NUCLEAR MATERIAL ATTRACTIVENESS: AN ASSESSMENT OF MATERIAL ASSOCIATED WITH A CLOSED FUEL CYCLE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bathke, C. G.; Ebbinghaus, B.; Sleaford, Brad W.

2010-06-11

This paper examines the attractiveness of materials mixtures containing special nuclear materials (SNM) associated with the various processing steps required for a closed fuel cycle. This paper combines the results from earlier studies that examined the attractiveness of SNM associated with the processing of spent light water reactor (LWR) fuel by various reprocessing schemes and the recycle of plutonium as a mixed oxide (MOX) fuel in LWR with new results for the final, repeated burning of SNM in fast-spectrum reactors: fast reactors and accelerator driven systems (ADS). The results of this paper suggest that all reprocessing products evaluated so farmore » need to be rigorously safeguarded and provided moderate to high levels of physical protection. These studies were performed at the request of the United States Department of Energy (DOE), and are based on the calculation of "attractiveness levels" that has been couched in terms chosen for consistency with those normally used for nuclear materials in DOE nuclear facilities. The methodology and key findings will be presented. Additionally, how these attractiveness levels relate to proliferation resistance (e.g. by increasing impediments to the diversion, theft, or undeclared production of SNM for the purpose of acquiring a nuclear weapon), and how they could be used to help inform policy makers, will be discussed.« less

FURTHER ASSESSMENTS OF THE ATTRACTIVENESS OF MATERIALS IN ADVANCED NUCLEAR FUEL CYCLES FROM A SAFEGUARDS PERSPECTIVE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bathke, C. G.; Jarvinen, G. D.; Wallace, R. K.

2008-10-01

This paper summarizes the results of an extension to an earlier study [ ] that examined the attractiveness of materials mixtures containing special nuclear materials (SNM) associated with the PUREX, UREX+, and COEX reprocessing schemes. This study focuses on the materials associated with the UREX, COEX, THOREX, and PYROX reprocessing schemes. This study also examines what is required to render plutonium as “unattractive.” Furthermore, combining the results of this study with those from the earlier study permits a comparison of the uranium and thorium based fuel cycles on the basis of the attractiveness of the SNM associated with each fuelmore » cycle. Both studies were performed at the request of the United States Department of Energy (DOE), and are based on the calculation of “attractiveness levels” that has been couched in terms chosen for consistency with those normally used for nuclear materials in DOE nuclear facilities [ ]. The methodology and key findings will be presented. Additionally, how these attractiveness levels relate to proliferation resistance (e.g. by increasing impediments to the diversion, theft, undeclared production of SNM for the purpose of acquiring a nuclear weapon), and how they could be used to help inform policy makers, will be discussed.« less

Quantification of 235U and 238U activity concentrations for undeclared nuclear materials by a digital gamma-gamma coincidence spectroscopy.

PubMed

Zhang, Weihua; Yi, Jing; Mekarski, Pawel; Ungar, Kurt; Hauck, Barry; Kramer, Gary H

2011-06-01

The purpose of this study is to investigate the possibility of verifying depleted uranium (DU), natural uranium (NU), low enriched uranium (LEU) and high enriched uranium (HEU) by a developed digital gamma-gamma coincidence spectroscopy. The spectroscopy consists of two NaI(Tl) scintillators and XIA LLC Digital Gamma Finder (DGF)/Pixie-4 software and card package. The results demonstrate that the spectroscopy provides an effective method of (235)U and (238)U quantification based on the count rate of their gamma-gamma coincidence counting signatures. The main advantages of this approach over the conventional gamma spectrometry include the facts of low background continuum near coincident signatures of (235)U and (238)U, less interference from other radionuclides by the gamma-gamma coincidence counting, and region-of-interest (ROI) imagine analysis for uranium enrichment determination. Compared to conventional gamma spectrometry, the method offers additional advantage of requiring minimal calibrations for (235)U and (238)U quantification at different sample geometries. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Exploratory field trial of motorcycle autonomous emergency braking (MAEB): Considerations on the acceptability of unexpected automatic decelerations.

PubMed

Savino, Giovanni; Pierini, Marco; Thompson, Jason; Fitzharris, Michael; Lenné, Michael G

2016-11-16

Autonomous emergency braking (AEB) acts to slow down a vehicle when an unavoidable impending collision is detected. In addition to documented benefits when applied to passenger cars, AEB has also shown potential when applied to motorcycles (MAEB). However, the feasibility of MAEB as practically applied to motorcycles in the real world is not well understood. In this study we performed a field trial involving 16 riders on a test motorcycle subjected to automatic decelerations, thus simulating MAEB activation. The tests were conducted along a rectilinear path at nominal speed of 40 km/h and with mean deceleration of 0.15 g (15% of full braking) deployed at random times. Riders were also exposed to one final undeclared brake activation with the aim of providing genuinely unexpected automatic braking events. Participants were consistently able to manage automatic decelerations of the vehicle with minor to moderate effort. Results of undeclared activations were consistent with those of standard runs. This study demonstrated the feasibility of a moderate automatic deceleration in a scenario of motorcycle travelling in a straight path, supporting the notion that the application of AEB on motorcycles is practicable. Furthermore, the proposed field trial can be used as a reference for future regulation or consumer tests in order to address safety and acceptability of unexpected automatic decelerations on a motorcycle.

A Limited Survey of Dark Chocolate Bars Obtained in the United States for Undeclared Milk and Peanut Allergens.

PubMed

Bedford, Binaifer; Yu, Ye; Wang, Xue; Garber, Eric A E; Jackson, Lauren S

2017-04-01

Undeclared allergens in chocolate products have been responsible for numerous allergen-related recalls in the United States. A survey was conducted to determine the prevalence of undeclared milk and peanut in 88 and 78 dark chocolate bars, respectively. Concentrations of milk (as nonfat dry milk) or peanut in three samples of each chocolate product were determined with two milk- or peanut-specific enzyme-linked immunosorbent assay kits. In 75% of the chocolate bar products with a milk advisory statement, milk concentrations were above the limit of quantitation (2.5 μg/g [ppm]), with the majority having concentrations >1,000 ppm. An additional 67% of chocolate bars with a "traces of milk" statement contained 3 to 6,700 ppm of milk. Fifteen percent of chocolates labeled dairy free or lactose free and 25% labeled vegan were positive for milk, all with concentrations >1,000 ppm. Even for chocolates with no reference to milk on the label, 33% of these products contained 60 to 3,400 ppm of milk. The survey of chocolate products for peanuts revealed that 8% of products with an advisory statement contained peanut, with the highest concentration of 550 ppm. All nine chocolates bearing the peanut-free or allergen-free statement were negative for peanut, but 17% of chocolates with no label statement for peanut were positive for peanut at concentrations of 9 to 170 ppm. Evaluation of multiple lots of four chocolate products revealed that milk was consistently present or absent for the products investigated, but mixed results were obtained when multiple lots were tested for peanut. This study indicates that a large proportion of dark chocolate bars contain undeclared milk. The type of advisory statement or the absence of a milk advisory statement on products did not predict the amount or absence of milk protein. In contrast, a lower proportion of chocolates containing undeclared peanut was found. Consumers with food allergies should be cautious when purchasing dark chocolate products, particularly those that have an advisory label statement.

