline.

Energy Technology Data Exchange (ETDEWEB)

Cobb, M. A. [CH2M HILL Plateau Remediation Company, Richland, WA (United States); Dockter, R. E. [CH2M HILL Plateau Remediation Company, Richland, WA (United States)

2017-10-02

The permeability of ground surfaces within the U.S. Department of Energy’s (DOE) Hanford Site strongly influences boundary conditions when simulating the movement of groundwater using the Subsurface Transport Over Multiple Phases model. To conduct site-wide modeling of cumulative impacts to groundwater from past, current, and future waste management activities, a site-wide assessment of the permeability of surface conditions is needed. The surface condition of the vast majority of the Hanford Site has been and continues to be native soils vegetated with dryland grasses and shrubs.

Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

Energy Technology Data Exchange (ETDEWEB)

Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J. (Medical College of Wisconsin, Milwaukee (USA))

1989-11-01

UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from (3H-nicotinamide)NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from (32P-adenylate)NAD (0.2 mol/mol of protein). Label from (3H-nicotinamide)NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with (3H-nicotinamide)NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis.

Photolabeling of Glu-129 of the S-1 subunit of pertussis toxin with NAD

International Nuclear Information System (INIS)

Barbieri, J.T.; Mende-Mueller, L.M.; Rappuoli, R.; Collier, R.J.

1989-01-01

UV irradiation was shown to induce efficient transfer of radiolabel from nicotinamide-labeled NAD to a recombinant protein (C180 peptide) containing the catalytic region of the S-1 subunit of pertussis toxin. Incorporation of label from [3H-nicotinamide]NAD was efficient (0.5 to 0.6 mol/mol of protein) relative to incorporation from [32P-adenylate]NAD (0.2 mol/mol of protein). Label from [3H-nicotinamide]NAD was specifically associated with Glu-129. Replacement of Glu-129 with glycine or aspartic acid made the protein refractory to photolabeling with [3H-nicotinamide]NAD, whereas replacement of a nearby glutamic acid, Glu-139, with serine did not. Photolabeling of the C180 peptide with NAD is similar to that observed with diphtheria toxin and exotoxin A of Pseudomonas aeruginosa, in which the nicotinamide portion of NAD is transferred to Glu-148 and Glu-553, respectively, in the two toxins. These results implicate Glu-129 of the S-1 subunit as an active-site residue and a potentially important site for genetic modification of pertussis toxin for development of an acellular vaccine against Bordetella pertussis

Structure of a NAD kinase from Thermotoga maritima at 2.3 Å resolution

International Nuclear Information System (INIS)

Oganesyan, Vaheh; Huang, Candice; Adams, Paul D.; Jancarik, Jaru; Yokota, Hisao A.; Kim, Rosalind; Kim, Sung-Hou

2005-01-01

The expression, purification, crystallization, and structure determination of NAD-kinase from T. maritima are reported. Similarity to other NAD-kinases as well as homo-oligomrization state of the enzyme from T. maritima are discussed. NAD kinase is the only known enzyme that catalyzes the formation of NADP, a coenzyme involved in most anabolic reactions and in the antioxidant defense system. Despite its importance, very little is known regarding the mechanism of catalysis and only recently have several NAD kinase structures been deposited in the PDB. Here, an independent investigation of the crystal structure of inorganic polyphosphate/ATP-NAD kinase, PPNK-THEMA, a protein from Thermotoga maritima, is reported at a resolution of 2.3 Å. The crystal structure was solved using single-wavelength anomalous diffraction (SAD) data collected at the Se absorption-peak wavelength in a state in which no cofactors or substrates were bound. It revealed that the 258-amino-acid protein is folded into two distinct domains, similar to recently reported NAD kinases. The N-terminal α/β-domain spans the first 100 amino acids and the last 30 amino acids of the polypeptide and has several topological matches in the PDB, whereas the other domain, which spans the middle 130 residues, adopts a unique β-sandwich architecture and only appreciably matches the recently deposited PDB structures of NAD kinases

Annual Hanford Seismic Report for Fiscal Year 2008

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2008-12-29

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The HSAP is responsible for locating and identifying sources of seismic activity and monitoring changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the HSAP works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. During fiscal year 2008, the Hanford Seismic Network recorded 1431 triggers on the seismometer system, which included 112 seismic events in the southeast Washington area and an additional 422 regional and teleseismic events. There were 74 events determined to be local earthquakes relevant to the Hanford Site. The highest-magnitude event (3.7 Mc) occurred on May 18, 2008, and was located approximately 17 km east of Prosser at a depth of 20.5 km. With regard to the depth distribution, 13 earthquakes were located at shallow depths (less than 4 km, most likely in the Columbia River basalts), 45 earthquakes were located at intermediate depths (between 4 and 9 km, most likely in the pre-basalt sediments), and 16 earthquakes were located at depths greater than 9 km, within the crystalline basement. Geographically, 54 earthquakes were located in swarm areas and 20 earthquakes were classified as random events. The May 18 earthquake was the highest magnitude event recorded since 1975 in the vicinity of the Hanford Site (between 46 degrees and 47 degrees north latitude and

Engineering Task Plan for the Ultrasonic Inspection of Hanford Double Shell Tanks (DST) FY2000

International Nuclear Information System (INIS)

JENSEN, C.E.

2000-01-01

This document facilitates the ultrasonic examination of Hanford double-shell tanks. Included are a plan for engineering activities (individual responsibilities), plan for performance demonstration testing, and a plan for field activities (tank inspection). Also included are a Statement of Work for contractor performance of the work and a protocol to be followed should tank flaws that exceed the acceptance criteria be discovered

Hanford annual second quarter seismic report, fiscal year 1998: Seismicity on and near the Hanford Site, Pasco, Washington

Energy Technology Data Exchange (ETDEWEB)

Hartshorn, D.C.; Reidel, S.P.; Rohay, A.C.

1998-06-01

Hanford Seismic Monitoring provides an uninterrupted collection of high quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the US Department of Energy and its contractors. The staff also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of an earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (ENN) consist of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The operational rate for the second quarter of FY98 for stations in the HSN was 99.92%. The operational rate for the second quarter of FY98 for stations of the EWRN was 99.46%. For the second quarter of FY98, the acquisition computer triggered 159 times. Of these triggers 14 were local earthquakes: 7 (50%) in the Columbia River Basalt Group, 3 (21%) in the pre-basalt sediments, and 4 (29%) in the crystalline basement. The geologic and tectonic environments where these earthquakes occurred are discussed in this report. The most significant seismic event for the second quarter was on March 23, 1998 when a 1.9 Mc occurred near Eltopia, WA and was felt by local residents. Although this was a small event, it was felt at the surface and is an indication of the potential impact on Hanford of seismic events that are common to the Site.

Historical research in the Hanford site waste cleanup

International Nuclear Information System (INIS)

Gerber, Michele S.

1992-01-01

This paper will acquaint the audience with role of historical research in the Hanford Site waste cleanup - the largest waste cleanup endeavor ever undertaken in human history. There were no comparable predecessors to this massive waste remediation effort, but the Hanford historical record can provide a partial road map and guide. It can be, and is, a useful tool in meeting the goal of a successful, cost-effective, safe and technologically exemplary waste cleanup. The Hanford historical record is rich and complex. Yet, it poses difficult challenges, in that no central and complete repository or data base exists, records contain obscure code words and code numbers, and the measurement systems and terminology used in the records change many times over the years. Still, these records are useful to the current waste cleanup in technical ways, and in ways that extend beyond a strictly scientific aspect. Study and presentations of Hanford Site history contribute to the huge educational and outreach tasks of helping the Site's work force deal with 'culture change' and become motivated for the cleanup work that is ahead, and of helping the public and the regulators to place the events at Hanford in the context of WWII and the Cold War. This paper traces historical waste practices and policies as they changed over the years at the Hanford Site, and acquaints the audience with the generation of the major waste streams of concern in Hanford Site cleanup today. It presents original, primary-source research into the waste history of the Hanford Site. The earliest, 1940s knowledge base, assumptions and calculations about radioactive and chemical discharges, as discussed in the memos, correspondence and reports of the original Hanford Site (then Hanford Engineer Works) builders and operators, are reviewed. The growth of knowledge, research efforts, and subsequent changes in Site waste disposal policies and practices are traced. Examples of the strengths and limitations of the

In vitro metabolic engineering for the salvage synthesis of NAD(.).

Science.gov (United States)

Honda, Kohsuke; Hara, Naoya; Cheng, Maria; Nakamura, Anna; Mandai, Komako; Okano, Kenji; Ohtake, Hisao

2016-05-01

Excellent thermal and operational stabilities of thermophilic enzymes can greatly increase the applicability of biocatalysis in various industrial fields. However, thermophilic enzymes are generally incompatible with thermo-labile substrates, products, and cofactors, since they show the maximal activities at high temperatures. Despite their pivotal roles in a wide range of enzymatic redox reactions, NAD(P)(+) and NAD(P)H exhibit relatively low stabilities at high temperatures, tending to be a major obstacle in the long-term operation of biocatalytic chemical manufacturing with thermophilic enzymes. In this study, we constructed an in vitro artificial metabolic pathway for the salvage synthesis of NAD(+) from its degradation products by the combination of eight thermophilic enzymes. The enzymes were heterologously produced in recombinant Escherichia coli and the heat-treated crude extracts of the recombinant cells were directly used as enzyme solutions. When incubated with experimentally optimized concentrations of the enzymes at 60°C, the NAD(+) concentration could be kept almost constant for 15h. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Mortality studies of Hanford workers

International Nuclear Information System (INIS)

Gilbert, E.S.

1986-04-01

Radiation exposures at Hanford have been deliberately limited as a protection to the worker. This means that if current estimates of radiation risks, which have been determined by national and international groups, are correct, it's highly unlikely that noticeable radiation-induced health effects will be identified among Hanford workers. 1 fig., 4 tabs

NAD+ protects against EAE by regulating CD4+ T-cell differentiation

Science.gov (United States)

Tullius, Stefan G.; Biefer, Hector Rodriguez Cetina; Li, Suyan; Trachtenberg, Alexander J.; Edtinger, Karoline; Quante, Markus; Krenzien, Felix; Uehara, Hirofumi; Yang, Xiaoyong; Kissick, Haydn T.; Kuo, Winston P.; Ghiran, Ionita; de la Fuente, Miguel A.; Arredouani, Mohamed S.; Camacho, Virginia; Tigges, John C.; Toxavidis, Vasilis; El Fatimy, Rachid; Smith, Brian D.; Vasudevan, Anju; ElKhal, Abdallah

2014-01-01

CD4+ T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD+) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4+IFNγ+IL-10+ T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD+ regulates CD4+ T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD+, the frequency of T-bet−/− CD4+IFNγ+ T cells was twofold higher than wild-type CD4+ T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4+ T-cell differentiation and demonstrate that NAD+ may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases. PMID:25290058

Hanford's Radioactive Mixed Waste Disposal Facility

International Nuclear Information System (INIS)

McKenney, D.E.

1995-01-01

The Radioactive Mixed Waste Disposal Facility, is located in the Hanford Site Low-Level Burial Grounds and is designated as Trench 31 in the 218-W-5 Burial Ground. Trench 31 is a Resource Conservation and Recovery Act compliant landfill and will receive wastes generated from both remediation and waste management activities. On December 30, 1994, Westinghouse Hanford Company declared readiness to operate Trench 31, which is the Hanford Site's (and the Department of Energy complex's) first facility for disposal of low-level radioactive mixed wastes

Hanford cultural resources laboratory

Energy Technology Data Exchange (ETDEWEB)

Wright, M.K.

1995-06-01

This section of the 1994 Hanford Site Environmental Report describes activities of the Hanford Cultural Resources Laboratory (HCRL) which was established by the Richland Operations Office in 1987 as part of PNL.The HCRL provides support for the management of the archaeological, historical, and traditional cultural resources of the site in a manner consistent with the National Historic Preservation Act, the Native American Graves Protection and Repatriation Act, and the American Indian Religious Freedom Act.

Hanford cultural resources laboratory

International Nuclear Information System (INIS)

Wright, M.K.

1995-01-01

This section of the 1994 Hanford Site Environmental Report describes activities of the Hanford Cultural Resources Laboratory (HCRL) which was established by the Richland Operations Office in 1987 as part of PNL.The HCRL provides support for the management of the archaeological, historical, and traditional cultural resources of the site in a manner consistent with the National Historic Preservation Act, the Native American Graves Protection and Repatriation Act, and the American Indian Religious Freedom Act

Hanford work faces change

International Nuclear Information System (INIS)

Anon.

1992-01-01

This article is a discussion of DOE efforts in the awarding of a large engineering-construction contract at the Hanford Reservation. Though the announced winner was a group lead by J. A. Jones Construction/Duke Engineering Services, the incumbent (ICF-Kaiser Engineers) protested the announced award. The protest was dismissed by the GAO, but DOE officials still reopened the bidding. There was also a short note regarding the award of the ERMC at Hanford

Annual Hanford seismic report - fiscal year 1996

International Nuclear Information System (INIS)

Hartshorn, D.C.; Reidel, S.P.

1996-12-01

Seismic monitoring (SM) at the Hanford Site was established in 1969 by the US Geological Survey (USGS) under a contract with the US Atomic Energy Commission. Since 1980, the program has been managed by several contractors under the US Department of Energy (USDOE). Effective October 1, 1996, the Seismic Monitoring workscope, personnel, and associated contracts were transferred to the USDOE Pacific Northwest National Laboratory (PNNL). SM is tasked to provide an uninterrupted collection and archives of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) located on and encircling the Hanford Site. SM is also tasked to locate and identify sources of seismic activity and monitor changes in the historical pattern of seismic activity at the Hanford Site. The data compiled are used by SM, Waste Management, and engineering activities at the Hanford Site to evaluate seismic hazards and seismic design for the Site

Isonicotinamide Enhances Sir2 Protein-mediated Silencing and Longevity in Yeast by Raising Intracellular NAD+ Concentration*

Science.gov (United States)

McClure, Julie M.; Wierman, Margaret B.; Maqani, Nazif; Smith, Jeffrey S.

2012-01-01

Sirtuins are an evolutionarily conserved family of NAD+-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD+ concentration through the combined action of NAD+ biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD+ precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD+ salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD+ concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD+. The INAM-induced increase in NAD+ was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD+ salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD+. We also provide evidence suggesting that INAM influences the expression of multiple NAD+ biosynthesis and salvage pathways to promote homeostasis during stationary phase. PMID:22539348

Isonicotinamide enhances Sir2 protein-mediated silencing and longevity in yeast by raising intracellular NAD+ concentration.

Science.gov (United States)

McClure, Julie M; Wierman, Margaret B; Maqani, Nazif; Smith, Jeffrey S

2012-06-15

Sirtuins are an evolutionarily conserved family of NAD(+)-dependent protein deacetylases that function in the regulation of gene transcription, cellular metabolism, and aging. Their activity requires the maintenance of an adequate intracellular NAD(+) concentration through the combined action of NAD(+) biosynthesis and salvage pathways. Nicotinamide (NAM) is a key NAD(+) precursor that is also a byproduct and feedback inhibitor of the deacetylation reaction. In Saccharomyces cerevisiae, the nicotinamidase Pnc1 converts NAM to nicotinic acid (NA), which is then used as a substrate by the NAD(+) salvage pathway enzyme NA phosphoribosyltransferase (Npt1). Isonicotinamide (INAM) is an isostere of NAM that stimulates yeast Sir2 deacetylase activity in vitro by alleviating the NAM inhibition. In this study, we determined that INAM stimulates Sir2 through an additional mechanism in vivo, which involves elevation of the intracellular NAD(+) concentration. INAM enhanced normal silencing at the rDNA locus but only partially suppressed the silencing defects of an npt1Δ mutant. Yeast cells grown in media lacking NA had a short replicative life span, which was extended by INAM in a SIR2-dependent manner and correlated with increased NAD(+). The INAM-induced increase in NAD(+) was strongly dependent on Pnc1 and Npt1, suggesting that INAM increases flux through the NAD(+) salvage pathway. Part of this effect was mediated by the NR salvage pathways, which generate NAM as a product and require Pnc1 to produce NAD(+). We also provide evidence suggesting that INAM influences the expression of multiple NAD(+) biosynthesis and salvage pathways to promote homeostasis during stationary phase.

United States Stateplane Zones - NAD83

Data.gov (United States)

Earth Data Analysis Center, University of New Mexico — U.S. State Plane Zones (NAD 1983) represents the State Plane Coordinate System (SPCS) Zones for the 1983 North American Datum within United States.

United States Stateplane Zones - NAD27

Data.gov (United States)

Earth Data Analysis Center, University of New Mexico — U.S. State Plane Zones (NAD 1927) represents the State Plane Coordinate System (SPCS) Zones for the 1927 North American Datum within United States.

VT NAD83 Orthophoto Boundaries - polygons

Data.gov (United States)

Vermont Center for Geographic Information — (Link to Metadata) RF 5000 NAD83 orthophoto edge lines (4000 x 4000 meter grid cells) were generated automatically from the known corner locations (generated by Gary...

Field trip guide to the Hanford Site

International Nuclear Information System (INIS)

Reidel, S.P.; Lindsey, K.A.; Fecht, K.R.

1992-11-01

This report is designed to provide a guide to the key geologic and hydrologic features of the US Department of Energy's Hanford Site located in south-central Washington. The guide is divided into two parts. The first part is a general introduction to the geology of the Hanford Site and its relation to the regional framework of south-central Washington. The second part is a road log that provides directions to important geologic features on the Hanford Site and descriptions of the locality. The exposures described were chosen for their accessibility and importance to the geologic history of the Hanford Site and to understanding the geohydrology of the Site

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

International Nuclear Information System (INIS)

Rathbone, Bruce A.

2006-01-01

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at Hanford. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with 10 CFR 835, DOELAP, DOE-RL, ORP, PNSO, and Hanford contractor requirements. The dosimetry system is operated by PNNL's Hanford External Dosimetry Program which provides dosimetry services to all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. Rev. 0 marks the first revision to be released through PNNL's Electronic Records & Information Capture Architecture (ERICA) database

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

Energy Technology Data Exchange (ETDEWEB)

Rathbone, Bruce A.

2005-02-25

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at Hanford. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with 10 CFR 835, DOELAP, DOE-RL, ORP, PNSO, and Hanford contractor requirements. The dosimetry system is operated by PNNL’s Hanford External Dosimetry Program which provides dosimetry services to all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. Rev. 0 marks the first revision to be released through PNNL’s Electronic Records & Information Capture Architecture (ERICA) database.

Hanford Site Performance Report - March 1999

International Nuclear Information System (INIS)

EDER, D.M.

2001-01-01

The purpose of the Hanford Site Performance Report is to provide the Department of Energy Richland Operations Office's (DOE-RL's) report of Hanford's performance by: U.S. Department of Energy, Richland Operations Office, Project Hanford Management Contract (PHMC) through Fluor Daniel Hanford, Inc. (FDH) and its subcontractors, Environmental Restoration Contract through Bechtel Hanford, Inc. (BHI), and its subcontractors, and Pacific Northwest National Laboratories (PNNL) for Science and Technology (S and T) Mission and support to the Environmental Management (EM). This report is published monthly with the intent of relating work performance and progress in the context of the Success Indicators and Critical Success Factors as outlined in the Hanford Strategic Plan. On a quarterly basis, the report also addresses performance and progress related to the Science and Technology Mission's Critical Outcomes as derived from the Hanford Strategic Plan. Section A of this report is the Executive Summary, encapsulating high-level data in this report into an overall brief. Summary information provided includes Notable Accomplishments, a performance profile with associated analyses, Critical Issues, Key Integration Activities, and a ''quick list'' of Upcoming Key Events. Section B of this report, the Site Summary section, provides Environmental Management performance data specifically organized to the pertinent Critical Success Factors and Success Indicators, and Science and Technology data in the context of the Critical Outcomes. The Site Summary demonstrates the various missions' overall progress against these strategic objectives. The information is presented in both narrative and graphical formats. The remaining sections provide performance data relative to each individual mission area (e.g., Waste Management, Spent Nuclear Fuels, etc.). The information provided in the Mission Area sections is at a level of greater detail than is presented in either the Executive Summary or

Hanford Site Performance Report - May 1999

International Nuclear Information System (INIS)

EDER, D.M.