DN/DG Screening of Environmental Swipe Samples: FY2016 Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glasgow, David C.; Croft, Stephen; Venkataraman, Ramkumar

The Delayed Neutron Delayed Gamma (DNDG) technique provides a new analytical capability to the International Atomic Energy Agency (IAEA) for detecting undeclared nuclear activities. IAEA’s Long Term R&D (LTRD) plan has a stated high urgency need to develop elemental and isotopic signatures of nuclear fuel cycle activities and processes (LTRD 2.2). The new DNDG capability is used to co-detect both uranium and plutonium as an extension of a DN only method that is already being utilized by the IAEA for the analysis of swipes to inform on undeclared nuclear activities. Analytical method involving irradiation of swipe samples potentially containing tracemore » quantities of fissile material in a thermal neutron field, followed by the counting of delayed neutrons, is a well-known technique in the field of safeguards and nonproliferation. It is used for detecting the presence of microscopic amounts of fissile material, (typically a linear combination of 233U, 235U, 239Pu, and 241Pu)and quantifying it in terms of the equivalent mass of 235U. The delayed neutron (DN) technique is very sensitive and is been routinely employed at the High Flux Isotope Reactor (HFIR) facility at Oak Ridge National Laboratory (ORNL). Both uranium and plutonium are of high safeguards value. However, the DN technique is not well suited for distinguishing between U and Pu isotopes since the decay curves overlap closely. The delayed gamma (DG) technique will help detect the presence of 239Pu in a mixture of U and Pu. Thus the DNDG approach combines the best of both worlds; the sensitivity of DN counting and the isotopic specificity of DG counting. The present work seeks to build on the delayed neutron and delayed gamma methods that have been developed at ORNL. It is recognized that the distribution profile of heavy fission products remains fairly invariant for the fissile nuclides whereas the distribution of light fission products varies from one isotope to another. That is, the ratio of the yield of a light fission fragment to a heavy fission fragments is isotope specific. Measurement of the ratio of the net full energy peak (FEP) from low/high mass fission products is an elegant way to characterize the fraction of fissile materials present in a mixture. By empirically calibrating the ratio of the net FEP as a function of known concentration of the binary mixture, one can determine the fraction of fissile isotopes in an unknown sample. In the work done in fiscal year (FY) 2016, samples of single fissile material isotopes as well as binary mixtures were irradiated in a well thermalized irradiation field in the HFIR. Delayed neutron counting was performed using the neutron counter at the HFIR Neutron Activation Analysis (NAA) laboratory. Delayed gamma counting was performed using a shielded high purity germanium (HPGe) detector. Delayed neutron decay curve results highlighted the difficulty of distinguishing between U and Pu isotopes, and the need for including the delayed gamma component. Based on delayed gamma spectrometry, twelve ratios of low mass/high fission product gamma ray FEP have been identified as valid candidates. Linearity of the ratios, as a function of 239Pu fraction in 235U+ 239Pu mixtures, was confirmed for the low mass/high mass candidates that were selected. The DNDG method we are spearheading allows not only the presence of total fissile content to be detected, but whether the material is predominantly U or predominantly Pu, or a mixture. This provides additional SG relevant information.« less

Minor isotope safeguards techniques (MIST): Analysis and visualization of gas centrifuge enrichment plant process data using the MSTAR model

NASA Astrophysics Data System (ADS)

Shephard, Adam M.; Thomas, Benjamin R.; Coble, Jamie B.; Wood, Houston G.

2018-05-01

This paper presents a development related to the use of minor isotope safeguards techniques (MIST) and the MSTAR cascade model as it relates to the application of international nuclear safeguards at gas centrifuge enrichment plants (GCEPs). The product of this paper is a derivation of the universal and dimensionless MSTAR cascade model. The new model can be used to calculate the minor uranium isotope concentrations in GCEP product and tails streams or to analyze, visualize, and interpret GCEP process data as part of MIST. Applications of the new model include the detection of undeclared feed and withdrawal streams at GCEPs when used in conjunction with UF6 sampling and/or other isotopic measurement techniques.

AGM2015: Antineutrino Global Map 2015

PubMed Central

Usman, S.M.; Jocher, G.R.; Dye, S.T.; McDonough, W.F.; Learned, J.G.

2015-01-01

Every second greater than 1025 antineutrinos radiate to space from Earth, shining like a faint antineutrino star. Underground antineutrino detectors have revealed the rapidly decaying fission products inside nuclear reactors, verified the long-lived radioactivity inside our planet, and informed sensitive experiments for probing fundamental physics. Mapping the anisotropic antineutrino flux and energy spectrum advance geoscience by defining the amount and distribution of radioactive power within Earth while critically evaluating competing compositional models of the planet. We present the Antineutrino Global Map 2015 (AGM2015), an experimentally informed model of Earth’s surface antineutrino flux over the 0 to 11 MeV energy spectrum, along with an assessment of systematic errors. The open source AGM2015 provides fundamental predictions for experiments, assists in strategic detector placement to determine neutrino mass hierarchy, and aids in identifying undeclared nuclear reactors. We use cosmochemically and seismologically informed models of the radiogenic lithosphere/mantle combined with the estimated antineutrino flux, as measured by KamLAND and Borexino, to determine the Earth’s total antineutrino luminosity at . We find a dominant flux of geo-neutrinos, predict sub-equal crust and mantle contributions, with ~1% of the total flux from man-made nuclear reactors. PMID:26323507

AGM2015: Antineutrino Global Map 2015.

PubMed

Usman, S M; Jocher, G R; Dye, S T; McDonough, W F; Learned, J G

2015-09-01

Every second greater than 10(25) antineutrinos radiate to space from Earth, shining like a faint antineutrino star. Underground antineutrino detectors have revealed the rapidly decaying fission products inside nuclear reactors, verified the long-lived radioactivity inside our planet, and informed sensitive experiments for probing fundamental physics. Mapping the anisotropic antineutrino flux and energy spectrum advance geoscience by defining the amount and distribution of radioactive power within Earth while critically evaluating competing compositional models of the planet. We present the Antineutrino Global Map 2015 (AGM2015), an experimentally informed model of Earth's surface antineutrino flux over the 0 to 11 MeV energy spectrum, along with an assessment of systematic errors. The open source AGM2015 provides fundamental predictions for experiments, assists in strategic detector placement to determine neutrino mass hierarchy, and aids in identifying undeclared nuclear reactors. We use cosmochemically and seismologically informed models of the radiogenic lithosphere/mantle combined with the estimated antineutrino flux, as measured by KamLAND and Borexino, to determine the Earth's total antineutrino luminosity at . We find a dominant flux of geo-neutrinos, predict sub-equal crust and mantle contributions, with ~1% of the total flux from man-made nuclear reactors.

Application of Reactor Antineutrinos: Neutrinos for Peace

NASA Astrophysics Data System (ADS)

Suekane, F.

2013-02-01

In nuclear reactors, 239Pu are produced along with burn-up of nuclear fuel. 239Pu is subject of safeguard controls since it is an explosive component of nuclear weapon. International Atomic Energy Agency (IAEA) is watching undeclared operation of reactors to prevent illegal production and removal of 239Pu. In operating reactors, a huge numbers of anti electron neutrinos (ν) are produced. Neutrino flux is approximately proportional to the operating power of reactor in short term and long term decrease of the neutrino flux per thermal power is proportional to the amount of 239Pu produced. Thus rector ν's carry direct and real time information useful for the safeguard purposes. Since ν can not be hidden, it could be an ideal medium to monitor the reactor operation. IAEA seeks for novel technologies which enhance their ability and reactor neutrino monitoring is listed as one of such candidates. Currently neutrino physicists are performing R&D of small reactor neutrino detectors to use specifically for the safeguard use in response to the IAEA interest. In this proceedings of the neutrino2012 conference, possibilities of such reactor neutrinos application and current world-wide R&D status are described.

Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM)

NASA Astrophysics Data System (ADS)

Coghlan, Megan L.; Maker, Garth; Crighton, Elly; Haile, James; Murray, Dáithí C.; White, Nicole E.; Byard, Roger W.; Bellgard, Matthew I.; Mullaney, Ian; Trengove, Robert; Allcock, Richard J. N.; Nash, Christine; Hoban, Claire; Jarrett, Kevin; Edwards, Ross; Musgrave, Ian F.; Bunce, Michael

2015-12-01

Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines.

Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM).

PubMed

Coghlan, Megan L; Maker, Garth; Crighton, Elly; Haile, James; Murray, Dáithí C; White, Nicole E; Byard, Roger W; Bellgard, Matthew I; Mullaney, Ian; Trengove, Robert; Allcock, Richard J N; Nash, Christine; Hoban, Claire; Jarrett, Kevin; Edwards, Ross; Musgrave, Ian F; Bunce, Michael

2015-12-10

Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines.