2001-01-01

The purpose of the Hanford Site Performance Report is to provide the Department of Energy Richland Operations Office's (DOE-RL's) report of Hanford's performance by: U. S. Department of Energy, Richland Operations Office, Project Hanford Management Contract (PHMC) through Fluor Daniel Hanford, Inc. (FDH) and its subcontractors, Environmental Restoration Contract through Bechtel Hanford, Inc. (BHI), and its subcontractors, and Pacific Northwest National Laboratories (PNNL) for Science and Technology (S and T) Mission and support to the Environmental Management (EM). This report is published monthly with the intent of relating work performance and progress in the context of the Success Indicators and Critical Success Factors as outlined in the Hanford Strategic Plan. On a quarterly basis, the report also addresses performance and progress related to the Science and Technology Mission's Critical Outcomes as derived from the Hanford Strategic Plan. Section A of this report is the Executive Summary, encapsulating high-level data in this report into an overall brief. Summary information provided includes Notable Accomplishments, a performance profile with associated analyses, Critical Issues, Key Integration Activities, and a ''quick list'' of Upcoming Key Events. Section B of this report, the Site Summary section, provides Environmental Management performance data specifically organized to the pertinent Critical Success Factors and Success Indicators, and Science and Technology data in the context of the Critical Outcomes. The Site Summary demonstrates the various missions' overall progress against these strategic objectives. The information is presented in both narrative and graphical formats. The remaining sections provide performance data relative to each individual mission area (e.g., Waste Management, Spent Nuclear Fuels, etc.). The information provided in the Mission Area sections is at a level of greater detail than is presented in either the Executive Summary or

Hanford Site Performance Report - April 1999

International Nuclear Information System (INIS)

EDER, D.M.

2001-01-01

The purpose of the Hanford Site Performance Report is to provide the Department of Energy Richland Operations Office's (DOE-RL's) report of Hanford's performance by: U.S. Department of Energy, Richland Operations Office, Project Hanford Management Contract (PHMC) through Fluor Daniel Hanford, Inc. (FDH) and its subcontractors, Environmental Restoration Contract through Bechtel Hanford, Inc. (BHI), and its subcontractors, and Pacific Northwest National Laboratories (PNNL) for Science and Technology (S and T) Mission and support to the Environmental Management (EM). This report is published monthly with the intent of relating work performance and progress in the context of the Success Indicators and Critical Success Factors as outlined in the Hanford Strategic Plan. On a quarterly basis, the report also addresses performance and progress related to the Science and Technology Mission's Critical Outcomes as derived from the Hanford Strategic Plan. Section A of this report is the Executive Summary, encapsulating high-level data in this report into an overall brief. Summary information provided includes Notable Accomplishments, a performance profile with associated analyses, Critical Issues, Key Integration Activities, and a ''quick list'' of Upcoming Key Events. Section B of this report, the Site Summary section, provides Environmental Management performance data specifically organized to the pertinent Critical Success Factors and Success Indicators, and Science and Technology data in the context of the Critical Outcomes. The Site Summary demonstrates the various missions' overall progress against these strategic objectives. The information is presented in both narrative and graphical formats. The remaining sections provide performance data relative to each individual mission area (e.g., Waste Management, Spent Nuclear Fuels, etc.). The information provided in the Mission Area sections is at a level of greater detail than is presented in either the Executive Summary or

Environmental monitoring at Hanford for 1984

International Nuclear Information System (INIS)

Price, K.R.; Carlile, J.M.V.; Dirkes, R.L.; Jaquish, R.E.; Trevathan, M.S.; Woodruff, R.K.

1985-05-01

Environmental surveillance activities performed by the Pacific Northwest Laboratory for the Department of Energy's Hanford Site for 1984 are discussed in this report. Samples of environmental media were collected in support of the Hanford Environmental Monitoring Program to determine radionuclide concentrations in the Hanford environs. Radiological impacts in terms of radiation dose equivalents as a result of Hanford operations are also discussed. Gross beta radioactivity concentrations in airborne particulates at all sampling locations were lower in 1984 than during 1983 as a result of declining levels of worldwide fallout. Slightly higher levels of 85 Kr and 129 I were noted at several onsite and offsite locations. The sampling location in close proximity to the PUREX plant also detected increased 3 H. Very low levels of radionuclides were detected in samples of Columbia River water during 1984. An extensive groundwater monitoring program was performed for the Hanford Site during 1984. The 3 H and nitrate plumes continued to move slowly toward the Columbia River. All 3 H results were within applicable concentration guides. Samples of deer, rabbits, game birds, waterfowl and fish were collected onsite or in the Columbia River at locations where the potential for radionuclide uptake was most likely, or at the nearest locations where wildlife samples were available. Radioisotope levels were measured. Dose rates from external penetrating radiation measured in the vicinity of residential areas were similar to those observed in the previous years, and no contribution from Hanford activities could be identified. An assessment of the 1984 potential radiological impacts attributable to the Hanford operations indicated that measured and calculated radiation doses to the public continued to be low, and well below applicable regulatory limits. 21 refs., 48 figs., 83 tabs

ATR-Hanford site emergency alerting system - 400 Area (F1-F2) and 600 Area (S6-S10)

International Nuclear Information System (INIS)

Whattam, J.W.

1998-01-01

This document provides the results of the acceptance test procedure performed under document number: HNF-2501, Rev 0. This Acceptance Test Procedure has been prepared to demonstrate the Hanford Site Emergency Alerting System functions as required by Specification WHC-S0454, Rev. 1 and project criteria

Independent technical review of the Hanford Tank Farm Operations

International Nuclear Information System (INIS)

1992-07-01

The Independent Technical Assessment of the Hanford Tank Farm Operations was commissioned by the Assistant Secretary for Environmental Restoration and Waste Management on November 1, 1991. The Independent Technical Assessment team conducted on-site interviews and inspections during the following periods: November 18 to 22,1991; April 13 to 17; and April 27 to May 1, 1992. Westinghouse Hanford Company is the management and operating contractor for the Department of Energy at the Hanford site. The Hanford Tank Farm Operations consists of 177 underground storage tanks containing 61 million gallons of high-level radioactive mixed wastes from the chemical reprocessing of nuclear fuel. The Tank Farm Operations also includes associated transfer lines, ancillary equipment, and instrumentation. The Independent Technical Assessment of the Hanford Tank Farm Operations builds upon the prior assessments of the Hanford Waste Vitrification System and the Hanford Site Tank Waste Disposal Strategy.The objective of this technical assessment was to determine whether an integrated and sound program exists to manage the tank-waste storage and tankfarm operations consistent with the Assistant Secretary for Environmental Restoration and Waste Management's guidance of overall risk minimization. The scope of this review includes the organization, management, operation, planning, facilities, and mitigation of the safety-concerns of the Hanford Tank Waste Remediation System. The assessments presented in the body of this report are based on the detailed observations discussed in the appendices. When the assessments use the term ''Hanford'' as an organizational body it means DOE-RL and Westinghouse Hanford Company as a minimum, and in many instances all of the stake holders for the Hanford site

Nicotinamide dependence of uropathogenic Escherichia coli UTI89 and application of nadB as a neutral insertion site.

Science.gov (United States)

Li, Zhaoli; Bouckaert, Julie; Deboeck, Francine; De Greve, Henri; Hernalsteens, Jean-Pierre

2012-03-01

NAD and NADP are ubiquitous in the metabolism of Escherichia coli K-12. NAD auxotrophy can be rendered by mutation in any of the three genes nadB, nadA and nadC. The nadB and nadA genes were defined as antivirulence loci in Shigella spp., as a mutation (mainly in nadB) disrupting the synthesis of quinolinate is required for virulence. Uropathogenic E. coli (UPEC) isolates from acute cystitis patients, exhibiting nicotinamide auxotrophy, were of serotype O18 : K1 : H7. E. coli UTI89, the model uropathogenic and O18 : K1 : H7 strain, requires nicotinamide or quinolinate for growth. A mutation in the nadB gene, encoding L-aspartate oxidase, was shown to be responsible for the nicotinamide requirement of UTI89. This was further confirmed by complementation of UTI89 with a recombinant plasmid harbouring the nadB gene of E. coli K-12. An Ala28Val point mutant of the recombinant plasmid failed to support the growth of UTI89 in minimal medium. This proves that the Ala28Val mutation in the NadB gene of UTI89 completely impedes de novo synthesis of nicotinamide. In spontaneous prototrophic revertants of UTI89, the nadB gene has a Val28Ala mutation. Both analyses implicate that the nicotinamide auxotrophy of UTI89 is caused by a single Ala28Val mutation in NadB. We showed that the same mutation is also present in other NAD auxotrophic E. coli O18 strains. No significant differences were observed between the virulence of isogenic NAD auxotrophic and prototrophic strains in the murine ascending urinary tract infection model. Considering these data, we applied the nadB locus as a neutral site for DNA insertions in the bacterial chromosome. We successfully restored the parental phenotype of a fimH mutant by inserting fimH, with a synthetic em7 promoter, into the nadB gene. This neutral insertion site is of significance for further research on the pathogenicity of UPEC.

Hanford Site sustainable development initiatives

International Nuclear Information System (INIS)

Sullivan, C.T.

1994-05-01

Since the days of the Manhattan Project of World War II, the economic well being of the Tri-Cities (Pasco, Kennewick, and Richland) of Washington State has been tied to the US Department of Energy missions at the nearby Hanford Site. As missions at the Site changed, so did the economic vitality of the region. The Hanford Site is now poised to complete its final mission, that of environmental restoration. When restoration is completed, the Site may be closed and the effect on the local economy will be devastating if action is not taken now. To that end, economic diversification and transition are being planned. To facilitate the process, the Hanford Site will become a sustainable development demonstration project

Gennadi Meleshko predstavil film "Poljot nad vremenjem"

Index Scriptorium Estoniae

2007-01-01

Teleajakirjanike Gennadi ja Jelena Meleshko dokumentaalfilmi "Lend aja kohal" ("Poljot nad vremenem") esitleti 21. novembril Eesti Rahvusraamatukogus. Tervitusega esines ka riigikogu liigr Peeter Tulviste

Changes in NAD content of liver mitochondria from γ-irradiated chick embryos and chickens

International Nuclear Information System (INIS)

Dryanovskij, P.G.; Todorov, B.N.

1977-01-01

NAD content of liver mitochondria from chick embryos and chickens has been shown to decrease after irradiation with a dose of 1000 rad. The changes are better pronounced in the content of NAD than in that of NADH. The dynamics of changes in NAD and NADH contents are dependent on the embryo's age

Hanford Site Environmental Report for calendar year 1992

International Nuclear Information System (INIS)

Woodruff, R.K.; Hanf, R.W.; Lundgren, R.E.

1993-06-01

This report is prepared annually to summarize environmental data and information, describe environmental management performance, and demonstrate the status of compliance with environmental regulations at the Hanford Site. The following sections: describe the Hanford Site and its mission; summarize the status in 1992 of compliance with environmental regulations; describe the environmental programs at the Hanford Site; discuss public dose estimates from 1992 Hanford activities; present information on effluent monitoring and environmental surveillance, including ground-water protection and monitoring, and discuss activities to ensure quality

Hanford Site Environmental Report for calendar year 1992

Energy Technology Data Exchange (ETDEWEB)

Woodruff, R.K.; Hanf, R.W.; Lundgren, R.E. [eds.

1993-06-01

This report is prepared annually to summarize environmental data and information, describe environmental management performance, and demonstrate the status of compliance with environmental regulations at the Hanford Site. The following sections: describe the Hanford Site and its mission; summarize the status in 1992 of compliance with environmental regulations; describe the environmental programs at the Hanford Site; discuss public dose estimates from 1992 Hanford activities; present information on effluent monitoring and environmental surveillance, including ground-water protection and monitoring, and discuss activities to ensure quality.

Hanford Facility contingency plan

International Nuclear Information System (INIS)

Sutton, L.N.; Miskho, A.G.; Brunke, R.C.

1993-10-01

The Hanford Facility Contingency Plan, together with each TSD unit-specific contingency plan, meets the WAC 173-303 requirements for a contingency plan. This plan includes descriptions of responses to a nonradiological hazardous materials spill or release at Hanford Facility locations not covered by TSD unit-specific contingency plans or building emergency plans. This plan includes descriptions of responses for spills or releases as a result of transportation activities, movement of materials, packaging, and storage of hazardous materials

Hanford Mission Plan risk-based prioritization methodologies

International Nuclear Information System (INIS)

Hesser, W.A.; Madden, M.S.; Pyron, N.M.; Butcher, J.L.

1994-08-01

Sites across the US Department (DOE) complex recognize the critical need for a systematic method for prioritizing among their work scope activities. Here at the Hanford Site, Pacific Northwest Laboratory and Westinghouse Hanford Company (WHC) conducted preliminary research into techniques to meet this need and assist managers in making financial resource allocation decisions. This research is a subtask of the risk management task of the Hanford Mission Plan as described in the WHC Integrated Planning Work Breakdown Structure 1.8.2 Fiscal Year 1994 Work Plan. The research team investigated prioritization techniques used at other DOE sites and compared them with the Priority Planning Grid (PPG), a tool used at Hanford. The authors concluded that the PPG could be used for prioritization of resource allocation, but it needed to be revised to better reflect the Site's priorities and objectives. The revised PPG was tested with three Hanford programs, the PPG was modified, and updated procedures were prepared

Public involvement in environmental surveillance at Hanford

International Nuclear Information System (INIS)

Hanf, R.W. Jr.; Patton, G.W.; Woodruff, R.K.; Poston, T.M.

1994-08-01

Environmental surveillance at the Hanford Site began during the mid-1940s following the construction and start-up of the nation's first plutonium production reactor. Over the past approximately 45 years, surveillance operations on and off the Site have continued, with virtually all sampling being conducted by Hanford Site workers. Recently, the US Department of Energy Richland Operations Office directed that public involvement in Hanford environmental surveillance operations be initiated. Accordingly, three special radiological air monitoring stations were constructed offsite, near hanford's perimeter. Each station is managed and operated by two local school teaches. These three stations are the beginning of a community-operated environmental surveillance program that will ultimately involve the public in most surveillance operations around the Site. The program was designed to stimulate interest in Hanford environmental surveillance operations, and to help the public better understand surveillance results. The program has also been used to enhance educational opportunities at local schools

Hanford Site Risk Assessment Methodology. Revision 3

International Nuclear Information System (INIS)

1995-05-01

This methodology has been developed to prepare human health and ecological evaluations of risk as part of the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) remedial investigations (RI) and the Resource conservation and Recovery Act of 1976 (RCRA) facility investigations (FI) performed at the Hanford Site pursuant to the hanford Federal Facility Agreement and Consent Order (Ecology et al. 1994), referred to as the Tri-Party Agreement. Development of the methodology has been undertaken so that Hanford Site risk assessments are consistent with current regulations and guidance, while providing direction on flexible, ambiguous, or undefined aspects of the guidance. The methodology identifies site-specific risk assessment considerations and integrates them with approaches for evaluating human and ecological risk that can be factored into the risk assessment program supporting the Hanford Site cleanup mission. Consequently, the methodology will enhance the preparation and review of individual risk assessments at the Hanford Site

Hanford Nuclear Energy Center study

Energy Technology Data Exchange (ETDEWEB)

Harty, H.

1976-03-16

Studies of a Nuclear Energy Center (NEC) at Hanford have not revealed any insurmountable technical problems, but problems have been identified that appear to be more difficult to resolve than for dispersed siting. Major technical developments in meteorology, and probably in seismology, are needed before an environmental report or safety analysis report could be prepared for an NEC. It would be helpful in further NEC studies if licensing requirements (and related criteria) were defined for them. An NEC will likely cause a step change in the amount of planning and involvement of regional groups in the energy picture compared to dispersed siting. The tools that must be developed for analysis of NECs will probably be used for evaluating dispersed siting in greater detail. NECs will probably bring about the use of dry or wet/dry cooling before it is required in equivalent amount for dispersed plants.

Hanford Nuclear Energy Center study

International Nuclear Information System (INIS)

Harty, H.

1976-01-01

Studies of a Nuclear Energy Center (NEC) at Hanford have not revealed any insurmountable technical problems, but problems have been identified that appear to be more difficult to resolve than for dispersed siting. Major technical developments in meteorology, and probably in seismology, are needed before an environmental report or safety analysis report could be prepared for an NEC. It would be helpful in further NEC studies if licensing requirements (and related criteria) were defined for them. An NEC will likely cause a step change in the amount of planning and involvement of regional groups in the energy picture compared to dispersed siting. The tools that must be developed for analysis of NECs will probably be used for evaluating dispersed siting in greater detail. NECs will probably bring about the use of dry or wet/dry cooling before it is required in equivalent amount for dispersed plants

Regulation of hydrogen production by Enterobacter aerogenes by external NADH and NAD{sup +}

Energy Technology Data Exchange (ETDEWEB)

Zhang, Chong; Ma, Kun; Xing, Xin-Hui [Department of Chemical Engineering, Tsinghua University, Beijing 100084 (China)

2009-02-15

Experiments involving the addition of external nicotinamide adenine dinucleotide, reduced form (NADH) or nicotinamide adenine dinucleotide (NAD{sup +}) have been designed to examine how the hydrogen in Enterobacter aerogenes is liberated by NADH or NAD{sup +}. The addition of external NADH or NAD{sup +} was found to regulate hydrogen production by E. aerogenes in resting cells, batch cultures, and chemostat cultures. Particularly in chemostat cultivation, with the external addition of NADH, hydrogen production via the NADH pathway was decreased, while that via the formate pathway was increased; in the end, the overall hydrogen p was decreased. The addition of NAD{sup +}, on the other hand, gave the opposite results. The membrane-bound hydrogenase was found to play a central role in regulating hydrogen production. The occurrence of NADH oxidation (NAD{sup +} reduction) on the cell membrane resulted in an electron flow across the membrane; this changed the oxidation state and metabolic pattern of the cells, which eventually affected the hydrogen evolution. (author)

Intracellular Redox State Revealed by In Vivo 31P MRS Measurement of NAD+ and NADH Contents in Brains

Science.gov (United States)

Lu, Ming; Zhu, Xiao-Hong; Zhang, Yi; Chen, Wei

2015-01-01

Purpose Nicotinamide adenine dinucleotide (NAD), in oxidized (NAD+) or reduced (NADH) form, plays key roles in cellular metabolism. Intracellular NAD+/NADH ratio represents the cellular redox state; however, it is difficult to measure in vivo. We report here a novel in vivo 31P MRS method for noninvasive measurement of intracellular NAD concentrations and NAD+/NADH ratio in the brain. Methods It uses a theoretical model to describe the NAD spectral patterns at a given field for quantification. Standard NAD solutions and independent cat brain measurements at 9.4 T and 16.4 T were used to evaluate this method. We also measured T1 values of brain NAD. Results Model simulation and studies of solutions and brains indicate that the proposed method can quantify submillimolar NAD concentrations with reasonable accuracy if adequate 31P MRS signal-to-noise ratio and linewidth were obtained. The NAD concentrations and NAD+/NADH ratio of cat brains measured at 16.4 T and 9.4 T were consistent despite the significantly different T1 values and NAD spectra patterns at two fields. Conclusion This newly established 31P MRS method makes it possible for the first time to noninvasively study the intracellular redox state and its roles in brain functions and diseases, and it can potentially be applied to other organs. PMID:23843330

Hanford Site cleanup and transition: Risk data needs for decision making (Hanford risk data gap analysis decision guide)

International Nuclear Information System (INIS)

Gajewski, S.; Glantz, C.; Harper, B.; Bilyard, G.; Miller, P.

1995-10-01

Given the broad array of environmental problems, technical alternatives, and outcomes desired by different stakeholders at Hanford, DOE will have to make difficult resource allocations over the next few decades. Although some of these allocations will be driven purely by legal requirements, almost all of the major objectives of the cleanup and economic transition missions involve choices among alternative pathways. This study examined the following questions: what risk information is needed to make good decisions at Hanford; how do those data needs compare to the set(s) of risk data that will be generated by regulatory compliance activities and various non-compliance studies that are also concerned with risk? This analysis examined the Hanford Site missions, the Hanford Strategic Plan, known stakeholder values, and the most important decisions that have to be made at Hanford to determine a minimum domain of risk information required to make good decisions that will withstand legal, political, and technical scrutiny. The primary risk categories include (1) public health, (2) occupational health and safety, (3) ecological integrity, (4) cultural-religious welfare, and (5) socio-economic welfare

Second Quarter Hanford Seismic Report for Fiscal Year 2008

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2008-06-26

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The Hanford Seismic Assessment Team locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. For the Hanford Seismic Network, seven local earthquakes were recorded during the second quarter of fiscal year 2008. The largest event recorded by the network during the second quarter (February 3, 2008 - magnitude 2.3 Mc) was located northeast of Richland in Franklin County at a depth of 22.5 km. With regard to the depth distribution, two earthquakes occurred at shallow depths (less than 4 km, most likely in the Columbia River basalts), three earthquakes at intermediate depths (between 4 and 9 km, most likely in the pre-basalt sediments), and two earthquakes were located at depths greater than 9 km, within the crystalline basement. Geographically, five earthquakes occurred in swarm areas and two earthquakes were classified as random events.

NAD+-Carrying Mesoporous Silica Nanoparticles Can Prevent Oxidative Stress-Induced Energy Failures of Both Rodent Astrocytes and PC12 Cells

Science.gov (United States)

Chen, Heyu; Wang, Yao; Zhang, Jixi; Ma, Yingxin; Wang, Caixia; Zhou, Ying; Gu, Hongchen; Ying, Weihai

2013-01-01

Aim To test the hypothesis that NAD+-carrying mesoporous silica nanoparticles (M-MSNs@NAD+) can effectively deliver NAD+ into cells to produce cytoprotective effects. Methods & Materials NAD+ was incorporated into M-MSNs. Primary rat astrocyte cultures and PC12 cells were treated with H2O2, followed by post-treatment with M-MSNs@NAD+. After various durations of the post-treatment, intracellular NAD+ levels, intracellular ATP levels and lactate dehydrogenase (LDH) release were determined. Results & Discussion M-MSNs can be effectively loaded with NAD+. The M-MSNs@NAD+ can significantly attenuate H2O2-induced NAD+ and ATP decreases in both astrocyte cultures and PC12 cells. M-MSNs@NAD+ can also partially prevent the H2O2-induced LDH release from both astrocyte cultures and PC12 cells. In contrast, the NAD+ that is spontaneously released from the M-MSNs@NAD+ is insufficient to prevent the H2O2-induced damage. Conclusions Our study has suggested the first approach that can effectively deliver NAD+ into cells, which provides an important basis both for elucidating the roles of intracellular NAD+ in biological functions and for therapeutic applications of NAD+. Our study has also provided the first direct evidence demonstrating a key role of NAD+ depletion in oxidative stress-induced ATP decreases. PMID:24040179

MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption.

Science.gov (United States)

Posavec Marjanović, Melanija; Hurtado-Bagès, Sarah; Lassi, Maximilian; Valero, Vanesa; Malinverni, Roberto; Delage, Hélène; Navarro, Miriam; Corujo, David; Guberovic, Iva; Douet, Julien; Gama-Perez, Pau; Garcia-Roves, Pablo M; Ahel, Ivan; Ladurner, Andreas G; Yanes, Oscar; Bouvet, Philippe; Suelves, Mònica; Teperino, Raffaele; Pospisilik, J Andrew; Buschbeck, Marcus

2017-11-01

Histone variants are structural components of eukaryotic chromatin that can replace replication-coupled histones in the nucleosome. The histone variant macroH2A1.1 contains a macrodomain capable of binding NAD + -derived metabolites. Here we report that macroH2A1.1 is rapidly induced during myogenic differentiation through a switch in alternative splicing, and that myotubes that lack macroH2A1.1 have a defect in mitochondrial respiratory capacity. We found that the metabolite-binding macrodomain was essential for sustained optimal mitochondrial function but dispensable for gene regulation. Through direct binding, macroH2A1.1 inhibits basal poly-ADP ribose polymerase 1 (PARP-1) activity and thus reduces nuclear NAD + consumption. The resultant accumulation of the NAD + precursor NMN allows for maintenance of mitochondrial NAD + pools that are critical for respiration. Our data indicate that macroH2A1.1-containing chromatin regulates mitochondrial respiration by limiting nuclear NAD + consumption and establishing a buffer of NAD + precursors in differentiated cells.

Radionuclide releases to the atmosphere from Hanford Operations, 1944--1972. Hanford Environmental Dose Reconstruction Project

Energy Technology Data Exchange (ETDEWEB)

Heeb, C.M.

1994-05-01

The purpose of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation dose that individuals could have received as a result of radionuclide emissions since 1944 from the Hanford Site. The first step in determining dose is to estimate the amount and timing of radionuclide releases to air and water. This report provides the air release information.

Researchers take up environmental challenge at Hanford

International Nuclear Information System (INIS)

Illman, D.L.

1993-01-01

The Hanford nuclear site, built to produce plutonium for the nation's first atomic weapons, occupies 560 square miles of desert in southeastern Washington State. Only 29 months after ground was broken at the site in March 1943, the Hanford project delivered the plutonium used in the bomb that was dropped on Nagasaki, Japan, at the end of World War II. Secrecy surrounding the nuclear weapons program continued through the Cold War years, concealing the fact that for decades, hazardous and radioactive wastes were discharged to the ground, water, and air at Hanford. Only in 1986 were documents finally declassified--tens of thousands of them--describing the construction, operation, and maintenance of the Hanford facilities, allowing a picture to be pieced together of the environmental cost there of the nuclear weapons buildup. That cost may never be completely tallied. But Westinghouse Hanford, Co., the principal operations contractor on the site, and Pacific Northwest Laboratories (PNL), operated by Battelle Memorial Institute for the Department of Energy (DOE), have now begun working together to develop new technologies that are needed to address the short-term and long-term challenges of environmental restoration at Hanford. The paper discusses the problems and possible solutions that are being investigated

Listed waste history at Hanford facility TSD units

International Nuclear Information System (INIS)

Miskho, A.G.

1996-01-01

This document was prepared to close out an occurrence report that Westinghouse Hanford Company issued on December 29, 1994. Occurrence Report RL-WHC-GENERAL-1994-0020 was issued because knowledge became available that could have impacted start up of a Hanford Site facility. The knowledge pertained to how certain wastes on the Hanford Site were treated, stored, or disposed of. This document consolidates the research performed by Westinghouse Hanford Company regarding listed waste management at onsite laboratories that transfer waste to the Double-Shell Tank System. Liquid and solid (non-liquid) dangerous wastes and mixed wastes at the Hanford Site are generated from various Site operations. These wastes may be sampled and characterized at onsite laboratories to meet waste management requirements. In some cases, the wastes that are generated in the field or in the laboratory from the analysis of samples require further management on the Hanford Site and are aggregated together in centralized tank storage facilities. The process knowledge presented herein documents the basis for designation and management of 242-A Evaporator Process Condensate, a waste stream derived from the treatment of the centralized tank storage facility waste (the Double-Shell Tank System). This document will not be updated as clean up of the Hanford Site progresses

TRACKING CLEAN UP AT HANFORD

International Nuclear Information System (INIS)

CONNELL, C.W.

2005-01-01

The Hanford Federal Facility Agreement and Consent Order, known as the ''Tri-Party Agreement'' (TPA), is a legally binding agreement among the US Department of Energy (DOE), The Washington State Department of Ecology, and the US Environmental Protection Agency (EPA) for cleaning up the Hanford Site. Established in the 1940s to produce material for nuclear weapons as part of the Manhattan Project, Hanford is often referred to as the world's large environmental cleanup project. The Site covers more than 580 square miles in a relatively remote region of southeastern Washington state in the US. The production of nuclear materials at Hanford has left a legacy of tremendous proportions in terms of hazardous and radioactive waste. From a waste-management point of view, the task is enormous: 1700 waste sites; 450 billion gallons of liquid waste; 70 billion gallons of contaminated groundwater; 53 million gallons of tank waste; 9 reactors; 5 million cubic yards of contaminated soil; 22 thousand drums of mixed waste; 2.3 tons of spent nuclear fuel; and 17.8 metric tons of plutonium-bearing material and this is just a partial listing. The agreement requires that DOE provide the results of analytical laboratory and non-laboratory tests/readings to the lead regulatory agency to help guide then in making decisions. The agreement also calls for each signatory to preserve--for at least ten years after the Agreement has ended--all of the records in it, or its contractors, possession related to sampling, analysis, investigations, and monitoring conducted. The Action Plan that supports the TPA requires that Ecology and EPA have access to all data that is relevant to work performed, or to be performed, under the Agreement. Further, the Action Plan specifies two additional requirements: (1) that EPA, Ecology and their respective contractor staffs have access to all the information electronically, and (2) that the databases are accessible to, and used by, all personnel doing TPA

Potential radiation doses from 1994 Hanford Operations

Energy Technology Data Exchange (ETDEWEB)

Soldat, J.K.; Antonio, E.J.

1995-06-01

This section of the 1994 Hanford Site Environmental Report summarizes the potential radiation doses to the public from releases originating at the Hanford Site. Members of the public are potentially exposed to low-levels of radiation from these effluents through a variety of pathways. The potential radiation doses to the public were calculated for the hypothetical MEI and for the general public residing within 80 km (50 mi) of the Hanford Site.

Potential radiation doses from 1994 Hanford Operations

International Nuclear Information System (INIS)

Soldat, J.K.; Antonio, E.J.

1995-01-01

This section of the 1994 Hanford Site Environmental Report summarizes the potential radiation doses to the public from releases originating at the Hanford Site. Members of the public are potentially exposed to low-levels of radiation from these effluents through a variety of pathways. The potential radiation doses to the public were calculated for the hypothetical MEI and for the general public residing within 80 km (50 mi) of the Hanford Site

Vascular Plants of the Hanford Site

Energy Technology Data Exchange (ETDEWEB)

Sackschewsky, Michael R.; Downs, Janelle L.

2001-09-28

This report provides an updated listing of the vascular plants present on and near the U.S. Department of Energy Hanford Site. This document is an update of a listing of plants prepared by Sackschewdky et al. in 1992. Since that time there has been a significant increase in the botanical knowledge of the Hanford Site. The present listing is based on an examination of herbarium collections held at PNNL, at WSU-Tri Cities, WSU-Pullman, Bringham Young University, and The University of Washington, and on examination of ecological literature derived from the Hanford and Benton county areas over the last 100 years. Based on the most recent analysis, there are approximately 725 different plant species that have been documented on or around the Hanford Site. This represents an approximate 20% increase in the number of species reported within Sackschewsky et al. (1992). This listing directly supports DOE and contractor efforts to assess the potential impacts of Hanford Site operations on the biological environment, including impacts to rare habitats and to species listed as endangered or\\ threatened. This document includes a listing of plants currently listed as endangered, threatened, or otherwise of concern to the Washington Natural Heritage Program or the U.S. Fish and Wildlife Service, as well as those that are currently listed as noxious weeds by the State of Washington. Also provided is an overview of how plants on the Hanford Site can be used by people. This information may be useful in developing risk assessment models, and as supporting information for clean-up level and remediation decisions.

NAD+ metabolite levels as a function of vitamins and calorie restriction: evidence for different mechanisms of longevity

Directory of Open Access Journals (Sweden)

Song Peng

2010-02-01

Full Text Available Abstract Background NAD+ is a coenzyme for hydride transfer enzymes and a substrate for sirtuins and other NAD+-dependent ADPribose transfer enzymes. In wild-type Saccharomyces cerevisiae, calorie restriction accomplished by glucose limitation extends replicative lifespan in a manner that depends on Sir2 and the NAD+ salvage enzymes, nicotinic acid phosphoribosyl transferase and nicotinamidase. Though alterations in the NAD+ to nicotinamide ratio and the NAD+ to NADH ratio are anticipated by models to account for the effects of calorie restriction, the nature of a putative change in NAD+ metabolism requires analytical definition and quantification of the key metabolites. Results Hydrophilic interaction chromatography followed by tandem electrospray mass spectrometry were used to identify the 12 compounds that constitute the core NAD+ metabolome and 6 related nucleosides and nucleotides. Whereas yeast extract and nicotinic acid increase net NAD+ synthesis in a manner that can account for extended lifespan, glucose restriction does not alter NAD+ or nicotinamide levels in ways that would increase Sir2 activity. Conclusions The results constrain the possible mechanisms by which calorie restriction may regulate Sir2 and suggest that provision of vitamins and calorie restriction extend lifespan by different mechanisms.

Hydrogeologic model for the old Hanford townsite

International Nuclear Information System (INIS)

MacDonald, Q.; Csun, C.

1994-01-01

The Hanford Site in southeastern Washington state produced the country's first plutonium during WW II, and production continued through the end of the cold war. This plutonium production generated significant volumes of chemical and radioactive wastes, some of which were discharged directly to the local sediments as wastewater. Artifical recharge is still the dominating influence on the uppermost and unconfined aquifer over much of the Hanford site. Groundwater from a portion of this aquifer, which is in excess of drinking water standards for tritium, discharges to the Columbia River in the vicinity of the old Hanford townsite. The Hanford site lies within the Pasco basin, which is a structural basin in the Columbia Plateau. Columbia River basalt is overlain by the fluvial and lacustrian Ringold formation. The Ringold is unconformably overlain by the informal Hanford formation. Relatively impermeable basalt outcrops and subcrops along a northwest-southeast-trending anticline across the study area. Hanford sediments include both fluvial and glacial flood deposits lying on an irregular surface of basalt and sedimentary rocks. The coarser flood deposits have very high hydraulic conductivity and probably are the most important conduit for contaminant transport within the aquifer. A finite element model (CFEST-SC) is being used to study the effect of changing river stage on baseflow to the Columbia River near the old Hanford townsite. A steady-state version of the model produces calculated head within 1 m of observed values. Transient flow and solute transport results are expected to help further define the relationship between the contaminated aquifer and the Columbia River

Hanford science and technology needs statements document

Energy Technology Data Exchange (ETDEWEB)

Piper, L.L.

1997-12-31

This document is a compilation of the Hanford science and technology needs statements for FY 1998. The needs were developed by the Hanford Site Technology Coordination Group (STCG) with full participation and endorsement of site user organizations, stakeholders, and regulators. The purpose of this document is to: (a) provide a comprehensive listing of Hanford science and technology needs, and (b) identify partnering and commercialization opportunities with industry, other federal and state agencies, and the academic community. The Hanford STCG reviews and updates the needs annually. Once completed, the needs are communicated to DOE for use in the development and prioritization of their science and technology programs, including the Focus Areas, Cross-Cutting Programs, and the Environmental Management Science Program. The needs are also transmitted to DOE through the Accelerating Cleanup: 2006 Plan. The public may access the need statements on the Internet on: the Hanford Home Page (www.hanford.gov), the Pacific Rim Enterprise Center`s web site (www2.pacific-rim.org/pacific rim), or the STCG web site at DOE headquarters (em-52.em.doegov/ifd/stcg/stcg.htm). This page includes links to science and technology needs for many DOE sites. Private industry is encouraged to review the need statements and contact the Hanford STCG if they can provide technologies that meet these needs. On-site points of contact are included at the ends of each need statement. The Pacific Rim Enterprise Center (206-224-9934) can also provide assistance to businesses interested in marketing technologies to the DOE.

Tributyltin induces mitochondrial fission through NAD-IDH dependent mitofusin degradation in human embryonic carcinoma cells.

Science.gov (United States)

Yamada, Shigeru; Kotake, Yaichiro; Nakano, Mizuho; Sekino, Yuko; Kanda, Yasunari

2015-08-01

Organotin compounds, such as tributyltin (TBT), are well-known endocrine disruptors. TBT acts at the nanomolar level through genomic pathways via the peroxisome proliferator activated receptor (PPAR)/retinoid X receptor (RXR). We recently reported that TBT inhibits cell growth and the ATP content in the human embryonic carcinoma cell line NT2/D1 via a non-genomic pathway involving NAD(+)-dependent isocitrate dehydrogenase (NAD-IDH), which metabolizes isocitrate to α-ketoglutarate. However, the molecular mechanisms by which NAD-IDH mediates TBT toxicity remain unclear. In the present study, we evaluated the effects of TBT on mitochondrial NAD-IDH and energy production. Staining with MitoTracker revealed that nanomolar TBT levels induced mitochondrial fragmentation. TBT also degraded the mitochondrial fusion proteins, mitofusins 1 and 2. Interestingly, apigenin, an inhibitor of NAD-IDH, mimicked the effects of TBT. Incubation with an α-ketoglutarate analogue partially recovered TBT-induced mitochondrial dysfunction, supporting the involvement of NAD-IDH. Our data suggest that nanomolar TBT levels impair mitochondrial quality control via NAD-IDH in NT2/D1 cells. Thus, mitochondrial function in embryonic cells could be used to assess cytotoxicity associated with metal exposure.

Natural phenomena analyses, Hanford Site, Washington

International Nuclear Information System (INIS)

Tallman, A.M.

1989-01-01

Probabilistic seismic hazard studies completed for the Washington Public Power Supply System's Nuclear Plant 2 and for the US Department of Energy's N Reactor sites, both on the Hanford Site, suggested that the Lawrence Livermore National Laboratory seismic exposure estimates were lower than appropriate, especially for sites near potential seismic sources. A probabilistic seismic hazard assessment was completed for those areas that contain process and/or waste management facilities. the lower bound magnitude of 5.0 is used in the hazard analysis and the characteristics of small-magnitude earthquakes relatively common to the Hanford Site are addressed. The recommended ground motion for high-hazard facilities is somewhat higher than the Lawrence Livermore National Laboratory model and the ground motion from small-magnitude earthquakes is addressed separately from the moderate- to large-magnitude earthquake ground motion. The severe wind and tornado hazards determined for the Hanford Siste are in agreement with work completed independently using 43 years of site data. The low-probability, high-hazard, design-basis flood at the Hanford Site is dominated by dam failure on the Columbia River. Further evaluation of the mechanisms and probabilities of such flooding is in progress. The Hanford Site is downwind from several active Cascade volcanoes. Geologic and historical data are used to estimate the ashfall hazard

Hanford Waste Vitrification Plant Technology Plan

International Nuclear Information System (INIS)

Sexton, R.A.

1988-06-01

The reference Hanford plan for disposal of defense high-level waste is based on waste immobilization in glass by the vitrification process and temporary vitrified waste storage at the Hanford Site until final disposal in a geologic repository. A companion document to the Hanford Waste Management Plan (HWMP) is the Draft, Interim Hanford Waste Management Technology Plan (HWMTP), which provides a description of the technology that must be developed to meet the reference waste management plan. One of the issues in the HWMTP is DST-6, Immobilization (Glass). The HWMTP includes all expense funding needed to complete the Hanford Waste Vitrification Plant (HWVP) project. A preliminary HWVP Technology Plan was prepared in 1985 as a supporting document to the HWMTP to provide a more detailed description of the technology needed to construct and operate a vitrification facility. The plan was updated and issued in 1986, and revised in 1987. This document is an annual update of the plan. The HWVP Technology Plan is limited in scope to technology that requires development or confirmation testing. Other expense-funded activities are not included. The relationship between the HWVP Technology Plan and other waste management issues addressed in the HWMTP is described in section 1.6 of this plan. 6 refs., 4 figs., 34 tabs

Hanford groundwater scenario studies

International Nuclear Information System (INIS)

Arnett, R.C.; Gephart, R.E.; Deju, R.A.; Cole, C.R.; Ahlstrom, S.W.

1977-05-01

This report documents the results of two Hanford groundwater scenario studies. The first study examines the hydrologic impact of increased groundwater recharge resulting from agricultural development in the Cold Creek Valley located west of the Hanford Reservation. The second study involves recovering liquid radioactive waste which has leaked into the groundwater flow system from a hypothetical buried tank containing high-level radioactive waste. The predictive and control capacity of the onsite Hanford modeling technology is used to evaluate both scenarios. The results of the first study indicate that Cold Creek Valley irrigationis unlikely to cause significant changes in the water table underlying the high-level waste areas or in the movement of radionuclides already in the groundwater. The hypothetical tank leak study showed that an active response (in this case waste recovery) can be modeled and is a possible alternative to passive monitoring of radionuclide movement in the unlikely event that high-level waste is introduced into the groundwater

Hanford Waste Vitrification Plant

International Nuclear Information System (INIS)

Larson, D.E.; Allen, C.R.; Kruger, O.L.; Weber, E.T.

1991-10-01

The Hanford Waste Vitrification Plant (HWVP) is being designed to immobilize pretreated Hanford high-level waste and transuranic waste in borosilicate glass contained in stainless steel canisters. Testing is being conducted in the HWVP Technology Development Project to ensure that adapted technologies are applicable to the candidate Hanford wastes and to generate information for waste form qualification. Empirical modeling is being conducted to define a glass composition range consistent with process and waste form qualification requirements. Laboratory studies are conducted to determine process stream properties, characterize the redox chemistry of the melter feed as a basis for controlling melt foaming and evaluate zeolite sorption materials for process waste treatment. Pilot-scale tests have been performed with simulated melter feed to access filtration for solids removal from process wastes, evaluate vitrification process performance and assess offgas equipment performance. Process equipment construction materials are being selected based on literature review, corrosion testing, and performance in pilot-scale testing. 3 figs., 6 tabs

First Quarter Hanford Seismic Report for Fiscal Year 2011

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Clayton, Ray E.; Devary, Joseph L.

2011-03-31

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The HSAP is responsible for locating and identifying sources of seismic activity and monitoring changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the HSAP works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. The Hanford Seismic Network recorded 16 local earthquakes during the first quarter of FY 2011. Six earthquakes were located at shallow depths (less than 4 km), seven earthquakes at intermediate depths (between 4 and 9 km), most likely in the pre-basalt sediments, and three earthquakes were located at depths greater than 9 km, within the basement. Geographically, thirteen earthquakes were located in known swarm areas and three earthquakes were classified as random events. The highest magnitude event (1.8 Mc) was recorded on October 19, 2010 at depth 17.5 km with epicenter located near the Yakima River between the Rattlesnake Mountain and Horse Heaven Hills swarm areas.

Mitochondrial NAD(PH in vivo: identifying natural indicators of oxidative phosphorylation in the 31P magnetic resonance spectrum.