Combined DNA, toxicological and heavy metal analyses provides an auditing toolkit to improve pharmacovigilance of traditional Chinese medicine (TCM)

PubMed Central

Coghlan, Megan L.; Maker, Garth; Crighton, Elly; Haile, James; Murray, Dáithí C.; White, Nicole E.; Byard, Roger W.; Bellgard, Matthew I.; Mullaney, Ian; Trengove, Robert; Allcock, Richard J. N.; Nash, Christine; Hoban, Claire; Jarrett, Kevin; Edwards, Ross; Musgrave, Ian F.; Bunce, Michael

2015-01-01

Globally, there has been an increase in the use of herbal remedies including traditional Chinese medicine (TCM). There is a perception that products are natural, safe and effectively regulated, however, regulatory agencies are hampered by a lack of a toolkit to audit ingredient lists, adulterants and constituent active compounds. Here, for the first time, a multidisciplinary approach to assessing the molecular content of 26 TCMs is described. Next generation DNA sequencing is combined with toxicological and heavy metal screening by separation techniques and mass spectrometry (MS) to provide a comprehensive audit. Genetic analysis revealed that 50% of samples contained DNA of undeclared plant or animal taxa, including an endangered species of Panthera (snow leopard). In 50% of the TCMs, an undeclared pharmaceutical agent was detected including warfarin, dexamethasone, diclofenac, cyproheptadine and paracetamol. Mass spectrometry revealed heavy metals including arsenic, lead and cadmium, one with a level of arsenic >10 times the acceptable limit. The study showed 92% of the TCMs examined were found to have some form of contamination and/or substitution. This study demonstrates that a combination of molecular methodologies can provide an effective means by which to audit complementary and alternative medicines. PMID:26658160

Department of Energy Efforts to Promote Universal Adherence to the IAEA Additional Protocol

DOE Office of Scientific and Technical Information (OSTI.GOV)

Killinger, Mark H.; Hansen, Linda H.; Kovacic, Don N.

2009-10-06

Entry-into-force of the U.S. Additional Protocol (AP) in January 2009 continues to demonstrate the ongoing commitment by the United States to promote universal adherence to the AP. The AP is a critical tool for improving the International Atomic Energy Agency’s (IAEA) capabilities to detect undeclared activities that indicate a clandestine nuclear weapons program. This is because States Parties are required to provide information about, and access to, nuclear fuel cycle activities beyond their traditional safeguards reporting requirements. As part of the U.S. AP Implementation Act and Senate Resolution of Ratification, the Administration is required to report annually to Congress onmore » measures taken to achieve the adoption of the AP in non-nuclear weapon states, as well as assistance to the IAEA to promote the effective implementation of APs in those states. A key U.S. effort in this area is being managed by the International Nuclear Safeguards and Engagement Program (INSEP) of the U.S. Department of Energy (DOE). Through new and existing bilateral cooperation agreements, INSEP has initiated technical assistance projects for AP implementation with selected non-weapon states. States with which INSEP is currently cooperating include Vietnam and Thailand, with Indonesia, Algeria, Morocco, and other countries as possible future collaborators in the area of AP implementation. The INSEP collaborative model begins with a joint assessment with our partners to identify specific needs they may have regarding entering the AP into force and any impediments to successful implementation. An action plan is then developed detailing and prioritizing the necessary joint activities. Such assistance may include: advice on developing legal frameworks and regulatory documents; workshops to promote understanding of AP requirements; training to determine possible declarable activities; assistance in developing a system to collect and submit declarations; performing industry outreach to raise awareness; guidance for reporting export and manufacturing of “especially designed or prepared” equipment listed in AP Annex I/Annex II; and lastly, developing indigenous capabilities to sustain AP implementation. INSEP also coordinates with the IAEA to ensure the harmonization of the assistance provided by DOE and the IAEA. This paper describes current efforts and future plans for AP international implementation support.« less

Advances in the growth of alkaline-earth halide single crystals for scintillator detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boatner, Lynn A; Ramey, Joanne Oxendine; Kolopus, James A

2014-01-01

Alkaline-earth scintillators such as strontium iodide and other alkaline-earth halides activated with divalent europium represent some of the most efficient and highest energy resolution scintillators for use as gamma-ray detectors in a wide range of applications. These applications include the areas of nuclear nonproliferation, homeland security, the detection of undeclared nuclear material, nuclear physics and materials science, medical diagnostics, space physics, high energy physics, and radiation monitoring systems for first responders, police, and fire/rescue personnel. Recent advances in the growth of large single crystals of these scintillator materials hold the promise of higher crystal yields and significantly lower detector productionmore » costs. In the present work, we describe new processing protocols that, when combined with our molten salt filtration methods, have led to advances in achieving a significant reduction of cracking effects during the growth of single crystals of SrI2:Eu2+. In particular, we have found that extended pumping on the molten crystal-growth charge under vacuum for time periods extending up to 48 hours is generally beneficial in compensating for variations in the alkaline-earth halide purity and stoichiometry of the materials as initially supplied by commercial sources. These melt-pumping and processing techniques are now being applied to the purification of CaI2:Eu2+ and some mixed-anion europium-doped alkaline-earth halides prior to single-crystal growth by means of the vertical Bridgman technique. The results of initial studies of the effects of aliovalent doping of SrI2:Eu2+ on the scintillation characteristics of this material are also described.« less

Determination of caffeine and identification of undeclared substances in dietary supplements and caffeine dietary exposure assessment.

PubMed

Neves, Diana Brito da Justa; Caldas, Eloisa Dutra

2017-07-01

Caffeine is one of the most consumed stimulants in the world, and is a frequent ingredient of dietary supplements. The aims of this work were to validate a GC-MS method for the quantitation of caffeine and identification of other substances in supplements, mainly weight loss products, and to estimate the caffeine intake by consumers. Sample preparation included extraction with chloroform:water in ultrasonic bath, centrifugation and analysis of the organic layer for caffeine quantitation, and extraction with methanol for identification of other substances. A total of 213 samples of 52 supplement products not registered in Brazil and seized by the Brazilian Federal Police were analyzed. From the 109 samples that declared the amount of caffeine present, 26.6% contained more than 120% of the specified content. Considering the maximum recommended dose stated on the product labels, the consumption of 47.9% of the samples would lead to a daily intake of caffeine above the safe limit of 400 mg. Undeclared drugs, including sibutramine, phenolphthalein, amphepramone and femproporex were found in 28 samples. These results show that consumers of dietary supplements should be aware that these products might contain caffeine at levels that could represent potential health risks, in addition to undeclared pharmaceutical drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Use of open source information and commercial satellite imagery for nuclear nonproliferation regime compliance verification by a community of academics

NASA Astrophysics Data System (ADS)

Solodov, Alexander

The proliferation of nuclear weapons is a great threat to world peace and stability. The question of strengthening the nonproliferation regime has been open for a long period of time. In 1997 the International Atomic Energy Agency (IAEA) Board of Governors (BOG) adopted the Additional Safeguards Protocol. The purpose of the protocol is to enhance the IAEA's ability to detect undeclared production of fissile materials in member states. However, the IAEA does not always have sufficient human and financial resources to accomplish this task. Developed here is a concept for making use of human and technical resources available in academia that could be used to enhance the IAEA's mission. The objective of this research was to study the feasibility of an academic community using commercially or publicly available sources of information and products for the purpose of detecting covert facilities and activities intended for the unlawful acquisition of fissile materials or production of nuclear weapons. In this study, the availability and use of commercial satellite imagery systems, commercial computer codes for satellite imagery analysis, Comprehensive Test Ban Treaty (CTBT) verification International Monitoring System (IMS), publicly available information sources such as watchdog groups and press reports, and Customs Services information were explored. A system for integrating these data sources to form conclusions was also developed. The results proved that publicly and commercially available sources of information and data analysis can be a powerful tool in tracking violations in the international nuclear nonproliferation regime and a framework for implementing these tools in academic community was developed. As a result of this study a formation of an International Nonproliferation Monitoring Academic Community (INMAC) is proposed. This would be an independent organization consisting of academics (faculty, staff and students) from both nuclear weapon states (NWS) and non-nuclear weapon states (NNWS). This community analyzes all types of unclassified publicly and commercially available information to aid in detection of violations of the non-proliferation regime. INMAC shares all of this information with the IAEA and the public. Since INMAC is composed solely by members of the academic community, this organization would not demonstrate any biases in its investigations or reporting.