Directory of Open Access Journals (Sweden)

Kevin eConley

2016-03-01

Full Text Available Natural indicators provide intrinsic probes of metabolism, biogenesis and oxidative protection. Nicotinamide adenine dinucleotide metabolites (NAD(P are one class of indicators that have roles as co-factors in oxidative phosphorylation, glycolysis and anti-oxidant protection, as well as signaling in the mitochondrial biogenesis pathway. These many roles are made possible by the distinct redox states (NAD(P+ and NAD(PH, which are compartmentalized between cell and mitochondria. Here we provide evidence for detection of NAD(P+ and NAD(PH in separate mitochondrial and cell pools in vivo in human tissue by phosphorus magnetic resonance spectroscopy (31P MRS. These NAD(P pools are identified by chemical standards (NAD+, NADP+ and NADH and by physiological tests. A unique resonance reflecting mitochondrial NAD(PH is revealed by the changes elicited by elevation of mitochondrial oxidation. The decline of NAD(PH with oxidation is matched by a stoichiometric rise in the NAD(P+ peak. This unique resonance also provides a measure of the improvement in mitochondrial oxidation that parallels the greater phosphorylation found after exercise training in these elderly subjects. The implication is that the dynamics of the mitochondrial NAD(PH peak provides an intrinsic probe of the reversal of mitochondrial dysfunction in elderly muscle. Thus non-invasive detection of NAD(P+ and NAD(PH in cell vs. mitochondria yield natural indicators of redox compartmentalization and sensitive intrinsic probes of the improvement of mitochondrial function with an intervention in human tissues in vivo. These natural indicators hold the promise of providing mechanistic insight into metabolism and mitochondrial function in vivo in a range of tissues in health, disease and with treatment.

Hanford internal dosimetry program manual

International Nuclear Information System (INIS)

Carbaugh, E.H.; Sula, M.J.; Bihl, D.E.; Aldridge, T.L.

1989-10-01

This document describes the Hanford Internal Dosimetry program. Program Services include administrating the bioassay monitoring program, evaluating and documenting assessments of internal exposure and dose, ensuring that analytical laboratories conform to requirements, selecting and applying appropriate models and procedures for evaluating internal radionuclide deposition and the resulting dose, and technically guiding and supporting Hanford contractors in matters regarding internal dosimetry. 13 refs., 16 figs., 42 tabs

Hanford Site baseline risk assessment methodology. Revision 2

Energy Technology Data Exchange (ETDEWEB)

1993-03-01

This methodology has been developed to prepare human health and environmental evaluations of risk as part of the Comprehensive Environmental Response, Compensation, and Liability Act remedial investigations (RIs) and the Resource Conservation and Recovery Act facility investigations (FIs) performed at the Hanford Site pursuant to the Hanford Federal Facility Agreement and Consent Order referred to as the Tri-Party Agreement. Development of the methodology has been undertaken so that Hanford Site risk assessments are consistent with current regulations and guidance, while providing direction on flexible, ambiguous, or undefined aspects of the guidance. The methodology identifies Site-specific risk assessment considerations and integrates them with approaches for evaluating human and environmental risk that can be factored into the risk assessment program supporting the Hanford Site cleanup mission. Consequently, the methodology will enhance the preparation and review of individual risk assessments at the Hanford Site.

ATP-dependent and NAD-dependent modification of glutamine synthetase from Rhodospirillum rubrum in vitro

International Nuclear Information System (INIS)

Woehle, D.L.; Lueddecke, B.A.; Ludden, P.W.

1990-01-01

Glutamine synthetase from the photosynthetic bacterium Rhodospirillum rubrum is the target of both ATP- and NAD-dependent modification. Incubation of R. rubrum cell supernatant with [α- 32 P]NAD results in the labeling of glutamine synthetase and two other unidentified proteins. Dinitrogenase reductase ADP-ribosyltransferase does not appear to be responsible for the modification of glutamine synthetase or the unidentified proteins. The [α- 32 P]ATP- and [α- 32 P] NAD-dependent modifications of R. rubrum glutamine synthetase appear to be exclusive and the two forms of modified glutamine synthetase are separable on two-dimensional gels. Loss of enzymatic activity by glutamine synthetase did not correlate with [α- 32 P]NAD labeling. This is in contrast to inactivation by nonphysiological ADP-ribosylation of other glutamine synthetases by an NAD:arginine ADP-ribosyltransferase from turkey erythrocytes. A 32 P-labeled protein spot comigrates with the NAD-treated glutamine synthetase spot when glutamine synthetase purified from H 3 32 PO 4 -grown cells is analyzed on two-dimensional gels. The adenylylation site of R. rubrum glutamine synthetase has been determined to be Leu-(Asp)-Tyr-Leu-Pro-Pro-Glu-Glu-Leu-Met; the tyrosine residue is the site of modification

Resource book: Decommissioning of contaminated facilities at Hanford

International Nuclear Information System (INIS)

1991-09-01

In 1942 Hanford was commissioned as a site for the production of weapons-grade plutonium. The years since have seen the construction and operation of several generations of plutonium-producing reactors, plants for the chemical processing of irradiated fuel elements, plutonium and uranium processing and fabrication plants, and other facilities. There has also been a diversification of the Hanford site with the building of new laboratories, a fission product encapsulation plant, improved high-level waste management facilities, the Fast Flux test facility, commercial power reactors and commercial solid waste disposal facilities. Obsolescence and changing requirements will result in the deactivation or retirement of buildings, waste storage tanks, waste burial grounds and liquid waste disposal sites which have become contaminated with varying levels of radionuclides. This manual was established as a written repository of information pertinent to decommissioning planning and operations at Hanford. The Resource Book contains, in several volumes, descriptive information of the Hanford Site and general discussions of several classes of contaminated facilities found at Hanford. Supplementing these discussions are appendices containing data sheets on individual contaminated facilities and sites at Hanford. Twelve appendices are provided, corresponding to the twelve classes into which the contaminated facilities at Hanford have been organized. Within each appendix are individual data sheets containing administrative, geographical, physical, radiological, functional and decommissioning information on each facility within the class. 68 refs., 54 figs., 18 tabs

Resource book: Decommissioning of contaminated facilities at Hanford

International Nuclear Information System (INIS)

1991-09-01

In 1942 Hanford was commissioned as a site for the production of weapons-grade plutonium. The years since have seen the construction and operation of several generations of plutonium-producing reactors, plants for the chemical processing of irradiated fuel elements, plutonium and uranium processing and fabrication plants, and other facilities. There has also been a diversification of the Hanford site with the building of new laboratories, a fission product encapsulation plant, improved high-level waste management facilities, the Fast Flux test facility, commercial power reactors and commercial solid waste disposal facilities. Obsolescence and changing requirements will result in the deactivation or retirement of buildings, waste storage tanks, waste burial grounds and liquid waste disposal sites which have become contaminated with varying levels of radionuclides. This manual was established as a written repository of information pertinent to decommissioning planning and operations at Hanford. The Resource Book contains, in several volumes, descriptive information of the Hanford Site and general discussions of several classes of contaminated facilities found at Hanford. Supplementing these discussions are appendices containing data sheets on individual contaminated facilities and sites at Hanford. Twelve appendices are provided, corresponding to the twelve classes into which the contaminated facilities at Hanford have been organized. Within each appendix are individual data sheets containing administrative, geographical, physical, radiological, functional and decommissioning information on each facility within the class. 49 refs., 44 figs., 14 tabs

The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity

Science.gov (United States)

Wang, Xiaowan; Li, Hailong; Ding, Shinghua

2014-01-01

NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

Pancreatic Beta-Cell Purification by Altering FAD and NAD(PH Metabolism

Directory of Open Access Journals (Sweden)

P. de Vos

2008-07-01

Full Text Available Isolation of primary beta cells from other cells within in the pancreatic islets is of importance for many fields of islet research. However, up to now, no satisfactory method has been developed that gained high numbers of viable beta cells, without considerable alpha-cell contamination. In this study, we investigated whether rat beta cells can be isolated from nonbeta endocrine cells by manipulating the flavin adenine dinucleotide (FAD and nicotinamide-adenine dinucleotide phosphate (NAD(PH autofluorescence. Beta cells were isolated from dispersed islets by flow cytometry, based on their high FAD and NAD(PH fluorescence. To improve beta cell yield and purity, the cellular FAD and NAD(PH contents were altered by preincubation in culture media containing varying amounts of D-glucose and amino acids. Manipulation of the cellular FAD and NAD(PH fluorescence improves beta cell yield and purity after sorting. This method is also a fast and reliable method to measure beta cell functional viability. A conceivable application is assessing beta cell viability before transplantation.

GENII: The Hanford Environmental Radiation Dosimetry Software System: Volume 2, Users' manual: Hanford Environmental Dosimetry Upgrade Project

International Nuclear Information System (INIS)

Napier, B.A.; Peloquin, R.A.; Strenge, D.L.; Ramsdell, J.V.

1988-11-01

The Hanford Environmental Dosimetry Upgrade Project was undertaken to incorporate the internal dosimetry models recommended by the International Commission on Radiological Protection (ICRP) in updated versions of the environmental pathway analysis models used at Hanford. The resulting second generation of Hanford environmental dosimetry computer codes is compiled in the Hanford Environmental Dosimetry System (Generation II, or GENII). The purpose of this coupled system of computer codes is to analyze environmental contamination of, air, water, or soil. This is accomplished by calculating radiation doses to individuals or populations. GENII is described in three volumes of documentation. This second volume is a Users' Manual, providing code structure, users' instructions, required system configurations, and QA-related topics. The first volume describes the theoretical considerations of the system. The third volume is a Code Maintenance Manual for the user who requires knowledge of code detail. It includes logic diagrams, global dictionary, worksheets, example hand calculations, and listings of the code and its associated data libraries. 27 refs., 17 figs., 23 tabs

Third Quarter Hanford Seismic Report for Fiscal Year 2000

Energy Technology Data Exchange (ETDEWEB)

DC Hartshorn; SP Reidel; AC Rohay

2000-09-01

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the U.S. Department of Energy and its con-tractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (E WRN) consist of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The HSN uses 21 sites and the EWRN uses 36 sites; both networks share 16 sites. The networks have 46 combined data channels because Gable Butte and Frenchman Hills East are three-component sites. The reconfiguration of the telemetry and recording systems was completed during the first quarter. All leased telephone lines have been eliminated and radio telemetry is now used exclusively. For the HSN, there were 818 triggers on two parallel detection and recording systems during the third quarter of fiscal year (FY) 2000. Thirteen seismic events were located by the Hanford Seismic Network within the reporting region of 46-47{degree} N latitude and 119-120{degree} W longitude; 7 were earthquakes in the Columbia River Basalt Group, 1 was an earthquake in the pre-basalt sediments, and 5 were earthquakes in the crystalline basement. Three earthquakes occurred in known swarm areas, and 10 earthquakes were random occurrences. No earthquakes triggered the Hanford Strong Motion Accelerometers during the third quarter of FY 2000.

First Quarter Hanford Seismic Report for Fiscal Year 2008

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2008-03-21

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The Hanford Seismic Assessment Team locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 41 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. For the Hanford Seismic Network, forty-four local earthquakes were recorded during the first quarter of fiscal year 2008. A total of thirty-one micro earthquakes were recorded within the Rattlesnake Mountain swarm area at depths in the 5-8 km range, most likely within the pre-basalt sediments. The largest event recorded by the network during the first quarter (November 25, 2007 - magnitude 1.5 Mc) was located within this swarm area at a depth of 4.3 km. With regard to the depth distribution, three earthquakes occurred at shallow depths (less than 4 km, most likely in the Columbia River basalts), thirty-six earthquakes at intermediate depths (between 4 and 9 km, most likely in the pre-basalt sediments), and five earthquakes were located at depths greater than 9 km, within the crystalline basement. Geographically, thirty-eight earthquakes occurred in swarm areas and six earth¬quakes were classified as random events.

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

Energy Technology Data Exchange (ETDEWEB)

Rathbone, Bruce A.

2009-08-28

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at Hanford. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with 10 CFR 835, DOELAP, DOE-RL, ORP, PNSO, and Hanford contractor requirements. The dosimetry system is operated by PNNL’s Hanford External Dosimetry Program (HEDP) which provides dosimetry services to all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee (HPDAC) which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. The first revision to be released through PNNL’s Electronic Records & Information Capture Architecture (ERICA) database was designated Revision 0. Revision numbers that are whole numbers reflect major revisions typically involving changes to all chapters in the document. Revision numbers that include a decimal fraction reflect minor revisions, usually restricted to selected chapters or selected pages in the document.

DOE Order 5480.28 Hanford facilities database

Energy Technology Data Exchange (ETDEWEB)

Hayenga, J.L., Westinghouse Hanford

1996-09-01

This document describes the development of a database of DOE and/or leased Hanford Site Facilities. The completed database will consist of structure/facility parameters essential to the prioritization of these structures for natural phenomena hazard vulnerability in compliance with DOE Order 5480.28, `Natural Phenomena Hazards Mitigation`. The prioritization process will be based upon the structure/facility vulnerability to natural phenomena hazards. The ACCESS based database, `Hanford Facilities Site Database`, is generated from current Hanford Site information and databases.

Waste minimization -- Hanford`s strategy for sustainability

Energy Technology Data Exchange (ETDEWEB)

Merry, D.S.

1998-01-30

The Hanford Site cleanup activity is an immense and challenging undertaking, which includes characterization and decommissioning of 149 single-shell storage tanks, treating waste stored in 28 double-shell tanks, safely disposing of over 2,100 metric tons of spent nuclear fuel stored onsite, removing thousands of structures, and dealing with significant solid waste, groundwater, and land restoration issues. The Pollution Prevention/Waste Minimization (P2/WMin) Program supports the Hanford Site mission to safely clean up and manage legacy waste and to develop and deploy science and technology in many ways. Once such way is through implementing and documenting over 231 waste reduction projects during the past five years, resulting in over $93 million in cost savings/avoidances. These savings/avoidances allowed other high priority cleanup work to be performed. Another way is by exceeding the Secretary of Energy`s waste reduction goals over two years ahead of schedule, thus reducing the amount of waste to be stored, treated and disposed. Six key elements are the foundation for these sustained P2/WMin results.

First Quarter Hanford Seismic Report for Fiscal Year 2009

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2009-03-15

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The HSAP is responsible for locating and identifying sources of seismic activity and monitoring changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the HSAP works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. This includes three recently acquired Transportable Array stations located at Cold Creek, Didier Farms, and Phinney Hill. For the Hanford Seismic Network, ten local earthquakes were recorded during the first quarter of fiscal year 2009. All earthquakes were considered as “minor” with magnitudes (Mc) less than 1.0. Two earthquakes were located at shallow depths (less than 4 km), most likely in the Columbia River basalts; five earthquakes at intermediate depths (between 4 and 9 km), most likely in the sub-basalt sediments); and three earthquakes were located at depths greater than 9 km, within the basement. Geographically, four earthquakes occurred in known swarm areas and six earthquakes were classified as random events.

Hanford Dose Overview Program. Comparison of AIRDOS-EPA and Hanford site dose codes

International Nuclear Information System (INIS)

Aaberg, R.L.; Napier, B.A.

1985-11-01

Radiation dose commitments for persons in the Hanford environs calculated using AIRDOS-EPA were compared with those calculated using a suite of Hanford codes: FOOD, PABLM, DACRIN, and KRONIC. Dose commitments to the population and to the maximally exposed individual (MI) based on annual releases of eight radionuclides from the N-Reactor, were calculated by these codes. Dose commitments from each pathway to the total body, lung, thyroid, and lower large intestine (LLI) are given for the population and MI, respectively. 11 refs., 25 tabs

Hanford Site Raptor Nest Monitoring Report for Calendar Year 2013

Energy Technology Data Exchange (ETDEWEB)

Nugent, John J. [Mission Support Alliance (MSA), Richland, WA (United States); Lindsey, Cole T. [Mission Support Alliance (MSA), Richland, WA (United States); Wilde, Justin W. [Mission Support Alliance (MSA), Richland, WA (United States)

2014-02-13

The U.S. Department of Energy, Richland Operations Office (DOE-RL) conducts ecological monitoring on the Hanford Site to collect and track data needed to ensure compliance with an array of environmental laws, regulations, and policies governing DOE activities. Ecological monitoring data provide baseline information about the plants, animals, and habitat under DOE-RL stewardship at Hanford required for decision-making under the National Environmental Policy Act (NEPA) and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). The Hanford Site Comprehensive Land Use Plan (CLUP, DOE/EIS-0222-F) which is the Environmental Impact Statement for Hanford Site activities, helps ensure that DOE-RL, its contractors, and other entities conducting activities on the Hanford Site are in compliance with NEPA. The Hanford Site supports a large and diverse community of raptorial birds (Fitzner et al. 1981), with 26 species of raptors observed on the Hanford Site.

Kinetic and modelling studies of NAD+ and poly(ethylene glycol)-bound NAD+ in horse liver alcohol dehydrogenase

NARCIS (Netherlands)

Vanhommerig, S.A.M.; Sluyterman, L.A.A.E.; Meijer, E.M.

1996-01-01

Poly(ethylene glycol)-bound nicotinamide adenine dinucleotide (PEG-NAD+) has been successfully employed in the continuous production of L-amino acids from the corresponding alpha-keto acids by stereospecific reductive amination. Like many other dehydrogenases also horse liver alcohol dehydrogenase

Hanford Facility Annual Dangerous Waste Report Calendar Year 2002

International Nuclear Information System (INIS)

FR-EEMAN, D.A.

2003-01-01

Hanford CY 2002 dangerous waste generation and management forms. The Hanford Facility Annual Dangerous Waste Report (ADWR) is prepared to meet the requirements of Washington Administrative Code Sections 173-303-220, Generator Reporting, and 173-303-390, Facility Reporting. In addition, the ADWR is required to meet Hanford Facility RCRA Permit Condition I.E.22, Annual Reporting. The ADWR provides summary information on dangerous waste generation and management activities for the Calendar Year for the Hanford Facility EPA ID number assigned to the Department of Energy for RCRA regulated waste, as well as Washington State only designated waste and radioactive mixed waste. The Solid Waste Information and Tracking System (SWITS) database is utilized to collect and compile the large array of data needed for preparation of this report. Information includes details of waste generated on the Hanford Facility, waste generated offsite and sent to Hanford for management, and other waste management activities conducted at Hanford, including treatment, storage, and disposal. Report details consist of waste descriptions and weights, waste codes and designations, and waste handling codes. In addition, for waste shipped to Hanford for treatment and/or disposal, information on manifest numbers, the waste transporter, the waste receiving facility, and the original waste generators are included. In addition to paper copies, electronic copies of the report are also transmitted to the regulatory agency

Pharmacological Inhibitors of NAD Biosynthesis as Potential An ticancer Agents.

Science.gov (United States)

Lucas, Stephanie; Soave, Claire; Nabil, Ghazal; Ahmed, Zainab Sabry Othman; Chen, Guohua; El-Banna, Hossny Awad; Dou, Q Ping; Wang, Jian

2017-01-01

Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics through inhibition of cancer metabolism. Nicotinamide Adenine Dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer. The main objective of this article is to review the recent patents which develop and implicate the chemical inhibitors of the key NAD+ biosynthetic enzymes for cancer treatment. We first discuss the biological principles of NAD+ metabolism in normal and malignant cells, with a focus on the feasibility of selectively targeting cancer cells by pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT) and indoleamine/tryptophan 2,3-dioxygenases (IDO/TDO), the rate-limiting salvage and de novo NAD+ biosynthetic enzymes, respectively. We then analyze a series of recent patents on development and optimization of chemical scaffolds for inhibiting NAMPT or IDO/TDO enzymes as potential anticancer drugs. Conclusion and Results: We have reviewed 16 relevant patents published since 2015, and summarized the chemical properties, mechanisms of action and proposed applications of the patented compounds. Without a better understanding of the properties of these compounds, their utility for further optimization and clinical use is unknown. For the compounds that have been tested using cell and mouse models of cancer, results look promising and clinical trials are currently ongoing to see if these results translate to improved cancer treatments. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Overview of the Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

Shipler, D.B.; Napier, B.A.; Ikenberry, T.A.

1992-04-01

The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that specific and representative individuals and populations may have received as a result of releases of radioactive materials from historical operations at the Hanford Site. These dose estimates would account for the uncertainties of information regarding facilities operations, environmental monitoring, demography, food consumption and lifestyles, and the variability of natural phenomena. Other objectives of the HEDR Project include: supporting the Hanford Thyroid Disease Study (HTDS), declassifying Hanford-generated information and making it available to the public, performing high-quality, credible science, and conducting the project in an open, public forum. The project is briefly described

The NAD(+) precursor nicotinamide riboside decreases exercise performance in rats.

Science.gov (United States)

Kourtzidis, Ioannis A; Stoupas, Andreas T; Gioris, Ioannis S; Veskoukis, Aristidis S; Margaritelis, Nikos V; Tsantarliotou, Maria; Taitzoglou, Ioannis; Vrabas, Ioannis S; Paschalis, Vassilis; Kyparos, Antonios; Nikolaidis, Michalis G

2016-01-01

Nicotinamide adenine dinucleotide (NAD(+)) and its phosphorylated form (NADP(+)) are key molecules in ubiquitous bioenergetic and cellular signaling pathways, regulating cellular metabolism and homeostasis. Thus, supplementation with NAD(+) and NADP(+) precursors emerged as a promising strategy to gain many and multifaceted health benefits. In this proof-of-concept study, we sought to investigate whether chronic nicotinamide riboside administration (an NAD(+) precursor) affects exercise performance. Eighteen Wistar rats were equally divided in two groups that received either saline vehicle or nicotinamide riboside at a dose of 300 mg/kg body weight/day for 21 days via gavage. At the end of the 21-day administration protocol, both groups performed an incremental swimming performance test. The nicotinamide riboside group showed a tendency towards worse physical performance by 35 % compared to the control group at the final 10 % load (94 ± 53 s for the nicotinamide riboside group and 145 ± 59 s for the control group; P = 0.071). Our results do not confirm the previously reported ergogenic effect of nicotinamide riboside. The potentially negative effect of nicotinamide riboside administration on physical performance may be attributed to the pleiotropic metabolic and redox properties of NAD(+) and NADP(+).

NAD+ metabolism and the control of energy homeostasis - a balancing act between mitochondria and the nucleus

Science.gov (United States)

Cantó, Carles; Menzies, Keir; Auwerx, Johan

2015-01-01

NAD+ has emerged as a vital cofactor that can rewire metabolism, activate sirtuins and maintain mitochondrial fitness through mechanisms such as the mitochondrial unfolded protein response. This improved understanding of NAD+ metabolism revived interest in NAD+ boosting strategies to manage a wide spectrum of diseases, ranging from diabetes to cancer. In this review, we summarize how NAD+ metabolism links energy status with adaptive cellular and organismal responses and how this knowledge can be therapeutically exploited. PMID:26118927

NAD-dependent isocitrate dehydrogenase as a novel target of tributyltin in human embryonic carcinoma cells

Science.gov (United States)

Yamada, Shigeru; Kotake, Yaichiro; Demizu, Yosuke; Kurihara, Masaaki; Sekino, Yuko; Kanda, Yasunari

2014-08-01

Tributyltin (TBT) is known to cause developmental defects as endocrine disruptive chemicals (EDCs). At nanomoler concentrations, TBT actions were mediated by genomic pathways via PPAR/RXR. However, non-genomic target of TBT has not been elucidated. To investigate non-genomic TBT targets, we performed comprehensive metabolomic analyses using human embryonic carcinoma NT2/D1 cells. We found that 100 nM TBT reduced the amounts of α-ketoglutarate, succinate and malate. We further found that TBT decreased the activity of NAD-dependent isocitrate dehydrogenase (NAD-IDH), which catalyzes the conversion of isocitrate to α-ketoglutarate in the TCA cycle. In addition, TBT inhibited cell growth and enhanced neuronal differentiation through NAD-IDH inhibition. Furthermore, studies using bacterially expressed human NAD-IDH and in silico simulations suggest that TBT inhibits NAD-IDH due to a possible interaction. These results suggest that NAD-IDH is a novel non-genomic target of TBT at nanomolar levels. Thus, a metabolomic approach may provide new insights into the mechanism of EDC action.

Hanford Site radioactive mixed waste thermal treatment initiative

International Nuclear Information System (INIS)

Place, B.G.; Riddelle, J.G.

1993-03-01

This paper is a progress report of current Westinghouse Hanford Company engineering activities related to the implementation of a program for the thermal treatment of the Hanford Site radioactive mixed waste. Topics discussed include a site-specific engineering study, the review of private sector capability in thermal treatment, and thermal treatment of some of the Hanford Site radioactive mixed waste at other US Department of Energy sites

Hanford general employee training - A million dollar cost beneficial program

International Nuclear Information System (INIS)

Gardner, P.R.

1991-02-01

In January 1990, Westinghouse Hanford Company implemented an interactive videodisc training program entitled Hanford General Employee Training. Covering all Institute of Nuclear Power Operations general employee training objectives, training mandated by US Department of Energy orders, and training prescribed by internal Westinghouse Hanford Company policies, Hanford General Employee Training presents and manages engaging training programs individually tailored to each of the 9,000 employees. Development costs for a sophisticated program such as Hanford General Employee Training were high compared to similar costs for developing ''equivalent'' traditional training. Hardware ($500,000) and labor costs ($400,000) totaled $900,000. Annual maintenance costs, equipment plus labor, are totalling about $200,000. On the benefit side, by consolidating some 17 previous Westinghouse Hanford Company courses and more effectively managing the instructional process, Hanford General Employee Training reduced the average student training time from over 11 hours to just under 4 hours. For 9,000 employees, the computed net annual savings exceeds $1.3 million. 2 refs

Hanford Site Wide Transportation Safety Document [SEC 1 Thru 3

Energy Technology Data Exchange (ETDEWEB)

MCCALL, D L

2002-06-01

This safety evaluation report (SER) documents the basis for the US Department of Energy (DOE), Richland Operations Office (RL) to approve the Hanford Sitewide Transportation Safety Document (TSD) for onsite Transportation and Packaging (T&P) at Hanford. Hanford contractors, on behalf of DOE-RL, prepared and submitted the Hanford Sitewide Transportation Safety Document, DOE/RL-2001-0036, Revision 0, (DOE/RL 2001), dated October 4, 2001, which is referred to throughout this report as the TSD. In the context of the TSD, Hanford onsite shipments are the activities of moving hazardous materials, substances, and wastes between DOE facilities and over roadways where public access is controlled or restricted and includes intra-area and inter-area movements. The TSD sets forth requirements and standards for onsite shipment of radioactive and hazardous materials and wastes within the confines of the Hanford Site on roadways where public access is restricted by signs, barricades, fences, or other means including road closures and moving convoys controlled by Hanford Site security forces.

TANK FARM RETRIEVAL LESSONS LEARNED AT THE HANFORD SITE

International Nuclear Information System (INIS)

DODD RA

2008-01-01

exception to the waste retrieval criteria for a specific tank. Tank waste retrieval has been conducted at the Hanford Site over the last few decades using a method referred to as Past Practice Hydraulic Sluicing. Past Practice Hydraulic Sluicing employs large volumes of DST supernatant and water to dislodge, dissolve, mobilize, and retrieve tank waste. Concern over the leak integrity of SSTs resulted in the need for tank waste retrieval methods capable of using smaller volumes of liquid in a more controlled manner

POTENŢIALUL MORFOLOGIC AL MICROREGIUNII TĂŞNAD

Directory of Open Access Journals (Sweden)

Viorel GLIGOR

2010-11-01

Full Text Available Morphological potential of the Tăşnad Microregion. This study gave special attention to analyzing the relationship between typology prevail relief (defined as part morphological and morphometric, processes associated modeling (with emphasis on current processes and land use. This has been developed quantitative and qualitative assessments, which revealed various types of surfaces share the defining parameters of Tăşnad Microregion and morphodynamic potential relief. Linking these elements with features biopedological fund, hydro-climatic local conditions and degree of anthropogenic intervention, allowed the identification of dysfunctional situations conditional expression riscogene processes and morphological evaluation of pretability optimal exploitation and use of land.

Hanford Site Waste Management Plan

International Nuclear Information System (INIS)

1988-12-01

The Hanford Site Waste Management Plan (HWMP) was prepared in accordance with the outline and format described in the US Department of Energy Orders. The HWMP presents the actions, schedules, and projected costs associated with the management and disposal of Hanford defense wastes, both radioactive and hazardous. The HWMP addresses the Waste Management Program. It does not include the Environmental Restoration Program, itself divided into the Environmental Restoration Remedial Action Program and the Decontamination and Decommissioning Program. The executive summary provides the basis for the plans, schedules, and costs within the scope of the Waste Management Program at Hanford. It summarizes fiscal year (FY) 1988 including the principal issues and the degree to which planned activities were accomplished. It further provides a forecast of FY 1989 including significant milestones. Section 1 provides general information for the Hanford Site including the organization and administration associated with the Waste Management Program and a description of the Site focusing on waste management operations. Section 2 and Section 3 describe radioactive and mixed waste management operations and hazardous waste management, respectively. Each section includes descriptions of the waste management systems and facilities, the characteristics of the wastes managed, and a discussion of the future direction of operations

The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity

NARCIS (Netherlands)

Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

2012-01-01

As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+)

Hanford Site Anuran Monitoring Report for Calendar Year 2013

Energy Technology Data Exchange (ETDEWEB)

Wilde, Justin W. [Mission Support Alliance LLC, Richland, WA (United States); Johnson, Scott J. [Mission Support Alliance LLC, Richland, WA (United States); Lindsey, Cole T. [Mission Support Alliance LLC, Richland, WA (United States)

2014-02-13

The U.S. Department of Energy, Richland Operations Office (DOE-RL) conducts ecological monitoring on the Hanford Site to collect and track data needed to ensure compliance with an array of environmental laws, regulations, and policies governing DOE activities. Ecological monitoring data provide baseline information about the plants, animals, and habitat under DOE-RL stewardship at Hanford required for decision-making under the National Environmental Policy Act (NEPA) and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). The Hanford Site Comprehensive Land Use Plan (CLUP, DOE/EIS-0222-F) which is the Environmental Impact Statement for Hanford Site activities, helps ensure that DOE-RL, its contractors, and other entities conducting activities on the Hanford Site are in compliance with NEPA.

Organic Tank Safety Project: development of a method to measure the equilibrium water content of Hanford organic tank wastes and demonstration of method on actual waste

Energy Technology Data Exchange (ETDEWEB)

Scheele, R.D.; Bredt, P.R.; Sell, R.L.

1996-09-01

Some of Hanford`s underground waste storage tanks contain Organic- bearing high level wastes that are high priority safety issues because of potentially hazardous chemical reactions of organics with inorganic oxidants in these wastes such as nitrates and nitrites. To ensure continued safe storage of these wastes, Westinghouse Hanford Company has placed affected tanks on the Organic Watch List and manages them under special rules. Because water content has been identified as the most efficient agent for preventing a propagating reaction and is an integral part of the criteria developed to ensure continued safe storage of Hanford`s organic-bearing radioactive tank wastes, as part of the Organic Tank Safety Program the Pacific Northwest National Laboratory developed and demonstrated a simple and easily implemented procedure to determine the equilibrium water content of these potentially reactive wastes exposed to the range of water vapor pressures that might be experienced during the wastes` future storage. This work focused on the equilibrium water content and did not investigate the various factors such as @ ventilation, tank surface area, and waste porosity that control the rate that the waste would come into equilibrium, with either the average Hanford water partial pressure 5.5 torr or other possible water partial pressures.

First Quarter Hanford Seismic Report for Fiscal Year 2001

Energy Technology Data Exchange (ETDEWEB)

Hartshorn, Donald C.; Reidel, Stephen P.; Rohay, Alan C.; Valenta, Michelle M.

2001-02-27

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the U.S. Department of Energy and its contractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (EWRN) consist of 41 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. For the HSN, there were 477 triggers during the first quarter of fiscal year (FY) 2001 on the data acquisition system. Of these triggers, 176 were earthquakes. Forty-five earthquakes were located in the HSN area; 1 earthquake occurred in the Columbia River Basalt Group, 43 were earthquakes in the pre-basalt sediments, and 1 was earthquakes in the crystalline basement. Geographically, 44 earthquakes occurred in swarm areas, 1 earthquake was on a major structure, and no earthquakes were classified as random occurrences. The Horse Heaven Hills earthquake swarm area recorded all but one event during the first quarter of FY 2001. The peak of the activity occurred over December 12th, 13th, and 14th when 35 events occurred. No earthquakes triggered the Hanford Strong Motion Accelerometers during the first quarter of FY 2001.

Third Quarter Hanford Seismic Report for Fiscal Year 2008

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2008-09-01

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The Hanford Seismic Assessment Team locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. For the Hanford Seismic Network, fourteen local earthquakes were recorded during the third quarter of fiscal year 2008. The largest event recorded by the network during the third quarter (May 18, 2008 - magnitude 3.7 Mc) was located approximately 17 km east of Prosser at a depth of 20.5 km. With regard to the depth distribution, five earthquakes occurred at shallow depths (less than 4 km, most likely in the Columbia River basalts), six earthquakes at intermediate depths (between 4 and 9 km, most likely in the pre-basalt sediments), and three earthquakes were located at depths greater than 9 km, within the crystalline basement. Geographically, eight earthquakes occurred in swarm areas and six earthquakes were classified as random events. The largest event recorded by the network during the third quarter occurred on May 18 (magnitude 3.7 Mc) and was located approximately 17 km east of Prosser at a depth of 20.5 km. This earthquake was the highest magnitude event recorded in the 46-47 N. latitude / 119-120 W. longitude sector since 1975

Hanford Site performance report - December 1998

International Nuclear Information System (INIS)

EDER, D.M.

2001-01-01

The purpose of the Hanford Site Performance Report is to provide the Department of Energy Richland Operations Office's (DOE-RL's) report of Hanford's performance by: U. S. Department of Energy, Richland Operations Office, Project Hanford Management Contract (PHMC) through Fluor Daniel Hanford, Inc. (FDH) and its subcontractors, Environmental Restoration Contract through Bechtel Hanford, Inc. (BHI), and its subcontractors, and Pacific Northwest National Laboratories (PNNL) for Science and Technology support to the Environmental Management (EM) mission. This report is published monthly with the intent of relating work performance and progress in the context of the Success Indicators and Critical Success Factors as outlined in the Hanford Strategic Plan. Currently, the report focuses on the EM mission, and will be expanded in the future to include non-EM activities. Section A of this report is the Executive Summary, encapsulating high-level data in this report into an overall brief. Summary information provided includes Notable Accomplishments, a tabular performance profile with associated analyses, Critical Issues, Key Integration Activities, a look at Significant Trends, and a ''quick list'' of Upcoming Key Events. Section B of this report, the Site Summary section, provides Environmental Management performance data specifically organized to the pertinent Critical Success Factors and Success Indicators. The Site Summary is a compilation of performance data from all of the Mission Areas and the Projects that comprise these Mission Areas; the information is presented in both narrative and graphical formats. The remaining sections provide performance data relative to each individual mission area (e.g., Waste Management, Spent Nuclear Fuels, etc.). The information provided in the Mission Area sections is at a level of greater detail than is presented in either the Executive Summary or the Site Summary sections. At the end of this report, a glossary of terms is provided

VT NAD83 Orthophoto Boundaries - corner points

Data.gov (United States)

Vermont Center for Geographic Information — (Link to Metadata) RF 5000 NAD83 orthophoto edge lines (4000 x 4000 meter grid cells) were generated automatically from the known corner locations (generated by Gary...

Axial Dispersion during Hanford Saltcake Washing

International Nuclear Information System (INIS)

Josephson, Gary B.; Geeting, John GH; Lessor, Delbert L.; Barton, William B.

2006-01-01

Clean up of Hanford salt cake wastes begins with dissolution retrieval of the sodium rich salts that make up the dominant majority of mass in the tanks. Water moving through the porous salt cake dissolves the soluble components and also displaces the soluble radionuclides (e.g. 137Cs and 99TcO4- ). The separation that occurs from this displacement, known as Selective dissolution, is an important component in Hanford?s pretreatment of low activity wastes for subsequent Supplemental treatment. This paper describes lab scale testing conducted to evaluate Selective dissolution of cesium from non-radioactive Hanford tank 241-S-112 salt cake simulant containing the primary chemicals found the actual tank. An modified axial dispersion model with increasing axial dispersion was developed to predict cesium removal. The model recognizes that water dissolves the salt cake during washing, which causes an increase in the axial dispersion during the wash. This model was subsequently compared with on-line cesium measurements from the retrieval of tank 241-S-112. The model had remarkably good agreement with both the lab scale and full scale data

Software recycling at the Hanford Site

International Nuclear Information System (INIS)

HINKELMAN, K.C.

1999-01-01

The Hanford Site was the first Department of Energy (DOE) complex to recycle excess software rather than dispose of it in the landfill. This plan, which took over a year to complete, was reviewed for potential legal conflicts, which could arise from recycling rather than disposal of software. It was determined that recycling was an approved method of destruction and therefore did not conflict with any of the licensing agreements that Hanford had with the software manufacturers. The Hanford Recycling Program Coordinator combined efforts with Pacific Northwest National Laboratory (PNNL) to recycle all Hanford software through a single contract, which went out for bid in January 1995. It was awarded to GreenDisk, Inc. located in Woodinville Washington and implemented in March 1995. The contract was later re-bid and awarded to EcoDisWGreenDisk in December 1998. The new contract included materials such as; software manuals, diskettes, tyvek wrapping, cardboard and paperboard packaging, compact disks (CDs), videotapes, reel-to-reel tapes, magnetic tapes, audio tapes, and many other types of media

First Quarter Hanford Seismic Report for Fiscal Year 1999

Energy Technology Data Exchange (ETDEWEB)

DC Hartshorn; SP Reidel; AC Rohay

1999-05-26

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the U.S. Department of Energy and its contractors. They also locate and identify sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (EWRN) consists of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The operational rate for the first quarter of FY99 for stations in the HSN was 99.8%. There were 121 triggers during the first quarter of fiscal year 1999. Fourteen triggers were local earthquakes; seven (50%) were in the Columbia River Basalt Group, no earthquakes occurred in the pre-basalt sediments, and seven (50%) were in the crystalline basement. One earthquake (7%) occurred near or along the Horn Rapids anticline, seven earthquakes (50%) occurred in a known swarm area, and six earthquakes (43%) were random occurrences. No earthquakes triggered the Hanford Strong Motion Accelerometer during the first quarter of FY99.

Hanford: A Conversation About Nuclear Waste and Cleanup

International Nuclear Information System (INIS)

Gephart, Roy E.

2003-01-01

The author takes us on a journey through a world of facts, values, conflicts, and choices facing the most complex environmental cleanup project in the United States, the U.S. Department of Energy's Hanford Site. Starting with the top-secret Manhattan Project, Hanford was used to create tons of plutonium for nuclear weapons. Hundreds of tons of waste remain. In an easy-to-read, illustrated text, Gephart crafts the story of Hanford becoming the world's first nuclear weapons site to release large amounts of contaminants into the environment. This was at a time when radiation biology was in its infancy, industry practiced unbridled waste dumping, and the public trusted what it was told. The plutonium market stalled with the end of the Cold War. Public accountability and environmental compliance ushered in a new cleanup mission. Today, Hanford is driven by remediation choices whose outcomes remain uncertain. It's a story whose epilogue will be written by future generations. This book is an information resource, written for the general reader as well as the technically trained person wanting an overview of Hanford and cleanup issues facing the nuclear weapons complex. Each chapter is a topical mini-series. It's an idea guide that encourages readers to be informed consumers of Hanford news, to recognize that knowledge, high ethical standards, and social values are at the heart of coping with Hanford's past and charting its future. Hanford history is a window into many environmental conflicts facing our nation; it's about building upon success and learning from failure. And therein lies a key lesson, when powerful interests are involved, no generation is above pretense. Roy E. Gephart is a geohydrologist and senior program manager at the Pacific Northwest National Laboratory, Richland, Washington. He has 30 years experience in environmental studies and the nuclear waste industry

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

Energy Technology Data Exchange (ETDEWEB)

Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

2015-11-27

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

FINAL FRONTIER AT HANFORD TACKLING THE CENTRAL PLATEAU

International Nuclear Information System (INIS)

GERBER MS

2008-01-01

The large land area in the center of the vast Department of Energy (DOE) Hanford Site in southeast Washington State is known as 'the plateau'--aptly named because its surface elevations are 250-300 feet above the groundwater table. By contrast, areas on the 585-square mile Site that border the Columbia River sit just 30-80 feet above the water table. The Central Plateau, which covers an ellipse of approximately 70 square miles, contains Hanford's radiochemical reprocessing areas--the 200 East and 200 West Areas--and includes the most highly radioactive waste and contaminated facilities on the Site. Five 'canyons' where chemical processes were used to separate out plutonium (Pu), 884 identified soil waste sites (including approximately 50 miles of solid waste burial trenches), more than 900 structures, and all of Hanford's liquid waste storage tanks reside in the Central Plateau. (Notes: Canyons is a nickname given by Hanford workers to the chemical reprocessing facilities. The 177, underground waste tanks at Hanford comprise a separate work scope and are not under Fluor's management). Fluor Hanford, a DOE prime cleanup contractor at the Site for the past 12 years, has moved aggressively to investigate Central Plateau waste sites in the last few years, digging more than 500 boreholes, test pits, direct soil 'pushes' or drive points; logging geophysical data sets; and performing electrical-resistivity scans (a non-intrusive technique that maps patterns of sub-surface soil conductivity). The goal is to identify areas of contamination areas in soil and solid waste sites, so that cost-effective and appropriate decisions on remediation can be made. In 2007, Fluor developed a new work plan for DOE that added 238 soil waste-site characterization activities in the Central Plateau during fiscal years (FYs) 2007-2010. This number represents a 50 percent increase over similar work previously done in central Hanford. Work Plans are among the required steps in the Comprehensive

Seismic qualification of safety class components in non-reactor nuclear facilities at Hanford site

International Nuclear Information System (INIS)

Ocoma, E.C.

1989-01-01

This paper presents the methods used during the walkdowns to compile as-built structural information to seismically qualify or verify the seismic adequacy of safety class components in the Plutonium Finishing Plant complex. The Plutonium finishing Plant is a non-reactor nuclear facility built during the 1950's and was designed to the Uniform Building Code criteria for both seismic and wind events. This facility is located at the US Department of Energy Hanford Site near Richland, Washington

Regulation of the Nampt-mediated NAD salvage pathway and its therapeutic implications in pancreatic cancer.