15 CFR 716.7 - Samples.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS INITIAL AND ROUTINE... will be restricted to verifying the absence of undeclared scheduled chemicals, unless otherwise agreed...

15 CFR 716.7 - Samples.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS INITIAL AND ROUTINE... will be restricted to verifying the absence of undeclared scheduled chemicals, unless otherwise agreed...

Great Cause—Small Effect: Undeclared Genetically Engineered Orange Petunias Harbor an Inefficient Dihydroflavonol 4-Reductase

PubMed Central

Haselmair-Gosch, Christian; Miosic, Silvija; Nitarska, Daria; Roth, Barbara L.; Walliser, Benjamin; Paltram, Renate; Lucaciu, Rares C.; Eidenberger, Lukas; Rattei, Thomas; Olbricht, Klaus; Stich, Karl; Halbwirth, Heidi

2018-01-01

A recall campaign for commercial, orange flowering petunia varieties in spring 2017 caused economic losses worldwide. The orange varieties were identified as undeclared genetically engineered (GE)-plants, harboring a maize dihydroflavonol 4-reductase (DFR, A1), which was used in former scientific transgenic breeding attempts to enable formation of orange pelargonidin derivatives from the precursor dihydrokaempferol (DHK) in petunia. How and when the A1 cDNA entered the commercial breeding process is unclear. We provide an in-depth analysis of three orange petunia varieties, released by breeders from three countries, with respect to their transgenic construct, transcriptomes, anthocyanin composition, and flavonoid metabolism at the level of selected enzymes and genes. The two possible sources of the A1 cDNA in the undeclared GE-petunia can be discriminated by PCR. A special version of the A1 gene, the A1 type 2 allele, is present, which includes, at the 3′-end, an additional 144 bp segment from the non-viral transposable Cin4-1 sequence, which does not add any functional advantage with respect to DFR activity. This unequivocally points at the first scientific GE-petunia from the 1980s as the A1 source, which is further underpinned e.g., by the presence of specific restriction sites, parts of the untranslated sequences, and the same arrangement of the building blocks of the transformation plasmid used. Surprisingly, however, the GE-petunia cannot be distinguished from native red and blue varieties by their ability to convert DHK in common in vitro enzyme assays, as DHK is an inadequate substrate for both the petunia and maize DFR. Recombinant maize DFR underpins the low DHK acceptance, and, thus, the strikingly limited suitability of the A1 protein for a transgenic approach for breeding pelargonidin-based flower color. The effect of single amino acid mutations on the substrate specificity of DFRs is demonstrated. Expression of the A1 gene is generally lower than the petunia DFR expression despite being under the control of the strong, constitutive p35S promoter. We show that a rare constellation in flavonoid metabolism—absence or strongly reduced activity of both flavonol synthase and B-ring hydroxylating enzymes—allows pelargonidin formation in the presence of DFRs with poor DHK acceptance. PMID:29541079

The evolution of information-driven safeguards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budlong-sylvester, Kory W; Pilat, Joseph F

2010-10-14

From the adoption of the Model Additional Protocol and integrated safeguards in the 1990s, to current International Atomic Energy Agency (IAEA) efforts to deal with cases of noncompliance, the question of how the Agency can best utilize all the information available to it remains of great interest and increasing importance. How might the concept of 'information-driven' safeguards (IDS) evolve in the future? The ability of the Agency to identify and resolve anomalies has always been important and has emerged as a core Agency function in recent years as the IAEA has had to deal with noncompliance in Iran and themore » Democratic People's Republic of Korea (DPRK). Future IAEA safeguards implementation should be designed with the goal of facilitating and enhancing this vital capability. In addition, the Agency should utilize all the information it possesses, including its in-house assessments and expertise, to direct its safeguards activities. At the State level, knowledge of proliferation possibilities is currently being used to guide the analytical activities of the Agency and to develop inspection plans. How far can this approach be extended? Does it apply across State boundaries? Should it dictate a larger fraction of safeguards activities? Future developments in IDS should utilize the knowledge resident within the Agency to ensure that safeguards resources flow to where they are most needed in order to address anomalies first and foremost, but also to provide greater confidence in conclusions regarding the absence of undeclared nuclear activities. The elements of such a system and related implementation issues are assessed in this paper.« less

Phase II: Field Detector Development For Undeclared/Declared Nuclear Testing For Treaty Verfiation Monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kriz, M.; Hunter, D.; Riley, T.

2015-10-02

Radioactive xenon isotopes are a critical part of the Comprehensive Nuclear Test Ban Treaty (CTBT) for the detection or confirmation of nuclear weapons tests as well as on-site treaty verification monitoring. On-site monitoring is not currently conducted because there are no commercially available small/robust field detector devices to measure the radioactive xenon isotopes. Xenon is an ideal signature to detect clandestine nuclear events since they are difficult to contain and can diffuse and migrate through soils due to their inert nature. There are four key radioxenon isotopes used in monitoring: 135Xe (9 hour half-life), 133mXe (2 day half-life), 133Xe (5more » day half-life) and 131mXe (12 day half-life) that decay through beta emission and gamma emission. Savannah River National Laboratory (SRNL) is a leader in the field of gas collections and has developed highly selective molecular sieves that allow for the collection of xenon gas directly from air. Phase I assessed the development of a small, robust beta-gamma coincidence counting system, that combines collection and in situ detection methodologies. Phase II of the project began development of the custom electronics enabling 2D beta-gamma coincidence analysis in a field portable system. This will be a significant advancement for field detection/quantification of short-lived xenon isotopes that would not survive transport time for laboratory analysis.« less

A Monte Carlo Analysis of Weight Data from UF 6 Cylinder Feed and Withdrawal Stations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garner, James R; Whitaker, J Michael

2015-01-01

As the number of nuclear facilities handling uranium hexafluoride (UF 6) cylinders (e.g., UF 6 production, enrichment, and fuel fabrication) increase in number and throughput, more automated safeguards measures will likely be needed to enable the International Atomic Energy Agency (IAEA) to achieve its safeguards objectives in a fiscally constrained environment. Monitoring the process data from the load cells built into the cylinder feed and withdrawal (F/W) stations (i.e., cylinder weight data) can significantly increase the IAEA’s ability to efficiently achieve the fundamental safeguards task of confirming operations as declared (i.e., no undeclared activities). Researchers at the Oak Ridge Nationalmore » Laboratory, Los Alamos National Laboratory, the Joint Research Center (in Ispra, Italy), and University of Glasgow are investigating how this weight data can be used for IAEA safeguards purposes while fully protecting the operator’s proprietary and sensitive information related to operations. A key question that must be resolved is, what is the necessary frequency of recording data from the process F/W stations to achieve safeguards objectives? This paper summarizes Monte Carlo simulations of typical feed, product, and tails withdrawal cycles and evaluates longer sampling frequencies to determine the expected errors caused by low-frequency sampling and its impact on material balance calculations.« less

Argon Collection And Purification For Proliferation Detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Achey, R.; Hunter, D.

2015-10-09

In order to determine whether a seismic event was a declared/undeclared underground nuclear weapon test, environmental samples must be taken and analyzed for signatures that are unique to a nuclear explosion. These signatures are either particles or gases. Particle samples are routinely taken and analyzed under the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO) verification regime as well as by individual countries. Gas samples are analyzed for signature gases, especially radioactive xenon. Underground nuclear tests also produce radioactive argon, but that signature is not well monitored. A radioactive argon signature, along with other signatures, can more conclusively determine whether an event wasmore » a nuclear test. This project has developed capabilities for collecting and purifying argon samples for ultra-low-background proportional counting. SRNL has developed a continuous gas enrichment system that produces an output stream containing 97% argon from whole air using adsorbent separation technology (the flow diagram for the system is shown in the figure). The vacuum swing adsorption (VSA) enrichment system is easily scalable to produce ten liters or more of 97% argon within twelve hours. A gas chromatographic separation using a column of modified hydrogen mordenite molecular sieve has been developed that can further purify the sample to better than 99% purity after separation from the helium carrier gas. The combination of these concentration and purification systems has the capability of being used for a field-deployable system for collecting argon samples suitable for ultra-low-background proportional counting for detecting nuclear detonations under the On-Site Inspection program of the CTBTO verification regime. The technology also has applications for the bulk argon separation from air for industrial purposes such as the semi-conductor industry.« less

Phenolic profiles of raw apricots, pumpkins, and their purees in the evaluation of apricot nectar and jam authenticity.