Science.gov (United States)

Ju, Huai-Qiang; Zhuang, Zhuo-Nan; Li, Hao; Tian, Tian; Lu, Yun-Xin; Fan, Xiao-Qiang; Zhou, Hai-Jun; Mo, Hai-Yu; Sheng, Hui; Chiao, Paul J; Xu, Rui-Hua

2016-08-28

Nicotinamide adenine dinucleotide (NAD) is a crucial cofactor for the redox reactions in the metabolic pathways of cancer cells that have elevated aerobic glycolysis (Warburg effect). Cancer cells are reported to rely on NAD recycling and inhibition of the NAD salvage pathway causes metabolic collapse and cell death. However, the underlying regulatory mechanisms and clinical implications for the NAD salvage pathway in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study showed that the expression of Nampt, the rate-limiting enzyme of the NAD salvage pathway, was significantly increased in PDAC cells and PDAC tissues. Additionally, inhibition of Nampt impaired tumor growth in vitro and tumorigenesis in vivo, which was accompanied by a decreased cellular NAD level and glycolytic activity. Mechanistically, the Nampt expression was independent of Kras and p16 status, but it was directly regulated by miR-206, which was inversely correlated with the expression of Nampt in PDAC tissues. Importantly, pharmacological inhibition of Nampt by its inhibitor, FK866, significantly enhanced the antitumor activity of gemcitabine in PDAC cells and in orthotopic xenograft mouse models. In conclusion, the present study revealed a novel regulatory mechanism for Nampt in PDAC and suggested that Nampt inhibition may override gemcitabine resistance by decreasing the NAD level and suppressing glycolytic activity, warranting further clinical investigation for pancreatic cancer treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Criteria impacting shipments of Rocky Flats Plant radioactive mixed wastes

International Nuclear Information System (INIS)

Clawson, R.L.; Eide, J.H.

1992-05-01

Westinghouse Hanford Company, Transportation and Packaging Division, under contract for the Los Alamos Technology Office-Rocky Flats Plant, has developed this synopsis report to be used as a reference in the development of the Rocky Flats Plant Comprehensive Treatment and Management Plan and the Rocky Flats Plant Residue Elimination Plan. This report represents the criteria for packaging, shipping, and transporting Rocky Flats Plant radioactive mixed wastes. It is a compilation of state and federal regulations, US Department of Energy orders, and acceptance criteria specific to US Department of Energy radioactive mixed waste treatment, storage and disposal facilities

Second Quarter Hanford Seismic Report for Fiscal Year 2000

International Nuclear Information System (INIS)

Hartshorn, D.C.; Reidel, S.P.; Rohay, A.C.

2000-01-01

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the US Department of Energy and its contractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (EWRN) consist of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The HSN uses 21 sites and the EWRN uses 36 sites; both networks share 16 sites. The networks have 46 combined data channels because Gable Butte and Frenchman Hills East are three-component sites. The reconfiguration of the telemetry and recording systems was completed during the first quarter. All leased telephone lines have been eliminated and radio telemetry is now used exclusively. For the HSN, there were 506 triggers on two parallel detection and recording systems during the second quarter of fiscal year (FY) 2000. Twenty-seven seismic events were located by the Hanford Seismic Network within the reporting region of 46--47degree N latitude and 119--120degree W longitude; 12 were earthquakes in the Columbia River Basalt Group, 2 were earthquakes in the pre-basalt sediments, 9 were earthquakes in the crystalline basement, and 5 were quarry blasts. Three earthquakes appear to be related to geologic structures, eleven earthquakes occurred in known swarm areas, and seven earthquakes were random occurrences. No earthquakes triggered the Hanford Strong Motion

Second Quarter Hanford Seismic Report for Fiscal Year 2000

Energy Technology Data Exchange (ETDEWEB)

DC Hartshorn; SP Reidel; AC Rohay

2000-07-17

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the US Department of Energy and its contractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (EWRN) consist of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The HSN uses 21 sites and the EWRN uses 36 sites; both networks share 16 sites. The networks have 46 combined data channels because Gable Butte and Frenchman Hills East are three-component sites. The reconfiguration of the telemetry and recording systems was completed during the first quarter. All leased telephone lines have been eliminated and radio telemetry is now used exclusively. For the HSN, there were 506 triggers on two parallel detection and recording systems during the second quarter of fiscal year (FY) 2000. Twenty-seven seismic events were located by the Hanford Seismic Network within the reporting region of 46--47{degree} N latitude and 119--120{degree} W longitude; 12 were earthquakes in the Columbia River Basalt Group, 2 were earthquakes in the pre-basalt sediments, 9 were earthquakes in the crystalline basement, and 5 were quarry blasts. Three earthquakes appear to be related to geologic structures, eleven earthquakes occurred in known swarm areas, and seven earthquakes were random occurrences. No earthquakes triggered the Hanford Strong Motion

First quarter Hanford seismic report for fiscal year 2000

Energy Technology Data Exchange (ETDEWEB)

DC Hartshorn; SP Reidel; AC Rohay

2000-02-23

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the US Department of Energy and its contractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (EWRN) consist of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The HSN uses 21 sites and the EW uses 36 sites; both networks share 16 sites. The networks have 46 combined data channels because Gable Butte and Frenchman Hills East are three-component sites. The reconfiguration of the telemetry and recording systems was completed during the first quarter. All leased telephone lines have been eliminated and radio telemetry is now used exclusively. For the HSN, there were 311 triggers on two parallel detection and recording systems during the first quarter of fiscal year (FY) 2000. Twelve seismic events were located by the Hanford Seismic Network within the reporting region of 46--47{degree}N latitude and 119--120{degree}W longitude; 2 were earthquakes in the Columbia River Basalt Group, 3 were earthquakes in the pre-basalt sediments, 9 were earthquakes in the crystalline basement, and 1 was a quarry blast. Two earthquakes appear to be related to a major geologic structure, no earthquakes occurred in known swarm areas, and 9 earthquakes were random occurrences. No earthquakes triggered the Hanford Strong Motion Accelerometers

Hanford Site National Environmental Policy Act (NEPA) Characterization

Energy Technology Data Exchange (ETDEWEB)

Neitzel, Duane A.; Antonio, Ernest J.; Eschbach, Tara O.; Fowler, Richard A.; Goodwin, Shannon M.; Harvey, David W.; Hendrickson, Paul L.; Hoitink, Dana J.; Horton, Duane G.; Last, George V.; Poston, Ted M.; Prendergast, Ellen L.; Rohay, Alan C.; Thorne, Paul D.

2001-09-01

This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities.

Hanford Site National Environmental Policy Act (NEPA) Characterization

Energy Technology Data Exchange (ETDEWEB)

Neitzel, Duane A.; Bunn, Amoret L.; Duncan, Joanne P.; Eschbach, Tara O.; Fowler, Richard A.; Fritz, Brad G.; Goodwin, Shannon M.; Harvey, David W.; Hendrickson, Paul L.; Hoitink, Dana J.; Horton, Duane G.; Last, George V.; Poston, Ted M.; Prendergast-Kennedy, Ellen L.; Rohay, Alan C.; Scott, Michael J.; Thorne, Paul D.

2002-09-01

This document describes the U.S. Department of Energy's (DOE) Hanford Site environment. It is updated each year and is intended to provide a consistent description of the Hanford Site environment for the many National Environmental Policy Act (NEPA) documents being prepared by DOE contractors. No statements of significance or environmental consequences are provided. This year's report is the thirteenth revision of the original document published in 1988 and is (until replaced by the fourteenth revision) the only version that is relevant for use in the preparation of Hanford NEPA, State Environmental Policy Act (SEPA), and Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) documents. The two chapters included in this document (Chapters 4 and 6) are numbered to correspond to the chapters where such information is typically presented in environmental impact statements (Weiss) and other Hanford Site NEPA or CERCLA documentation. Chapter 4.0 (Affected Environment) describes Hanford Site climate and meteorology, geology, hydrology, ecology, cultural, archaeological, and historical resources, socioeconomics, occupational safety, and noise. Chapter 6.0 (Statutory and Regulatory Requirements) describes federal and state laws and regulations, DOE directives and permits, and presidential executive orders that are applicable to the NEPA documents prepared for Hanford Site activities.

CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

Science.gov (United States)

Camacho-Pereira, Juliana; Tarragó, Mariana G; Chini, Claudia C S; Nin, Veronica; Escande, Carlos; Warner, Gina M; Puranik, Amrutesh S; Schoon, Renee A; Reid, Joel M; Galina, Antonio; Chini, Eduardo N

2016-06-14

Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Hanford process review

International Nuclear Information System (INIS)

1991-12-01

This report is a summary of past incidents at the US Department of Energy's (DOE) Hanford Site. The purpose of the report is to provide the major, significant, nuclear-safety-related incidents which incurred at the Hanford Site in a single document for ease of historical research. It should be noted that the last major accident occurred in 1980. This document is a summary of reports released and available to the public in the DOE Headquarters and Richland public reading rooms. This document provides no new information that has not previously been reported. This report is not intended to cover all instances of radioactivity release or contamination, which are already the subject of other major reviews, several of which are referenced in Section 1.3

High-resolution crystal structures of the photoreceptor glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with three and four-bound NAD molecules

Science.gov (United States)

Baker, Bo Y; Shi, Wuxian; Wang, Benlian; Palczewski, Krzysztof

2014-01-01

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalyzes the oxidative phosphorylation of d-glyceraldehyde 3-phosphate (G3P) into 1,3-diphosphoglycerate (BGP) in the presence of the NAD cofactor. GAPDH is an important drug target because of its central role in glycolysis, and nonglycolytic processes such as nuclear RNA transport, DNA replication/repair, membrane fusion and cellular apoptosis. Recent studies found that GAPDH participates in the development of diabetic retinopathy and its progression after the cessation of hyperglycemia. Here, we report two structures for native bovine photoreceptor GAPDH as a homotetramer with differing occupancy by NAD, bGAPDH(NAD)4, and bGAPDH(NAD)3. The bGAPDH(NAD)4 was solved at 1.52 Å, the highest resolution for GAPDH. Structural comparison of the bGAPDH(NAD)4 and bGAPDH(NAD)3 models revealed novel details of conformational changes induced by cofactor binding, including a loop region (residues 54–56). Structure analysis of bGAPDH confirmed the importance of Phe34 in NAD binding, and demonstrated that Phe34 was stabilized in the presence of NAD but displayed greater mobility in its absence. The oxidative state of the active site Cys149 residue is regulated by NAD binding, because this residue was found oxidized in the absence of dinucleotide. The distance between Cys149 and His176 decreased upon NAD binding and Cys149 remained in a reduced state when NAD was bound. These findings provide an important structural step for understanding the mechanism of GAPDH activity in vision and its pathological role in retinopathies. PMID:25176140

Hanford tank initiative test facility site selection study

International Nuclear Information System (INIS)

Staehr, T.W.

1997-01-01

The Hanford Tanks Initiative (HTI) project is developing equipment for the removal of hard heel waste from the Hanford Site underground single-shell waste storage tanks. The HTI equipment will initially be installed in the 241-C-106 tank where its operation will be demonstrated. This study evaluates existing Hanford Site facilities and other sites for functional testing of the HTI equipment before it is installed into the 241-C-106 tank

Nicotinamide riboside kinase structures reveal new pathways to NAD+.

Directory of Open Access Journals (Sweden)

Wolfram Tempel

2007-10-01

Full Text Available The eukaryotic nicotinamide riboside kinase (Nrk pathway, which is induced in response to nerve damage and promotes replicative life span in yeast, converts nicotinamide riboside to nicotinamide adenine dinucleotide (NAD+ by phosphorylation and adenylylation. Crystal structures of human Nrk1 bound to nucleoside and nucleotide substrates and products revealed an enzyme structurally similar to Rossmann fold metabolite kinases and allowed the identification of active site residues, which were shown to be essential for human Nrk1 and Nrk2 activity in vivo. Although the structures account for the 500-fold discrimination between nicotinamide riboside and pyrimidine nucleosides, no enzyme feature was identified to recognize the distinctive carboxamide group of nicotinamide riboside. Indeed, nicotinic acid riboside is a specific substrate of human Nrk enzymes and is utilized in yeast in a novel biosynthetic pathway that depends on Nrk and NAD+ synthetase. Additionally, nicotinic acid riboside is utilized in vivo by Urh1, Pnp1, and Preiss-Handler salvage. Thus, crystal structures of Nrk1 led to the identification of new pathways to NAD+.

HANFORD WASTE MINEROLOGY REFERENCE REPORT

International Nuclear Information System (INIS)

Disselkamp, R.S.

2010-01-01

This report lists the observed mineral phases present in the Hanford tanks. This task was accomplished by performing a review of numerous reports using experimental techniques including, but not limited to: x-ray diffraction, polarized light microscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, electron energy loss spectroscopy, and particle size distribution analyses. This report contains tables that can be used as a quick reference to identify the crystal phases present observed in Hanford waste.

Hanford Waste Mineralogy Reference Report

International Nuclear Information System (INIS)

Disselkamp, R.S.

2010-01-01

This report lists the observed mineral phases present in the Hanford tanks. This task was accomplished by performing a review of numerous reports that used experimental techniques including, but not limited to: x-ray diffraction, polarized light microscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, electron energy loss spectroscopy, and particle size distribution analyses. This report contains tables that can be used as a quick reference to identify the crystal phases observed in Hanford waste.

HANFORD WASTE MINERALOGY REFERENCE REPORT

Energy Technology Data Exchange (ETDEWEB)

DISSELKAMP RS

2010-06-29

This report lists the observed mineral phases present in the Hanford tanks. This task was accomplished by performing a review of numerous reports that used experimental techniques including, but not limited to: x-ray diffraction, polarized light microscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, electron energy loss spectroscopy, and particle size distribution analyses. This report contains tables that can be used as a quick reference to identify the crystal phases observed in Hanford waste.

HANFORD WASTE MINEROLOGY REFERENCE REPORT

Energy Technology Data Exchange (ETDEWEB)

DISSELKAMP RS

2010-06-18

This report lists the observed mineral phase phases present in the Hanford tanks. This task was accomplished by performing a review of numerous reports using experimental techniques including, but not limited to: x-ray diffraction, polarized light microscopy, scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, electron energy loss spectroscopy, and particle size distribution analyses. This report contains tables that can be used as a quick reference to identify the crystal phases present observed in Hanford waste.

Technology Evaluation for Conditioning of Hanford Tank Waste Using Solids Segregation and Size Reduction

Energy Technology Data Exchange (ETDEWEB)

Restivo, Michael L.; Stone, M. E.; Herman, D. T.; Lambert, Daniel P.; Duignan, Mark R.; Smith, Gary L.; Wells, Beric E.; Lumetta, Gregg J.; Enderlin, Carl W.; Adkins, Harold E.

2014-04-24

The Savannah River National Laboratory and the Pacific Northwest National Laboratory team performed a literature search on current and proposed technologies for solids segregation and size reduction of particles in the slurry feed from the Hanford Tank Farm. The team also investigated technology research performed on waste tank slurries, both real and simulated, and reviewed academic theory applicable to solids segregation and size reduction. This review included text book applications and theory, commercial applications suitable for a nuclear environment, research of commercial technologies suitable for a nuclear environment, and those technologies installed in a nuclear environment, including technologies implemented at Department of Energy facilities. Information on each technology is provided in this report along with the advantages and disadvantages of the technologies for this application. Any technology selected would require testing to verify the ability to meet the High-Level Waste Feed Waste Acceptance Criteria to the Hanford Tank Waste Treatment and Immobilization Plant Pretreatment Facility.

FLUOR HANFORD SAFETY MANAGEMENT PROGRAMS

Energy Technology Data Exchange (ETDEWEB)

GARVIN, L. J.; JENSEN, M. A.

2004-04-13

This document summarizes safety management programs used within the scope of the ''Project Hanford Management Contract''. The document has been developed to meet the format and content requirements of DOE-STD-3009-94, ''Preparation Guide for US. Department of Energy Nonreactor Nuclear Facility Documented Safety Analyses''. This document provides summary descriptions of Fluor Hanford safety management programs, which Fluor Hanford nuclear facilities may reference and incorporate into their safety basis when producing facility- or activity-specific documented safety analyses (DSA). Facility- or activity-specific DSAs will identify any variances to the safety management programs described in this document and any specific attributes of these safety management programs that are important for controlling potentially hazardous conditions. In addition, facility- or activity-specific DSAs may identify unique additions to the safety management programs that are needed to control potentially hazardous conditions.

Software configuration management plan for the Hanford site technical database

International Nuclear Information System (INIS)

GRAVES, N.J.

1999-01-01

The Hanford Site Technical Database (HSTD) is used as the repository/source for the technical requirements baseline and programmatic data input via the Hanford Site and major Hanford Project Systems Engineering (SE) activities. The Hanford Site SE effort has created an integrated technical baseline for the Hanford Site that supports SE processes at the Site and project levels which is captured in the HSTD. The HSTD has been implemented in Ascent Logic Corporation (ALC) Commercial Off-The-Shelf (COTS) package referred to as the Requirements Driven Design (RDD) software. This Software Configuration Management Plan (SCMP) provides a process and means to control and manage software upgrades to the HSTD system

75 FR 6018 - Environmental Management Site-Specific Advisory Board, Hanford

Science.gov (United States)

2010-02-05

... DEPARTMENT OF ENERGY Environmental Management Site-Specific Advisory Board, Hanford AGENCY... Environmental Management Site-Specific Advisory Board (EM SSAB), Hanford (known locally as the Hanford Advisory... and site management in the areas of environmental restoration, waste management, and related...

Environmental surveillance at Hanford for CY-1974

International Nuclear Information System (INIS)

Fix, J.J.

1975-04-01

During 1974, the work at Hanford included N Reactor operation, nuclear fuel fabrication, liquid waste solidification, continued construction of the Fast Flux Test Facility, continued construction of Washington Public Power Supply System (WPPSS) No. 2 power reactor, Arid Lands Ecology studies, as well as continued use of a variety of research and laboratory facilities. Environmental data collected during 1974 showed continued compliance of Hanford operations with all applicable state and federal regulations. Levels of radioactivity in the atmosphere from Hanford operations at all offsite sampling locations were indistinguishable from levels due to natural causes and fallout from nuclear detonations in the atmosphere. Air quality measurements of NO 2 in the Hanford environs recorded a maximum yearly average concentration of 0.006 ppM or 12 percent of the ambient air standard. There was no indication that Hanford operations contributed significantly to these levels. All SO 2 results were less than the detection limit of 0.005 ppM or 25 percent of the ambient air quality standard. Routine radiological, chemical, biological, and physical analyses of Columbia River water upstream and downstream of the Hanford Reservation operations with the possible exception of water temperature. Levels of radioactivity were similar at both locations and were due to natural and fallout radioactivity. Estimates are included of the radiation dose to the human population within an 80-kilometer (50-mile) radius of the site during 1974. Methods used in calculations of the annual dose and 50-year dose commitment from radioactive effluents are discussed. (U.S.)

THE IMPACT OF SHRINKING HANFORD BOUNDARIES ON PERMITS FOR TOXIC AIR POLLUTANT EMISSIONS FROM THE HANFORD 200 WEST AREA

International Nuclear Information System (INIS)

JOHNSON, R.E.

2005-01-01

This presentation (CE-580. Graduate Seminar) presents a brief description of an approach to use a simpler dispersion modeling method (SCREEN3) in conjunction with joint frequency tables for Hanford wind conditions to evaluate the impacts of shrinking the Hanford boundaries on the current permits for facilities in the 200 West Area. To fulfill requirements for the graduate student project (CE-702. Master's Special Problems), this evaluation will be completed and published over the next two years. Air toxic emissions play an important role in environmental quality and require a state approved permit. One example relates to containers or waste that are designated as Transuranic Waste (TRU), which are required to have venting devices due to hydrogen generation. The Washington State Department of Ecology (Ecology) determined that the filters used did not meet the definition of a ''pressure relief device'' and that a permit application would have to be submitted by the Central Waste Complex (CWC) for criteria pollutant and toxic air pollutant (TAP) emissions in accordance with Washington Administrative Code (WAC) 173-400 and 173-460. The permit application submitted in 2000 to Ecology used Industrial Source Code III (ISCIII) dispersion modeling to demonstrate that it was not possible for CWC to release a sufficient quantity of fugitive Toxic Air Pollutant emissions that could exceed the Acceptable Source Impact Levels (ASILs) at the Hanford Site Boundary. The modeled emission rates were based on the diurnal breathing in and out through the vented drums (approximately 20% of the drums), using published vapor pressure, molecular weight, and specific gravity data for all 600+ compounds, with a conservative estimate of one exchange volume per day (208 liters per drum). Two permit applications were submitted also to Ecology for the Waste Receiving and Processing Facility and the T Plant Complex. Both permit applications were based on the Central Waste Complex approach, and

Deficiency of the Mitochondrial NAD Kinase Causes Stress-Induced Hepatic Steatosis in Mice

NARCIS (Netherlands)

Zhang, Kezhong; Kim, Hyunbae; Fu, Zhiyao; Qiu, Yining; Yang, Zhao; Wang, Jiemei; Zhang, Deqiang; Tong, Xin; Yin, Lei; Li, Jing; Wu, Jianmei; Qi, Nathan R.; Houten, Sander M.; Zhang, Ren

2018-01-01

The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (NADK2, also called MNADK) catalyzes phosphorylation of NAD to yield NADP. Little is known about the functions of mitochondrial NADP and MNADK in liver physiology and pathology. We investigated the effects of reduced mitochondrial NADP

NAD+ Deficits in Age-Related Diseases and Cancer.

Science.gov (United States)

Garrido, Amanda; Djouder, Nabil

2017-08-01

The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD + reduction as the central mechanism that may connect aging to its related pathologies and cancer. NAD + boosters would ensure and ameliorate health quality during aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Hanford: The evolution of a dinosaur

International Nuclear Information System (INIS)

Fulton, J.

1995-01-01

This article describes how the Westinghouse Hanford Company is reinventing the US DOE's Hanford Site, turning a 1940s-era dinosaur into a 1990s-style business. The major topics covered include the following: breaking the logjam by ending the inefficient cost-plus days; Concentrating resources on resolving urgent safety issues; contract reform with more incentive, greater risk; finally reengineering: the next step

Theophylline prevents NAD+ depletion via PARP-1 inhibition in human pulmonary epithelial cells

International Nuclear Information System (INIS)

Moonen, Harald J.J.; Geraets, Liesbeth; Vaarhorst, Anika; Bast, Aalt; Wouters, Emiel F.M.; Hageman, Geja J.

2005-01-01

Oxidative DNA damage, as occurs during exacerbations in chronic obstructive pulmonary disease (COPD), highly activates the nuclear enzyme poly(ADP-ribose)polymerase-1 (PARP-1). This can lead to cellular depletion of its substrate NAD + , resulting in an energy crisis and ultimately in cell death. Inhibition of PARP-1 results in preservation of the intracellular NAD + pool, and of NAD + -dependent cellular processes. In this study, PARP-1 activation by hydrogen peroxide decreased intracellular NAD + levels in human pulmonary epithelial cells, which was found to be prevented in a dose-dependent manner by theophylline, a widely used compound in the treatment of COPD. This enzyme inhibition by theophylline was confirmed in an ELISA using purified human PARP-1 and was found to be competitive by nature. These findings provide new mechanistic insights into the therapeutic effect of theophylline in oxidative stress-induced lung pathologies

Hanford Waste Vitrification Plant applied technology plan

International Nuclear Information System (INIS)

Kruger, O.L.

1990-09-01

This Applied Technology Plan describes the process development, verification testing, equipment adaptation, and waste form qualification technical issues and plans for resolution to support the design, permitting, and operation of the Hanford Waste Vitrification Plant. The scope of this Plan includes work to be performed by the research and development contractor, Pacific Northwest Laboratory, other organizations within Westinghouse Hanford Company, universities and companies with glass technology expertise, and other US Department of Energy sites. All work described in this Plan is funded by the Hanford Waste Vitrification Plant Project and the relationship of this Plan to other waste management documents and issues is provided for background information. Work to performed under this Plan is divided into major areas that establish a reference process, develop an acceptable glass composition envelope, and demonstrate feed processing and glass production for the range of Hanford Waste Vitrification Plant feeds. Included in this work is the evaluation and verification testing of equipment and technology obtained from the Defense Waste Processing Facility, the West Valley Demonstration Project, foreign countries, and the Hanford Site. Development and verification of product and process models and other data needed for waste form qualification documentation are also included in this Plan. 21 refs., 4 figs., 33 tabs

Hanford facility dangerous waste permit application

International Nuclear Information System (INIS)

1991-01-01

This document, Set 2, the Hanford Facility Dangerous Waste Part B Permit Application, consists of 15 chapters that address the content of the Part B checklists prepared by the Washington State Department of Ecology (Ecology 1987) and the US Environmental Protection Agency (40 CFR 270), with additional information requirements mandated by the Hazardous and Solid Waste Amendments of 1984 and revisions of WAC 173-303. For ease of reference, the Washington State Department of Ecology checklist section numbers, in brackets, follow the chapter headings and subheadings. This permit application contains ''umbrella- type'' documentation with overall application to the Hanford Facility. This documentation is broad in nature and applies to all TSD units that have final status under the Hanford Facility Permit

The Hanford summit and sustainable development

International Nuclear Information System (INIS)

Sullivan, C.T.

1994-05-01

Since the days of the Manhattan Project of World War II, the economic well being of the Tri-Cities (Pasco, Kennewick, and Richland) of Washington State has been tied to the US Department of Energy missions at the nearby Hanford Site. As missions at the Site changed, so did the well being of the region. The Hanford Site is now poised to complete its final mission, that of environmental restoration. When restoration is compiled, the Site may be closed and the effect on the local economy will be devastating if action is not taken now. To that end, economic diversification and transition are being planned. To facilitate the process, the Hanford Site will become a sustainable development demonstration project -- a project with regional, national, and international application

Management of Hanford Site non-defense production reactor spent nuclear fuel, Hanford Site, Richland, Washington

International Nuclear Information System (INIS)

1997-03-01

The US Department of Energy (DOE) needs to provide radiologically, and industrially safe and cost-effective management of the non-defense production reactor spent nuclear fuel (SNF) at the Hanford Site. The proposed action would place the Hanford Site's non-defense production reactor SNF in a radiologically- and industrially-safe, and passive storage condition pending final disposition. The proposed action would also reduce operational costs associated with storage of the non-defense production reactor SNF through consolidation of the SNF and through use of passive rather than active storage systems. Environmental, safety and health vulnerabilities associated with existing non-defense production reactor SNF storage facilities have been identified. DOE has determined that additional activities are required to consolidate non-defense production reactor SNF management activities at the Hanford Site, including cost-effective and safe interim storage, prior to final disposition, to enable deactivation of facilities where the SNF is now stored. Cost-effectiveness would be realized: through reduced operational costs associated with passive rather than active storage systems; removal of SNF from areas undergoing deactivation as part of the Hanford Site remediation effort; and eliminating the need to duplicate future transloading facilities at the 200 and 400 Areas. Radiologically- and industrially-safe storage would be enhanced through: (1) removal from aging facilities requiring substantial upgrades to continue safe storage; (2) utilization of passive rather than active storage systems for SNF; and (3) removal of SNF from some storage containers which have a limited remaining design life. No substantial increase in Hanford Site environmental impacts would be expected from the proposed action. Environmental impacts from postulated accident scenarios also were evaluated, and indicated that the risks associated with the proposed action would be small

Second and Third Quarters Hanford Seismic Report for Fiscal Year 1999

Energy Technology Data Exchange (ETDEWEB)

Hartshorn, Donald C.; Reidel, Stephen P.; Rohay, Alan C.

1999-10-08

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the U.S. Department of Energy and its contractors. Hanford Seismic Monitoring also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the Hanford Site.

A high effective NADH-ferricyanide dehydrogenase coupled with laccase for NAD(+) regeneration.

Science.gov (United States)

Wang, Jizhong; Yang, Chengli; Chen, Xing; Bao, Bingxin; Zhang, Xuan; Li, Dali; Du, Xingfan; Shi, Ruofu; Yang, Junfang; Zhu, Ronghui

2016-08-01

To find an efficient and cheap system for NAD(+) regeneration A NADH-ferricyanide dehydrogenase was obtained from an isolate of Escherichia coli. Optimal activity of the NADH dehydrogenase was at 45 °C and pH 7.5, with a K m value for NADH of 10 μM. By combining the NADH dehydrogenase, potassium ferricyanide and laccase, a bi-enzyme system for NAD(+) regeneration was established. The system is attractive in that the O2 consumed by laccase is from air and the sole byproduct of the reaction is water. During the reaction process, 10 mM NAD(+) was transformed from NADH in less than 2 h under the condition of 0.5 U NADH dehydrogenase, 0.5 U laccase, 0.1 mM potassium ferricyanide at pH 5.6, 30 °C CONCLUSION: The bi-enzyme system employed the NADH-ferricyanide dehydrogenase and laccase as catalysts, and potassium ferricyanide as redox mediator, is a promising alternative for NAD(+) regeneration.

Hanford Environmental Dose Reconstruction Project

International Nuclear Information System (INIS)

Cannon, S.D.; Finch, S.M.

1992-10-01

The objective of the Hanford Environmental Dose Reconstruction (HEDR) Project is to estimate the radiation doses that individuals and populations could have received from nuclear operations at Hanford since 1944. The independent Technical Steering Panel (TSP) provides technical direction. The project is divided into the following technical tasks. These tasks correspond to the path radionuclides followed from release to impact on humans (dose estimates):Source Terms, Environmental Transport, Environmental Monitoring Data, Demography, Food Consumption, and Agriculture, and Environmental Pathways and Dose Estimates

Application of NAD(P)H oxidase for cofactor regeneration in dehydrogenase catalyzed oxidations

DEFF Research Database (Denmark)

Rehn, Gustav; Pedersen, Asbjørn Toftgaard; Woodley, John

2016-01-01

alcohol dehydrogenases. However, their effective use requires an effective regeneration of the oxidized nicotinamide cofactor (NAD(P)+), which is critical for the economic feasibility of the process. NAD(P)H oxidase is an enzyme class of particular interest for this cofactor regeneration since it enables...

Audit Report on 'Waste Processing and Recovery Act Acceleration Efforts for Contact-Handled Transuranic Waste at the Hanford Site'

International Nuclear Information System (INIS)

2010-01-01

The Department of Energy's Office of Environmental Management's (EM), Richland Operations Office (Richland), is responsible for disposing of the Hanford Site's (Hanford) transuranic (TRU) waste, including nearly 12,000 cubic meters of radioactive contact-handled TRU wastes. Prior to disposing of this waste at the Department's Waste Isolation Pilot Plant (WIPP), Richland must certify that it meets WIPP's waste acceptance criteria. To be certified, the waste must be characterized, screened for prohibited items, treated (if necessary) and placed into a satisfactory disposal container. In a February 2008 amendment to an existing Record of Decision (Decision), the Department announced its plan to ship up to 8,764 cubic meters of contact-handled TRU waste from Hanford and other waste generator sites to the Advanced Mixed Waste Treatment Project (AMWTP) at Idaho's National Laboratory (INL) for processing and certification prior to disposal at WIPP. The Department decided to maximize the use of the AMWTP's automated waste processing capabilities to compact and, thereby, reduce the volume of contact-handled TRU waste. Compaction reduces the number of shipments and permits WIPP to more efficiently use its limited TRU waste disposal capacity. The Decision noted that the use of AMWTP would avoid the time and expense of establishing a processing capability at other sites. In May 2009, EM allocated $229 million of American Recovery and Reinvestment Act of 2009 (Recovery Act) funds to support Hanford's Solid Waste Program, including Hanford's contact-handled TRU waste. Besides providing jobs, these funds were intended to accelerate cleanup in the short term. We initiated this audit to determine whether the Department was effectively using Recovery Act funds to accelerate processing of Hanford's contact-handled TRU waste. Relying on the availability of Recovery Act funds, the Department changed course and approved an alternative plan that could increase costs by about $25 million

Temporal variations in atmospheric dispersion at Hanford

International Nuclear Information System (INIS)

Ramsdell, J.V.; Burk, K.W.

1990-01-01

Climatological data are frequently used to estimate atmospheric dispersion factors for historical periods and for future releases for which adequate meteorological data are unavailable. This practice routinely leads to questions concerning the representativeness of data used. The work described here was performed to provide a basis for answering these questions at the U.S. Department of Energy's Hanford Site in eastern Washington. Atmospheric transport and diffusion near Hanford have been examined using a Lagrangian puff dispersion model and hourly meteorological data from the Hanford Meteorological Station and a network of 24 surface wind stations for a 5-yr period. Average normalized monthly concentrations were computed at 2.5-km intervals on a 31 by 31 grid from January 1983 through 1987, assuming an elevated release in the 200-East Area. Monthly average concentrations were used to determine 5-yr mean pattern and monthly mean patterns and the interannual variability about each pattern. Intra-annual and diurnal variations in dispersion factors are examined for six locations near Hanford

Accelerated clean-up at the Hanford Site

International Nuclear Information System (INIS)

Frain, J.M.; Johnson, W.L.

1994-01-01

The Hanford Site began operations in 1943 as one of the sites for plutonium production associated with the Manhattan Project. It has been used, in part, for nuclear reactor operation, reprocessing of spent fuel, and management of radioactive waste. The Hanford Site covers approximately 1,434 km 2 (560 mi 2 2) in southeastern Washington State. The subject of this paper, the 618-9 Burial Ground, is located on the Hanford Site approximately 1.6 km (1 mi) west of the Columbia River, and a few miles north of Richland, Washington. Throughout Hanford Site history, prior to legislation regarding disposal of chemical waste products, some chemical waste byproducts were disposed ,ia burial in trenches. One such trench was the 618-9 Burial Ground. This burial ground was suspected to contain approximately 19,000 L (5,000 gal) of uranium-contaminated organic solvent, disposed in standard 55-gal (208-L) metal drums. The waste was produced from research and development activities related to fuel reprocessing

An NAD+-dependent transcriptional program governs self-renewal and radiation resistance in glioblastoma.

Science.gov (United States)

Gujar, Amit D; Le, Son; Mao, Diane D; Dadey, David Y A; Turski, Alice; Sasaki, Yo; Aum, Diane; Luo, Jingqin; Dahiya, Sonika; Yuan, Liya; Rich, Keith M; Milbrandt, Jeffrey; Hallahan, Dennis E; Yano, Hiroko; Tran, David D; Kim, Albert H

2016-12-20

Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD + ). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD + synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD + levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD + -dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD + metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.

Hanford spent nuclear fuel project update

Energy Technology Data Exchange (ETDEWEB)

Williams, N.H.

1997-08-19

Twenty one hundred metric tons of spent nuclear fuel (SNF) are currently stored in the Hanford Site K Basins near the Columbia River. The deteriorating conditions of the fuel and the basins provide engineering and management challenges to assure safe current and future storage. DE and S Hanford, Inc., part of the Fluor Daniel Hanford, Inc. lead team on the Project Hanford Management Contract, is constructing facilities and systems to move the fuel from current pool storage to a dry interim storage facility away from the Columbia River, and to treat and dispose of K Basins sludge, debris and water. The process starts in K Basins where fuel elements will be removed from existing canisters, washed, and separated from sludge and scrap fuel pieces. Fuel elements will be placed in baskets and loaded into Multi-Canister Overpacks (MCOs) and into transportation casks. The MCO and cask will be transported to the Cold Vacuum Drying Facility, where free water within the MCO will be removed under vacuum at slightly elevated temperatures. The MCOs will be sealed and transported via the transport cask to the Canister Storage Building.

The change of intracellular NAD level at the process of fusarium sambucinum growth and development

International Nuclear Information System (INIS)

Gulyamova, T.G.; Ehshtukhtarova, M.Kh.; Umarova, G.D.; Kerbalaeva, A.M.; Khalmuradov, A.G.

1996-01-01

Alterations of intracellular NAD(Nicotinamide-Adenine Dinucleotide) level have been studied in the process of growth and development of Fusanium sambucinum, selected earlier as a potential NAD producer. It was established that essential fluctuations of NAD concentration are dependent on growth phase, morphological cell type and DNA biosynthesis, that allowed to propose a real linkage between coenzyme pool and replicative activity of cells. (author). 7 refs., 2 figs

Hanford Quarter Seismic Report - 98C Seismicity On and Near the Hanford Site, Pasco Basin, Washington: April 1, 1998 Through June 30, 1998

Energy Technology Data Exchange (ETDEWEB)

DC Hartshorn, SP Reidel, AC Rohay

1998-10-23

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the U.S. Department of Energy and its contractors. The staff also locates aud identifies sources of seismic activity and monitors changes in the hi~orical pattern of seismic activity at the Hanford Site. The data are. compiled archived, and published for use by the Hanford Site for waste management Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of zin earthquake on the Hanford Site. The HSN and Ihe Eastern Washington Regional Network (EN/RN) consist-of 42 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The operational rate for the third quarter of FY 1998 for stations in the HSN was 99.99%. The operational rate for the third quarter of FY 1998 for stations of the EWRN was 99.95%. For the third quarter of FY 1998, the acquisition computer triggered 133 times. Of these triggers 11 were local earthquakes: 5 (45Yo) in the Columbia River Basalt Group, 2(1 8%) in the pre-basalt sediments, and 4 (36%) in the crystalline basement. The geologic and tectonic environments where these earthquakes occurred are discussed in this report.

Dynamic single-cell NAD(P)H measurement reveals oscillatory metabolism throughout the E. coli cell division cycle.

Science.gov (United States)

Zhang, Zheng; Milias-Argeitis, Andreas; Heinemann, Matthias

2018-02-01

Recent work has shown that metabolism between individual bacterial cells in an otherwise isogenetic population can be different. To investigate such heterogeneity, experimental methods to zoom into the metabolism of individual cells are required. To this end, the autofluoresence of the redox cofactors NADH and NADPH offers great potential for single-cell dynamic NAD(P)H measurements. However, NAD(P)H excitation requires UV light, which can cause cell damage. In this work, we developed a method for time-lapse NAD(P)H imaging in single E. coli cells. Our method combines a setup with reduced background emission, UV-enhanced microscopy equipment and optimized exposure settings, overall generating acceptable NAD(P)H signals from single cells, with minimal negative effect on cell growth. Through different experiments, in which we perturb E. coli's redox metabolism, we demonstrated that the acquired fluorescence signal indeed corresponds to NAD(P)H. Using this new method, for the first time, we report that intracellular NAD(P)H levels oscillate along the bacterial cell division cycle. The developed method for dynamic measurement of NAD(P)H in single bacterial cells will be an important tool to zoom into metabolism of individual cells.

Hanford Site Environmental Report for Calendar Year 2002

Energy Technology Data Exchange (ETDEWEB)

Poston, Ted M.; Hanf, Robert W.; Dirkes, Roger L.; Morasch, Launa F.

2003-09-01

This report is prepared annually to satisfy the requirements of DOE Orders. The report provides an overview of activities at the Hanford Site during 2002 and demonstrates the site's compliance with applicable federal, state, and local environmental laws, regulations, executive orders, and DOE policies; and to summarize environmental data that characterize Hanford Site environmental management performance. The purpose of the report is to provide useful summary information to members of the public, public officials, regulators, Hanford contractors, and elected representatives.

Regulatory Closure Options for the Residue in the Hanford Site Single-Shell Tanks

Energy Technology Data Exchange (ETDEWEB)

Cochran, J.R. Shyr, L.J.

1998-10-05

Liquid, mixed, high-level radioactive waste (HLW) has been stored in 149 single-shell tanks (SSTS) located in tank farms on the U.S. Department of Energy's (DOE's) Hanford Site. The DOE is developing technologies to retrieve as much remaining HLW as technically possible prior to physically closing the tank farms. In support of the Hanford Tanks Initiative, Sandia National Laboratories has addressed the requirements for the regulatory closure of the radioactive component of any SST residue that may remain after physical closure. There is significant uncertainty about the end state of each of the 149 SSTS; that is, the nature and amount of wastes remaining in the SSTS after retrieval is uncertain. As a means of proceeding in the face of these uncertainties, this report links possible end-states with associated closure options. Requirements for disposal of HLW and low-level radioactive waste (LLW) are reviewed in detail. Incidental waste, which is radioactive waste produced incidental to the further processing of HLW, is then discussed. If the low activity waste (LAW) fraction from the further processing of HLW is determined to be incidental waste, then DOE can dispose of that incidental waste onsite without a license from the U.S. Nuclear Regulatory Commissions (NRC). The NRC has proposed three Incidental Waste Criteria for determining if a LAW fraction is incidental waste. One of the three Criteria is that the LAW fraction should not exceed the NRC's Class C limits.

Regulatory Closure Options for the Residue in the Hanford Site Single-Shell Tanks

International Nuclear Information System (INIS)

Cochran, J.R.; Shyr, L.J.

1998-01-01

Liquid, mixed, high-level radioactive waste (HLW) has been stored in 149 single-shell tanks (SSTS) located in tank farms on the U.S. Department of Energy's (DOE's) Hanford Site. The DOE is developing technologies to retrieve as much remaining HLW as technically possible prior to physically closing the tank farms. In support of the Hanford Tanks Initiative, Sandia National Laboratories has addressed the requirements for the regulatory closure of the radioactive component of any SST residue that may remain after physical closure. There is significant uncertainty about the end state of each of the 149 SSTS; that is, the nature and amount of wastes remaining in the SSTS after retrieval is uncertain. As a means of proceeding in the face of these uncertainties, this report links possible end-states with associated closure options. Requirements for disposal of HLW and low-level radioactive waste (LLW) are reviewed in detail. Incidental waste, which is radioactive waste produced incidental to the further processing of HLW, is then discussed. If the low activity waste (LAW) fraction from the further processing of HLW is determined to be incidental waste, then DOE can dispose of that incidental waste onsite without a license from the U.S. Nuclear Regulatory Commissions (NRC). The NRC has proposed three Incidental Waste Criteria for determining if a LAW fraction is incidental waste. One of the three Criteria is that the LAW fraction should not exceed the NRC's Class C limits

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

International Nuclear Information System (INIS)

Rathbone, Bruce A.