PubMed

Dragovic-Uzelac, Verica; Delonga, Karmela; Levaj, Branka; Djakovic, Senka; Pospisil, Jasna

2005-06-15

The possibility of proving the undeclared addition of pumpkin puree in apricot nectars and jams has been investigated by using the phenol compound fingerprint and sensory evaluation. The cheaper pumpkin admixtures in apricot nectars and jams could not be detected by the sensory evaluation, particularly if present in quantities of <15%. The lower admixtures of pumpkin puree in apricot nectars and jams could be detected by the presence of syringic acid, a phenolic compound characteristic of the investigated pumpkins (Cucurbita pepo cv. Gleisdorff and Table Gold, Cucurbita maxima cv. Turkinja, and Cucurbita moschata cv. Argenta). Syringic acid was isolated from pumpkin puree and determined by using HPLC with diode array detection. By using the phenolic profile, undeclared pumpkin admixture (> or =5%) in the apricot nectars and jams could be proven.

Detection of undeclared animal by-products in commercial canine canned foods: Comparative analyses by ELISA and PCR-RFLP coupled with slab gel electrophoresis or capillary gel electrophoresis.

PubMed

Hsieh, Ming-Kun; Shih, Pei-Yin; Wei, Chia-Fong; Vickroy, Thomas W; Chou, Chi-Chung

2016-03-30

The potential presence of undeclared animal by-products in pet foods is not subject to routine examination. Previously published methods for species-based identification of animal by-products have not been used routinely owing to inconsistent results. The present study evaluated the utility of several approaches for accurate identification of animal by-products in 11 commercial brands of canine canned foods. Canine canned foods from several countries were analysed by ELISA, PCR-RFLP coupled with slab-gel electrophoresis (SGE) and capillary gel electrophoresis (CGE) to test for evidence of by-products derived from cattle, chicken, sheep or pig. While CGE-based analysis detected all (24) animal-derived by-products that were reported for the 11 test samples, SGE and ELISA detected only 22/24 (92%) and 14/24 (58%) of labelled by-products, respectively. In addition, undeclared animal by-products were found using all three analytical approaches with CGE detecting more positives (19) than SGE (17) or ELISA (5). Significant disparities were evident between the labelled contents and the detected content of animal by-products. CGE-based testing for PCR products appears to provide greater sensitivity and accuracy than either SGE or ELISA-based methods. As testing of commercial products becomes more reliable and mainstream, manufacturers will need to develop more thorough and accurate labelling protocols. © 2015 Society of Chemical Industry.

Development of Metallic Magnetic Calorimeters for Nuclear Safeguards Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bates, Cameron Russell

2015-03-11

Many nuclear safeguards applications could benefit from high-resolution gamma-ray spectroscopy achievable with metallic magnetic calorimeters. This dissertation covers the development of a system for these applications based on gamma-ray detectors developed at the University of Heidelberg. It demonstrates new calorimeters of this type, which achieved an energy resolution of 45.5 eV full-width at half-maximum at 59.54 keV, roughly ten times better than current state of the art high purity germanium detectors. This is the best energy resolution achieved with a gamma-ray metallic magnetic calorimeter at this energy to date. In addition to demonstrating a new benchmark in energy resolution, anmore » experimental system for measuring samples with metallic magnetic calorimeters was constructed at Lawrence Livermore National Laboratory. This system achieved an energy resolution of 91.3 eV full-width at half-maximum at 59.54 keV under optimal conditions. Using this system it was possible to characterize the linearity of the response, the count-rate limitations, and the energy resolution as a function of temperature of the new calorimeter. With this characterization it was determined that it would be feasible to measure 242Pu in a mixed isotope plutonium sample. A measurement of a mixed isotope plutonium sample was performed over the course of 12 days with a single two-pixel metallic magnetic calorimeter. The relative concentration of 242Pu in comparison to other plutonium isotopes was determined by direct measurement to less than half a percent accuracy. This is comparable with the accuracy of the best-case scenario using traditional indirect methods. The ability to directly measure the relative concentration of 242Pu in a sample could enable more accurate accounting and detection of indications of undeclared activities in nuclear safeguards, a better constraint on source material in forensic samples containing plutonium, and improvements in verification in a future plutonium disposition treaty.« less

Contamination of animal feedingstuffs with undeclared antimicrobial additives.

PubMed

Lynas, L; Currie, D; McCaughey, W J; McEvoy, J D; Kennedy, D G

1998-01-01

A study was carried out on 397 feedingstuffs and 11 premixes on which 161 (39.5%) were declared free of medication and 247 (60.5%) were medicated. These were subjected to analysis for the presence of antibiotics. Of the 247 medicated feeds 87 (35.2%) contained undeclared antimicrobials of which 59 (23.9%) were at a concentration sufficient to allow quantification by HPLC. Of the 161 unmedicated feeds 71 (44.1%) were shown to contain detectable antimicrobials of which 42 (26.1%) contained concentrations which could be quantified by HPLC. The most frequently identified contaminating antimicrobials were chlortetracycline (CTC) (15.2%), sulphonamides (6.9%), penicillin (3.4%) and ionophores (3.4%). Four samples (ionophores--3, sulphadimidine--1) contained therapeutic concentrations and one sample a supra-therapeutic concentration (monensin). The remainder were sub-therapeutic. All the contaminating concentrations of sulphadimidine detected were sufficient to cause violative tissue residues if fed to animals immediately prior to slaughter.

An improved UPLC method for the detection of undeclared horse meat addition by using myoglobin as molecular marker.

PubMed

Di Giuseppe, Antonella M A; Giarretta, Nicola; Lippert, Martina; Severino, Valeria; Di Maro, Antimo

2015-02-15

In 2013, following the scandal of the presence of undeclared horse meat in various processed beef products across the Europe, several researches have been undertaken for the safety of consumer health. In this framework, an improved UPLC separation method has been developed to detect the presence of horse myoglobin in raw meat samples. The separation of both horse and beef myoglobins was achieved in only seven minutes. The methodology was improved by preparing mixtures with different composition percentages of horse and beef meat. By using myoglobin as marker, low amounts (0.50mg/0.50g, w/w; ∼0.1%) of horse meat can be detected and quantified in minced raw meat samples with high reproducibility and sensitivity, thus offering a valid alternative to conventional PCR techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

Monitoring and verification R&D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilat, Joseph F; Budlong - Sylvester, Kory W; Fearey, Bryan L

2011-01-01

The 2010 Nuclear Posture Review (NPR) report outlined the Administration's approach to promoting the agenda put forward by President Obama in Prague on April 5, 2009. The NPR calls for a national monitoring and verification R&D program to meet future challenges arising from the Administration's nonproliferation, arms control and disarmament agenda. Verification of a follow-on to New START could have to address warheads and possibly components along with delivery capabilities. Deeper cuts and disarmament would need to address all of these elements along with nuclear weapon testing, nuclear material and weapon production facilities, virtual capabilities from old weapon and existingmore » energy programs and undeclared capabilities. We only know how to address some elements of these challenges today, and the requirements may be more rigorous in the context of deeper cuts as well as disarmament. Moreover, there is a critical need for multiple options to sensitive problems and to address other challenges. There will be other verification challenges in a world of deeper cuts and disarmament, some of which we are already facing. At some point, if the reductions process is progressing, uncertainties about past nuclear materials and weapons production will have to be addressed. IAEA safeguards will need to continue to evolve to meet current and future challenges, and to take advantage of new technologies and approaches. Transparency/verification of nuclear and dual-use exports will also have to be addressed, and there will be a need to make nonproliferation measures more watertight and transparent. In this context, and recognizing we will face all of these challenges even if disarmament is not achieved, this paper will explore possible agreements and arrangements; verification challenges; gaps in monitoring and verification technologies and approaches; and the R&D required to address these gaps and other monitoring and verification challenges.« less