2007-01-01

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at Hanford. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with 10 CFR 835, DOELAP, DOE-RL, ORP, PNSO, and Hanford contractor requirements. The dosimetry system is operated by PNNL's Hanford External Dosimetry Program (HEDP) which provides dosimetry services to all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee (HPDAC) which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. Rev. 0 marks the first revision to be released through PNNL's Electronic Records and Information Capture Architecture (ERICA) database. Revision numbers that are whole numbers reflect major revisions typically involving changes to all chapters in the document. Revision numbers that include a decimal fraction reflect minor revisions, usually restricted to selected chapters or selected pages in the document. Revision Log: Rev. 0 (2/25/2005) Major revision and expansion. Rev. 0.1 (3/12/2007) Minor

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

Energy Technology Data Exchange (ETDEWEB)

Rathbone, Bruce A.

2007-03-12

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at Hanford. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with 10 CFR 835, DOELAP, DOE-RL, ORP, PNSO, and Hanford contractor requirements. The dosimetry system is operated by PNNL’s Hanford External Dosimetry Program (HEDP) which provides dosimetry services to all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee (HPDAC) which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. Rev. 0 marks the first revision to be released through PNNL’s Electronic Records & Information Capture Architecture (ERICA) database. Revision numbers that are whole numbers reflect major revisions typically involving changes to all chapters in the document. Revision numbers that include a decimal fraction reflect minor revisions, usually restricted to selected chapters or selected pages in the document. Revision Log: Rev. 0 (2/25/2005) Major revision and expansion. Rev. 0.1 (3/12/2007) Minor

Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae

NARCIS (Netherlands)

Al-Saryi, Nadal A.; Al-Hejjaj, Murtakab Y.; van Roermund, Carlo W. T.; Hulmes, Georgia E.; Ekal, Lakhan; Payton, Chantell; Wanders, Ronald J. A.; Hettema, Ewald H.

2017-01-01

In Saccharomyces cerevisiae, peroxisomes are the sole site of fatty acid beta-oxidation. During this process, NAD(+) is reduced to NADH. When cells are grown on oleate medium, peroxisomal NADH is reoxidised to NAD(+) by malate dehydrogenase (Mdh3p) and reduction equivalents are transferred to the

Ground-water contribution to dose from past Hanford Operations

International Nuclear Information System (INIS)

Freshley, M.D.; Thorne, P.D.

1992-08-01

The Hanford Environmental Dose Reconstruction (HEDR) Project is being conducted to estimate radiation doses that populations and individuals could have received from Hanford Site operations from 1944 to the present. Four possible pathways by which radionuclides migrating in ground water on the Hanford Site could have reached the public have been identified: (1) through contaminated ground water migrating to the Columbia River; (2) through wells on or adjacent to the Hanford Site; (3) through wells next to the Columbia River downstream of Hanford that draw some or all of their water from the river (riparian wells); and (4) through atmospheric deposition resulting in contamination of a small watershed that, in turn, results in contamination of a shallow well or spring by transport in the ground water. These four pathways make up the ''ground-water pathway,'' which is the subject of this study. Assessment of the ground-water pathway was performed by (1) reviewing the existing extensive literature on ground water and ground-water monitoring at Hanford and (2) performing calculations to estimate radionuclide concentrations where no monitoring data were collected. Radiation doses that would result from exposure to these radionuclides were calculated

Hanford Site National Environmental Policy Act (NEPA) Characterization

Energy Technology Data Exchange (ETDEWEB)

Cushing, C.E. (ed.)

1992-12-01

This fifth revision of the Hanford Site National Environmental Policy (NEPA) Characterization presents current environmental data regarding the Hanford Site and its immediate environs. This information is intended for use in preparing Site-related NEPA documentation. Information is presented on climate and meteorology, geology and hydrology, ecology, history and archaeology, socioeconomics, land use, and noise levels, prepared by Pacific Northwest Laboratory (PNL) staff. Models are described that are to be used in simulating realized or potential impacts from nuclear materials at the Hanford Site. Included are models of radionuclide transport in groundwater and atmospheric pathways, and of radiation dose to populations via all known pathways from known initial conditions. Federal and state regulations, DOE orders and permits, and environmental standards directly applicable for the NEPA documents at the Hanford Site, are provided.

Hanford Site National Environmental Policy Act (NEPA) Characterization

International Nuclear Information System (INIS)

Cushing, C.E.

1992-12-01

This fifth revision of the Hanford Site National Environmental Policy (NEPA) Characterization presents current environmental data regarding the Hanford Site and its immediate environs. This information is intended for use in preparing Site-related NEPA documentation. Information is presented on climate and meteorology, geology and hydrology, ecology, history and archaeology, socioeconomics, land use, and noise levels, prepared by Pacific Northwest Laboratory (PNL) staff. Models are described that are to be used in simulating realized or potential impacts from nuclear materials at the Hanford Site. Included are models of radionuclide transport in groundwater and atmospheric pathways, and of radiation dose to populations via all known pathways from known initial conditions. Federal and state regulations, DOE orders and permits, and environmental standards directly applicable for the NEPA documents at the Hanford Site, are provided

Mutations that Allow SIR2 Orthologs to Function in a NAD+-Depleted Environment.

Science.gov (United States)

Ondracek, Caitlin R; Frappier, Vincent; Ringel, Alison E; Wolberger, Cynthia; Guarente, Leonard

2017-03-07

Sirtuin enzymes depend on NAD + to catalyze protein deacetylation. Therefore, the lowering of NAD + during aging leads to decreased sirtuin activity and may speed up aging processes in laboratory animals and humans. In this study, we used a genetic screen to identify two mutations in the catalytic domain of yeast Sir2 that allow the enzyme to function in an NAD + -depleted environment. These mutant enzymes give rise to a significant increase of yeast replicative lifespan and increase deacetylation by the Sir2 ortholog, SIRT1, in mammalian cells. Our data suggest that these mutations increase the stability of the conserved catalytic sirtuin domain, thereby increasing the catalytic efficiency of the mutant enzymes. Our approach to identifying sirtuin mutants that permit function in NAD + -limited environments may inform the design of small molecules that can maintain sirtuin activity in aging organisms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Radioactive waste management at the Hanford Reservation

International Nuclear Information System (INIS)

Anon.

1979-01-01

During some 30 years of plutonium production, the Hanford Reservation has accumulated large quantities of low- and high-level radioactive wastes. The high-level wastes have been stored in underground tanks, and the low-level wastes have been percolated into the soil. In recent years some programs for solidification and separation of the high-level wastes have been initiated. The Hanford waste-management system was studied by a panel of the Committee on Radioactive Waste Management of the National Academy of Sciences. The panel concluded that Hanford waste-management practices were adequate at present and for the immediate future but recommended increased research and development programs related to long-term isolation of the wastes. The panel also considered some alternatives for on-site disposal of the wastes. The Hanford Reservation was originally established for the production of plutonium for military purposes. During more than 30 years of operation, large volumes of high- and low-level radioactive wastes have been accumulated and contained at the site. The Management of these wastes has been the subject of controversy and criticism. To obtain a true technical evaluation of the Hanford waste situation, the Energy Research and Development Administration (now part of the Department of Energy) issued a contract to the National Academy of Sciences and the National Research Councilto conduct an independent review and evaluation of the Hanford waste-management practices and plans. A panel of the Committee on Radioactive Waste Management (CRWM) of the National Academy of Sciences conducted this study between the summer of 1976 and the summer of 1977. This article is a summary of the final report of that panel

Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD Concentration in Human Primary Astrocytes

Directory of Open Access Journals (Sweden)

Ross Grant

2010-01-01

Full Text Available Efficient synthesis of NAD + is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s by which cells of the central nervous system produce NAD + . The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP and de novo NAD + synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD + levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD + levels after 24 hrs. This decrease in NAD + was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide.

Kynurenine Pathway Metabolism is Involved in the Maintenance of the Intracellular NAD+ Concentration in Human Primary Astrocytes

Science.gov (United States)

Grant, Ross; Nguyen, Susan; Guillemin, Gilles

2010-01-01

Efficient synthesis of NAD+ is critical to maintaining cell viability in all organs of the body. However, little is known of the pathway(s) by which cells of the central nervous system produce NAD+. The aim of this study was to investigate the relationship, between tryptophan degradation via the kynurenine pathway (KP) and de novo NAD+ synthesis in human astrocytes, a major cell type within the brain. In this study we observed that inhibition of single enzymes of the KP resulted in significant decreases in NAD+ levels in astroglial cells after a 24 hr period. We also observed that astrocytes cultured in media deficient in tryptophan, nicotinic acid and nicotinamide resulted in a 50% decrease in NAD+ levels after 24 hrs. This decrease in NAD+ was partially restored by supplementation of the culture media with either tryptophan or kynurenine, or nicotinic acid or with supply of the salvage pathway precursor nicotinamide. PMID:22084595

Hanford annual first quarter seismic report, fiscal year 1998: Seismicity on and near the Hanford Site, Pasco Basin, Washington

Energy Technology Data Exchange (ETDEWEB)

Hartshorn, D.C.; Reidel, S.P.; Rohay, A.C.

1998-02-01

Hanford Seismic Monitoring provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network (HSN) for the US Department of Energy and its contractors. The staff also locates and identifies sources of seismic activity and monitors changes in the historical pattern of seismic activity at the hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, Natural Phenomena Hazards assessments, and engineering design and construction. In addition, the seismic monitoring organization works with the Hanford Site Emergency Services Organization to provide assistance in the event of an earthquake on the Hanford Site. The HSN and the Eastern Washington Regional Network (EWRN) consist of 41 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Monitoring staff. The operational rate for the first quarter of FY98 for stations in the HSN was 98.5%. The operational rate for the first quarter of FY98 for stations of the EWRN was 99.1%. For the first quarter of FY98, the acquisition computer triggered 184 times. Of these triggers 23 were local earthquakes: 7 in the Columbia River Basalt Group, and 16 in the crystalline basement. The geologic and tectonic environments where these earthquakes occurred are discussed in this report. The most significant earthquakes in this quarter were a series of six events which occurred in the Cold Creek depression (approximately 4 km SW of the 200 West Area), between November 6 and November 11, 1997. All events were deep (> 15 km) and were located in the crystalline basement. The first event was the largest, having a magnitude of 3.49 M{sub c}. Two events on November 9, 1997 had magnitudes of 2.81 and 2.95 M{sub c}, respectively. The other events had magnitudes between 0.7 and 1.2 M{sub c}.

Third Quarter Hanford Seismic Report for Fiscal Year 2009

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2009-09-30

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The HSAP is responsible for locating and identifying sources of seismic activity and monitoring changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the HSAP works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. The Hanford Seismic Network recorded 771 local earthquakes during the third quarter of FY 2009. Nearly all of these earthquakes were detected in the vicinity of Wooded Island, located about eight miles north of Richland just west of the Columbia River. The Wooded Island events recorded this quarter is a continuation of the swarm events observed during the January – March 2009 time period and reported in the previous quarterly report (Rohay et al, 2009). The frequency of Wooded Island events has subsided with 16 events recorded during June 2009. Most of the events were considered minor (magnitude (Mc) less than 1.0) with 25 events in the 2.0-3.0 range. The estimated depths of the Wooded Island events are shallow (averaging less than 1.0 km deep) with a maximum depth estimated at 2.2 km. This places the Wooded Island events within the Columbia River Basalt Group (CRBG). The low magnitude of the Wooded Island events has made them undetectable to all but local area residents. However, some Hanford employees working within a few miles of the area of highest activity

Annual Hanford Seismic Report for Fiscal Year 2009

Energy Technology Data Exchange (ETDEWEB)

Rohay, Alan C.; Sweeney, Mark D.; Hartshorn, Donald C.; Clayton, Ray E.; Devary, Joseph L.

2009-12-31

The Hanford Seismic Assessment Program (HSAP) provides an uninterrupted collection of high-quality raw and processed seismic data from the Hanford Seismic Network for the U.S. Department of Energy and its contractors. The HSAP is responsible for locating and identifying sources of seismic activity and monitoring changes in the historical pattern of seismic activity at the Hanford Site. The data are compiled, archived, and published for use by the Hanford Site for waste management, natural phenomena hazards assessments, and engineering design and construction. In addition, the HSAP works with the Hanford Site Emergency Services Organization to provide assistance in the event of a significant earthquake on the Hanford Site. The Hanford Seismic Network and the Eastern Washington Regional Network consist of 44 individual sensor sites and 15 radio relay sites maintained by the Hanford Seismic Assessment Team. During FY 2009, the Hanford Seismic Network recorded nearly 3000 triggers on the seismometer system, which included over 1700 seismic events in the southeast Washington area and an additional 370 regional and teleseismic events. There were 1648 events determined to be local earthquakes relevant to the Hanford Site. Nearly all of these earthquakes were detected in the vicinity of Wooded Island, located about eight miles north of Richland just west of the Columbia River. Recording of the Wooded Island events began in January with over 250 events per month through June 2009. The frequency of events decreased starting in July 2009 to approximately 10-15 events per month through September 2009. Most of the events were considered minor (coda-length magnitude [Mc] less than 1.0) with 47 events in the 2.0-3.0 range. The estimated depths of the Wooded Island events are shallow (averaging less than 1.0 km deep) with a maximum depth estimated at 2.3 km. This places the Wooded Island events within the Columbia River Basalt Group (CRBG). The highest-magnitude event (3.0Mc

Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

Science.gov (United States)

Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

2016-11-01

Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH

DEFF Research Database (Denmark)

Madsen, Andreas Stahl; Andersen, Christian; Daoud, Mohammad Mahdi

2016-01-01

Protein lysine posttranslational modification by an increasing number of different acyl groups is becoming appreciated as a regulatory mechanism in cellular biology. Sirtuins are class III histone deacylases that use NAD+ as a co-substrate during amide bond hydrolysis. Several studies have...... described the sirtuins as sensors of the NAD+/NADH ratio, but it has not been formally tested for all the mammalian sirtuins in vitro. To address this problem, we first synthesized a wide variety of peptide-based probes, which were used to identify the range of hydrolytic activities of human sirtuins...... to be prone to hydrolytic cleavage by SIRT1-3 and SIRT6, supporting recent findings. We then tested the ability of NADH, ADP-ribose, and nicotinamide to inhibit these NAD+-dependent deacylase activities of the sirtuins. In the commonly used 7-amino-4-methylcoumarin-coupled fluorescence-based assay...

Design criteria for the light duty utility arm system end effectors

International Nuclear Information System (INIS)

Pardini, A.F.

1995-01-01

This document provides the criteria for the design of end effectors that will be used as part of the Light Duty Utility Arm (LDUA) System. The LDUA System consists of a deployment vehicle, a vertical positioning mast, a light duty multi-axis robotic arm, a tank riser interface and confinement, a tool interface plate, a control system, and an operations control trailer. The criteria specified in this document will apply to all end effector systems being developed for use on or with the LDUA system at the Hanford site. The requirement stipulated in this document are mandatory

Overview of the Hanford risk management plan

International Nuclear Information System (INIS)

Halverson, T.G.

1998-01-01

The Project Hanford Management Contract called for the enhancement of site-wide decision processes, and development of a Hanford Risk Management Plan to adopt or develop a risk management system for the Hanford Site. This Plan provides a consistent foundation for Site issues and addresses site-wide management of risks of all types. It supports the Department of Energy planning and sitewide decision making policy. Added to this requirement is a risk performance report to characterize the risk management accomplishments. This paper presents the development of risk management within the context of work planning and performance. Also discussed are four risk elements which add value to the context

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

Energy Technology Data Exchange (ETDEWEB)

Rathbone, Bruce A.

2010-04-01

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at the U.S. Department of Energy (DOE) Hanford site. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with requirements of 10 CFR 835, the DOE Laboratory Accreditation Program, the DOE Richland Operations Office, DOE Office of River Protection, DOE Pacific Northwest Office of Science, and Hanford’s DOE contractors. The dosimetry system is operated by the Pacific Northwest National Laboratory (PNNL) Hanford External Dosimetry Program which provides dosimetry services to PNNL and all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since its inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. The first revision to be released through PNNL’s Electronic Records & Information Capture Architecture database was designated Revision 0. Revision numbers that are whole numbers reflect major revisions typically involving significant changes to all chapters in the document. Revision

Hanford External Dosimetry Technical Basis Manual PNL-MA-842

Energy Technology Data Exchange (ETDEWEB)

Rathbone, Bruce A.

2011-04-04

The Hanford External Dosimetry Technical Basis Manual PNL-MA-842 documents the design and implementation of the external dosimetry system used at the U.S. Department of Energy (DOE) Hanford site. The manual describes the dosimeter design, processing protocols, dose calculation methodology, radiation fields encountered, dosimeter response characteristics, limitations of dosimeter design under field conditions, and makes recommendations for effective use of the dosimeters in the field. The manual describes the technical basis for the dosimetry system in a manner intended to help ensure defensibility of the dose of record at Hanford and to demonstrate compliance with requirements of 10 CFR 835, the DOE Laboratory Accreditation Program, the DOE Richland Operations Office, DOE Office of River Protection, DOE Pacific Northwest Office of Science, and Hanford’s DOE contractors. The dosimetry system is operated by the Pacific Northwest National Laboratory (PNNL) Hanford External Dosimetry Program which provides dosimetry services to PNNL and all Hanford contractors. The primary users of this manual are DOE and DOE contractors at Hanford using the dosimetry services of PNNL. Development and maintenance of this manual is funded directly by DOE and DOE contractors. Its contents have been reviewed and approved by DOE and DOE contractors at Hanford through the Hanford Personnel Dosimetry Advisory Committee which is chartered and chaired by DOE-RL and serves as means of coordinating dosimetry practices across contractors at Hanford. This manual was established in 1996. Since its inception, it has been revised many times and maintained by PNNL as a controlled document with controlled distribution. The first revision to be released through PNNL’s Electronic Records & Information Capture Architecture database was designated Revision 0. Revision numbers that are whole numbers reflect major revisions typically involving significant changes to all chapters in the document. Revision

Hanford Central Waste Complex: Waste Receiving and Processing Facility dangerous waste permit application

International Nuclear Information System (INIS)

1991-10-01

The Hanford Central Waste Complex is an existing and planned series of treatment, and/or disposal (TSD) unites that will centralize the management of solid waste operations at a single location on the Hanford Facility. The Complex includes two units: the WRAP Facility and the Radioactive Mixed Wastes Storage Facility (RMW Storage Facility). This Part B permit application addresses the WRAP Facility. The Facility will be a treatment and storage unit that will provide the capability to examine, sample, characterize, treat, repackage, store, and certify radioactive and/or mixed waste. Waste treated and stored will include both radioactive and/or mixed waste received from onsite and offsite sources. Certification will be designed to ensure and demonstrate compliance with waste acceptance criteria set forth by onsite disposal units and/or offsite facilities that subsequently are to receive waste from the WRAP Facility. This permit application discusses the following: facility description and general provisions; waste characterization; process information; groundwater monitoring; procedures to prevent hazards; contingency plant; personnel training; exposure information report; waste minimization plan; closure and postclosure requirements; reporting and recordkeeping; other relevant laws; certification

Generation, Release, and Uptake of the NAD Precursor Nicotinic Acid Riboside by Human Cells.

Science.gov (United States)

Kulikova, Veronika; Shabalin, Konstantin; Nerinovski, Kirill; Dölle, Christian; Niere, Marc; Yakimov, Alexander; Redpath, Philip; Khodorkovskiy, Mikhail; Migaud, Marie E; Ziegler, Mathias; Nikiforov, Andrey

2015-11-06

NAD is essential for cellular metabolism and has a key role in various signaling pathways in human cells. To ensure proper control of vital reactions, NAD must be permanently resynthesized. Nicotinamide and nicotinic acid as well as nicotinamide riboside (NR) and nicotinic acid riboside (NAR) are the major precursors for NAD biosynthesis in humans. In this study, we explored whether the ribosides NR and NAR can be generated in human cells. We demonstrate that purified, recombinant human cytosolic 5'-nucleotidases (5'-NTs) CN-II and CN-III, but not CN-IA, can dephosphorylate the mononucleotides nicotinamide mononucleotide and nicotinic acid mononucleotide (NAMN) and thus catalyze NR and NAR formation in vitro. Similar to their counterpart from yeast, Sdt1, the human 5'-NTs require high (millimolar) concentrations of nicotinamide mononucleotide or NAMN for efficient catalysis. Overexpression of FLAG-tagged CN-II and CN-III in HEK293 and HepG2 cells resulted in the formation and release of NAR. However, NAR accumulation in the culture medium of these cells was only detectable under conditions that led to increased NAMN production from nicotinic acid. The amount of NAR released from cells engineered for increased NAMN production was sufficient to maintain viability of surrounding cells unable to use any other NAD precursor. Moreover, we found that untransfected HeLa cells produce and release sufficient amounts of NAR and NR under normal culture conditions. Collectively, our results indicate that cytosolic 5'-NTs participate in the conversion of NAD precursors and establish NR and NAR as integral constituents of human NAD metabolism. In addition, they point to the possibility that different cell types might facilitate each other's NAD supply by providing alternative precursors. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.