Strengthening IAEA Safeguards for Research Reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reid, Bruce D.; Anzelon, George A.; Budlong-Sylvester, Kory

During their December 10-11, 2013, workshop in Grenoble France, which focused on the history and future of safeguarding research reactors, the United States, France and the United Kingdom (UK) agreed to conduct a joint study exploring ways to strengthen the IAEA’s safeguards approach for declared research reactors. This decision was prompted by concerns about: 1) historical cases of non-compliance involving misuse (including the use of non-nuclear materials for production of neutron generators for weapons) and diversion that were discovered, in many cases, long after the violations took place and as part of broader pattern of undeclared activities in half amore » dozen countries; 2) the fact that, under the Safeguards Criteria, the IAEA inspects some reactors (e.g., those with power levels under 25 MWt) less than once per year; 3) the long-standing precedent of States using heavy water research reactors (HWRR) to produce plutonium for weapons programs; 4) the use of HEU fuel in some research reactors; and 5) various technical characteristics common to some types of research reactors that could provide an opportunity for potential proliferators to misuse the facility or divert material with low probability of detection by the IAEA. In some research reactors it is difficult to detect diversion or undeclared irradiation. In addition, infrastructure associated with research reactors could pose a safeguards challenge. To strengthen the effectiveness of safeguards at the State level, this paper advocates that the IAEA consider ways to focus additional attention and broaden its safeguards toolbox for research reactors. This increase in focus on the research reactors could begin with the recognition that the research reactor (of any size) could be a common path element on a large number of technically plausible pathways that must be considered when performing acquisition pathway analysis (APA) for developing a State Level Approach (SLA) and Annual Implementation Plan (AIP). To broaden the IAEA safeguards toolbox, the study recommends that the Agency consider closing potential gaps in safeguards coverage by, among other things: 1) adapting its safeguards measures based on a case-by-case assessment; 2) using more frequent and expanded/enhanced mailbox declarations (ideally with remote transmission of the data to IAEA Headquarters in Vienna) coupled with short-notice or unannounced inspections; 3) putting more emphasis on the collection and analysis of environmental samples at hot cells and waste storage tanks; 4) taking Safeguards by Design into account for the construction of new research reactors and best practices for existing research reactors; 5) utilizing fully all legal authorities to enhance inspection access (including a strengthened and continuing DIV process); and 6) utilizing new approaches to improve auditing activities, verify reactor operating data history, and track/monitor the movement and storage of spent fuel.« less

Species identification and quantification in meat and meat products using droplet digital PCR (ddPCR).

PubMed

Floren, C; Wiedemann, I; Brenig, B; Schütz, E; Beck, J

2015-04-15

Species fraud and product mislabelling in processed food, albeit not being a direct health issue, often results in consumer distrust. Therefore methods for quantification of undeclared species are needed. Targeting mitochondrial DNA, e.g. CYTB gene, for species quantification is unsuitable, due to a fivefold inter-tissue variation in mtDNA content per cell resulting in either an under- (-70%) or overestimation (+160%) of species DNA contents. Here, we describe a reliable two-step droplet digital PCR (ddPCR) assay targeting the nuclear F2 gene for precise quantification of cattle, horse, and pig in processed meat products. The ddPCR assay is advantageous over qPCR showing a limit of quantification (LOQ) and detection (LOD) in different meat products of 0.01% and 0.001%, respectively. The specificity was verified in 14 different species. Hence, determining F2 in food by ddPCR can be recommended for quality assurance and control in production systems. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Quantitative Digital Autoradiography for Environmental Swipe Sample Prioritization: System design, Characterization, and Initial Measurements

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDonald, Benjamin S.; Zalavadia, Mital A.; Miller, Brian W.

Environmental sampling and sample analyses by the International Atomic Energy Agency’s (IAEA) Network of Analytical Laboratories (NWAL) is a critical technical tool used to detect facility misuse under a Comprehensive Safeguards Agreement and to verify the absence of undeclared nuclear material activities under an Additional Protocol. Currently all environmental swipe samples (ESS) are screened using gamma spectrometry and x-ray fluorescence to estimate the amount of U and/or Pu in the ESS, to guide further analysis, and to assist in the shipment of ESS to the NWAL. Quantitative Digital Autoradiography for Environmental Samples (QDARES) is being developed to complement existing techniquesmore » through the use of a portable, real-time, high-spatial-resolution camera called the Ionizing-radiation Quantum Imaging Detector (iQID). The iQID constructs a spatial map of radionuclides within a sample or surface in real-time as charged particles (betas) and photons (gamma/x-rays) are detected and localized on an event-by-event basis. Knowledge of the location and nature of radioactive hot spots on the ESS could provide information for subsequent laboratory analysis. As a nondestructive technique, QDARES does not compromise the ESS chain of custody or subsequent laboratory analysis. In this paper we will present the system design and construction, characterization measurements with calibration sources, and initial measurements of ESS.« less

Adulteration of proprietary Chinese medicines and health products with undeclared drugs: experience of a tertiary toxicology laboratory in Hong Kong.

PubMed

Ching, Chor Kwan; Chen, Sammy Pak Lam; Lee, Hencher Han Chih; Lam, Ying Hoo; Ng, Sau Wah; Chen, Mo Lung; Tang, Magdalene Huen Yin; Chan, Suzanne Suk San; Ng, Candy Wai Yan; Cheung, Jana Wing Lan; Chan, Tina Yee Ching; Lau, Nike Kwai Cheung; Chong, Yeow Kuan; Mak, Tony Wing Lai

2018-01-01

Proprietary Chinese medicines (pCMs) and health products, generally believed to be natural and safe, are gaining popularity worldwide. However, the safety of pCMs and health products has been severely compromised by the practice of adulteration. The current study aimed to examine the problem of adulteration of pCMs and health products in Hong Kong. The present study was conducted in a tertiary referral clinical toxicology laboratory in Hong Kong. All cases involving the use of pCMs or health products, which were subsequently confirmed to contain undeclared adulterants, from 2005 to 2015 were reviewed retrospectively. A total of 404 cases involving the use of 487 adulterated pCMs or health products with a total of 1234 adulterants were identified. The adulterants consisted of approved drugs, banned drugs, drug analogues and animal thyroid tissue. The six most common categories of adulterants detected were nonsteroidal anti-inflammatory drugs (17.7%), anorectics (15.3%), corticosteroids (13.8%), diuretics and laxatives (11.4%), oral antidiabetic agents (10.0%) and erectile dysfunction drugs (6.0%). Sibutramine was the most common adulterant (n = 155). The reported sources of these illicit products included over-the-counter drug stores, the internet and Chinese medicine practitioners. A significant proportion of patients (65.1%) had adverse effects attributable to these illicit products, including 14 severe and two fatal cases. Psychosis, iatrogenic Cushing syndrome and hypoglycaemia were the three most frequently encountered adverse effects. Adulteration of pCMs and health products with undeclared drugs poses severe health hazards. Public education and effective regulatory measures are essential to address the problem. © 2017 The British Pharmacological Society.

44 CFR 204.43 - Ineligible costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Ineligible costs. 204.43... Ineligible costs. Costs not directly associated with the incident period are ineligible. Ineligible costs include the following: (a) Costs incurred in the mitigation, management, and control of undeclared fires...

A mass spectrometry method for the determination of the species of origin of gelatine in foods and pharmaceutical products.

PubMed

Grundy, H H; Reece, P; Buckley, M; Solazzo, C M; Dowle, A A; Ashford, D; Charlton, A J; Wadsley, M K; Collins, M J

2016-01-01

Gelatine is a component of a wide range of foods. It is manufactured as a by-product of the meat industry from bone and hide, mainly from bovine and porcine sources. Accurate food labelling enables consumers to make informed decisions about the food they buy. Since labelling currently relies heavily on due diligence involving a paper trail, there could be benefits in developing a reliable test method for the consumer industries in terms of the species origin of gelatine. We present a method to determine the species origin of gelatines by peptide mass spectrometry methods. An evaluative comparison is also made with ELISA and PCR technologies. Commercial gelatines were found to contain undeclared species. Furthermore, undeclared bovine peptides were observed in commercial injection matrices. This analytical method could therefore support the food industry in terms of determining the species authenticity of gelatine in foods. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Misdescription of packaged foods: a case study from the United Arab Emirates.

PubMed

Premanandh, J; Sabbagh, Aman; Maruthamuthu, M

2013-01-01

Food misdescription has become of paramount importance as consumers come into contact daily with a great variety of foods. The controversies surrounding genetically modified organism (GMO) labelling and malpractices in the food chain have forced regulatory authorities to authenticate food from production to consumption. This paper reports the results of a surveillance programme conducted in the United Arab Emirates (UAE) market to assess the status of food misdescription and authenticity. A DNA test was used to screen random samples of processed meat products bought from supermarkets in the UAE. A total of 246 samples were analysed from different geographical locations. The majority of samples showed a high standard of legal compliance, with over 95% confirmed for authenticity. However, 5% of samples were found to contain undeclared species. In conclusion, this study confirms the presence of undeclared food in the UAE market. Regular surveillance and monitoring programmes along with strict implementation of the Food and Adulteration Act may alleviate misdescription issues to a greater extent.

Technical solutions to nonproliferation challenges

NASA Astrophysics Data System (ADS)

Satkowiak, Lawrence

2014-05-01

The threat of nuclear terrorism is real and poses a significant challenge to both U.S. and global security. For terrorists, the challenge is not so much the actual design of an improvised nuclear device (IND) but more the acquisition of the special nuclear material (SNM), either highly enriched uranium (HEU) or plutonium, to make the fission weapon. This paper provides two examples of technical solutions that were developed in support of the nonproliferation objective of reducing the opportunity for acquisition of HEU. The first example reviews technologies used to monitor centrifuge enrichment plants to determine if there is any diversion of uranium materials or misuse of facilities to produce undeclared product. The discussion begins with a brief overview of the basics of uranium processing and enrichment. The role of the International Atomic Energy Agency (IAEA), its safeguard objectives and how the technology evolved to meet those objectives will be described. The second example focuses on technologies developed and deployed to monitor the blend down of 500 metric tons of HEU from Russia's dismantled nuclear weapons to reactor fuel or low enriched uranium (LEU) under the U.S.-Russia HEU Purchase Agreement. This reactor fuel was then purchased by U.S. fuel fabricators and provided about half the fuel for the domestic power reactors. The Department of Energy established the HEU Transparency Program to provide confidence that weapons usable HEU was being blended down and thus removed from any potential theft scenario. Two measurement technologies, an enrichment meter and a flow monitor, were combined into an automated blend down monitoring system (BDMS) and were deployed to four sites in Russia to provide 24/7 monitoring of the blend down. Data was downloaded and analyzed periodically by inspectors to provide the assurances required.

Technical solutions to nonproliferation challenges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Satkowiak, Lawrence

2014-05-09

The threat of nuclear terrorism is real and poses a significant challenge to both U.S. and global security. For terrorists, the challenge is not so much the actual design of an improvised nuclear device (IND) but more the acquisition of the special nuclear material (SNM), either highly enriched uranium (HEU) or plutonium, to make the fission weapon. This paper provides two examples of technical solutions that were developed in support of the nonproliferation objective of reducing the opportunity for acquisition of HEU. The first example reviews technologies used to monitor centrifuge enrichment plants to determine if there is any diversionmore » of uranium materials or misuse of facilities to produce undeclared product. The discussion begins with a brief overview of the basics of uranium processing and enrichment. The role of the International Atomic Energy Agency (IAEA), its safeguard objectives and how the technology evolved to meet those objectives will be described. The second example focuses on technologies developed and deployed to monitor the blend down of 500 metric tons of HEU from Russia's dismantled nuclear weapons to reactor fuel or low enriched uranium (LEU) under the U.S.-Russia HEU Purchase Agreement. This reactor fuel was then purchased by U.S. fuel fabricators and provided about half the fuel for the domestic power reactors. The Department of Energy established the HEU Transparency Program to provide confidence that weapons usable HEU was being blended down and thus removed from any potential theft scenario. Two measurement technologies, an enrichment meter and a flow monitor, were combined into an automated blend down monitoring system (BDMS) and were deployed to four sites in Russia to provide 24/7 monitoring of the blend down. Data was downloaded and analyzed periodically by inspectors to provide the assurances required.« less

76 FR 11569 - Hazardous Materials: Enhanced Enforcement Authority Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... harm Americans would move those materials as hidden shipments. Accordingly, although the presence of... statutory authority is not limited to undeclared shipments. On a broader scale, Section 7118 promotes the... commerce, when those employees have an objectively reasonable and articulable belief that the shipment may...

Undeclared Imports: Silent Borrowing in Educational Policy-Making and Research in Sweden

ERIC Educational Resources Information Center

Waldow, Florian

2009-01-01

Research on educational policy borrowing has mostly focused on explicit transfer processes, often highlighting how explicit reference to the international has served legitimatory purposes in the borrowing country. In contrast, this paper focuses on "silent" borrowing, i.e. non-acknowledged processes of policy transfer. The paper argues…

Psychopolitical Validity: Power, Culture, and Wellness

ERIC Educational Resources Information Center

Fisher, Adrian T.; Sonn, Christopher C.

2008-01-01

In this commentary, the authors review and critique Prilleltensky's model of psychopolitical validity and wellness. Although the overt recognition of power, oppression, and political forces are viewed most favorably, cautions are also given. Of most importance is the way in which his model is based in an undeclared North American model of…

USSP-IAEA WORKSHOP ON ADVANCED SENSORS FOR SAFEGUARDS.

DOE Office of Scientific and Technical Information (OSTI.GOV)

PEPPER,S.; QUEIROLO, A.; ZENDEL, M.

2007-11-13

The IAEA Medium Term Strategy (2006-2011) defines a number of specific goals in respect to the IAEA's ability to provide assurances to the international community regarding the peaceful use of nuclear energy through States adherences to their respective non-proliferation treaty commitments. The IAEA has long used and still needs the best possible sensors to detect and measure nuclear material. The Department of Safeguards, recognizing the importance of safeguards-oriented R&D, especially targeting improved detection capabilities for undeclared facilities, materials and activities, initiated a number of activities in early 2005. The initiatives included letters to Member State Support Programs (MSSPs), personal contactsmore » with known technology holders, topical meetings, consultant reviews of safeguards technology, and special workshops to identify new and novel technologies and methodologies. In support of this objective, the United States Support Program to IAEA Safeguards hosted a workshop on ''Advanced Sensors for Safeguards'' in Santa Fe, New Mexico, from April 23-27, 2007. The Organizational Analysis Corporation, a U.S.-based management consulting firm, organized and facilitated the workshop. The workshop's goal was to help the IAEA identify and plan for new sensors for safeguards implementation. The workshop, which was attended by representatives of seven member states and international organizations, included presentations by technology holders and developers on new technologies thought to have relevance to international safeguards, but not yet in use by the IAEA. The presentations were followed by facilitated breakout sessions where the participants considered two scenarios typical of what IAEA inspectors might face in the field. One scenario focused on an enrichment plant; the other scenario focused on a research reactor. The participants brainstormed using the technologies presented by the participants and other technologies known to them to propose techniques and methods that could be used by the IAEA to strengthen safeguards. Creative thinking was encouraged during discussion of the proposals. On the final day of the workshop, the OAC facilitators summarized the participant's ideas in a combined briefing. This paper will report on the results of the April 2007 USSP-IAEA Workshop on Advanced Sensors for Safeguards and give an overview of the proposed technologies of greatest promise.« less

Undeclared Wars: The Packaging of a National Security Strategy for the 1990’s

DTIC Science & Technology

1994-04-01

regarding shared or separation of powers between the executive and legislature. The issue became less of which branch of government was going to approve... separation of powers " in using military force in non-traditional roles can be found in the Constitution, as articulated by the Founding Fathers. 56

A cocktail of synthetic stimulants found in a dietary supplement associated with serious adverse events.

PubMed

Venhuis, Bastiaan; Keizers, Peter; van Riel, Antoinette; de Kaste, Dries

2014-06-01

Food supplements are regularly found to contain pharmacologically active substances. Recently, the food supplement Dexaprine was removed from the Dutch market because it was associated with severe adverse events. Reports to the Dutch Poisons Information Center (DPIC) showed that ingestion of as little as half a tablet caused several cases of nausea, agitation, tachycardia, and palpitations and even one case of cardiac arrest. The remaining tablets of four patients were sent in by different healthcare professionals. Analysis by ultra-performance liquid chromatography quadrupole time of flight mass-spectrometry (UPLC-QTOF-MS) confirmed the presence of synephrine, oxilofrine, deterenol, yohimbine, caffeine, and theophylline. Two more compounds were found which were tentatively identified as β-methyl-β-phenylethylamines. This incident is only the next in a series of similar incidents involving dietary supplements with (undeclared) active substances that are either unsafe or have no known safety profile. Copyright © 2014 John Wiley & Sons, Ltd.

An Exploration of Undeclared Students' Expectations of Experiences for Faculty Interactions and Co-Curricular Involvement

ERIC Educational Resources Information Center

Kittendorf, Lorie Anne

2012-01-01

Student persistence and achievement are areas of significant concern for institutions of higher education. With national college graduation rates hovering in the 50% range, it is important for colleges and universities to understand which student characteristics and campus environments lead to greater success, as well as the expectations students…

Interest-Divergence and the Colour of Cutbacks: Race, Recession and the Undeclared War on Black Children

ERIC Educational Resources Information Center

Gillborn, David

2013-01-01

Drawing on Critical Race Theory (CRT) and illustrating with examples from the English system, the paper addresses the hidden racist dimension to contemporary education reforms and argues that this is a predictable and recurrent theme at times of economic crisis. Derrick Bell's concept of "interest-convergence" argues that moments of…

Watershed Watch: The Importance of Mentors in Student-driven Full Inquiry Undergraduate Research Projects as the Foundation for an Introductory Course in Biogeoscience

NASA Astrophysics Data System (ADS)

Rock, B. N.; Hale, S. R.; Graham, K. J.; Hayden, L.; Barber, L.; Perry, C.; Schloss, J.; Sullivan, E.; Yuan, J.; Abebe, E.; Mitchell, L.; Abrams, E.; Gagnon, M.

2008-12-01

Watershed Watch (NSF 0525433) engages early undergraduate students from two-year and four-year colleges in student-driven full inquiry-based instruction in the biogeosciences. Program goals for Watershed Watch are to test if inquiry-rich student-driven projects sufficiently engage undeclared students (or noncommittal STEM majors) to declare a STEM major (or remain with their STEM major). A significant component of this program is an intensive two-week Summer course, in which undeclared freshmen research various aspects of a local watershed. Students develop their own research questions and study design, collect and analyze data, and produce a scientific or an oral poster presentation. The course objectives, curriculum and schedule are presented as a model for dissemination for other institutions and programs seeking to develop inquiry-rich courses designed to attract students into biogeoscience disciplines. Data from self-reported student feedback indicated the most important factors explaining high-levels of student motivation and research excellence in the course are 1) working with committed, energetic, and enthusiastic faculty mentors; and 2) faculty mentors demonstrating high degrees of teamwork and coordination.

Immunochemical-based method for detection of hazelnut proteins in processed foods.

PubMed

Ben Rejeb, Samuel; Abbott, Michael; Davies, David; Querry, Jessica; Cléroux, Chantal; Streng, Christine; Delahaut, Philippe; Yeung, Jupiter M

2003-01-01

A competitive enzyme-linked immunosorbent assay (ELISA) was developed to detect hazelnut by using polyclonal antibodies generated against a protein extract of roasted hazelnut. No cross-reactivity was observed in tests against 39 commodities, including many common allergens, tree nuts, and legumes. Hazelnut protein standard solutions at 0.45 ng/mL [inhibition concentration (IC80) of the competitive test] were clearly identified by the ELISA. An extraction and quantification method was developed and optimized for chocolate, cookies, breakfast cereals, and ice cream, major food commodities likely to be cross-contaminated with undeclared hazelnut during food processing. No sample cleanup was required when extracts were diluted 10-fold. Recovery results were generated with blank matrixes spiked at 4 levels from 1 to 10 microg/g hazelnut protein. With the developed extraction and sample handling procedure, hazelnut proteins were recovered at 64-83% from chocolate and at 78-97% from other matrixes. A confirmatory technique was developed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western transfer. The developed methods were applied to a small market survey of chocolate products and allowed the identification of undeclared hazelnut in these products.

Isolation and identification of a sibutramine analogue adulterated in slimming dietary supplements.

PubMed

Kim, Ji Won; Kweon, Soon Jae; Park, Seon Kyung; Kim, Jung Yeon; Lee, Ji Hyun; Han, Kyoung Moon; Cho, Sooyeul; Kim, Jinho; Han, Soon Young; Kim, Hyoung Ja; Kim, Woo Seong

2013-01-01

A suspected sibutramine analogue was detected in a slimming functional food by an ultra performance liquid chromatography-electrospray ionisation-time of flight mass spectrometry (UPLC-ESI-TOF/MS) method. The ultraviolet (UV) spectrum of this suspected compound showed close similarity to that of sibutramine. The sample was extracted with 70% MeOH and isolated by semi-preparative column chromatography. The structure of this compound was identified by spectroscopic analyses (nuclear magnetic resonance [NMR] technique, mass and tandem mass etc.). The structure of the unknown compound was demonstrated to be [(±)-dimethyl-1-[1-(3,4-dichlorophenyl)cyclobutyl]-N,N,3-trimethylbutan-1-amine (molecular formula C17H25NCl2) and named as chloro-sibutramine. Compared with sibutramine, it has one more chlorine atom than the 3-cholorophenyl group so was switched to 3,4-dichlorophenyl. Until now, chloro-sibutramine was isolated for the first time from the undeclared ingredient included in dietary supplements. Although the safety of chloro-sibutramine is unknown, there is a potential health risk to consumers because of a similar skeleton to sibutramine. For public health, this sibutramine analogue has been included in the inspection list of illegal adulterants in Korea.

Proliferation resistance of small modular reactors fuels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Polidoro, F.; Parozzi, F.; Fassnacht, F.

2013-07-01

In this paper the proliferation resistance of different types of Small Modular Reactors (SMRs) has been examined and classified with criteria available in the literature. In the first part of the study, the level of proliferation attractiveness of traditional low-enriched UO{sub 2} and MOX fuels to be used in SMRs based on pressurized water technology has been analyzed. On the basis of numerical simulations both cores show significant proliferation risks. Although the MOX core is less proliferation prone in comparison to the UO{sub 2} core, it still can be highly attractive for diversion or undeclared production of nuclear material. Inmore » the second part of the paper, calculations to assess the proliferation attractiveness of fuel in typical small sodium cooled fast reactor show that proliferation risks from spent fuel cannot be neglected. The core contains a highly attractive plutonium composition during the whole life cycle. Despite some aspects of the design like the sealed core that enables easy detection of unauthorized withdrawal of fissile material and enhances proliferation resistance, in case of open Non-Proliferation Treaty break-out, weapon-grade plutonium in sufficient quantities could be extracted from the reactor core.« less

PCR analysis of a prescription vegetarian diet and use in three dogs with cutaneous adverse food reactions.

PubMed

Aufox, Erin E; May, Elizabeth R; Frank, Linda A; Kania, Stephen A

2018-04-24

Cutaneous adverse food reaction (CAFR) is diagnosed by performing an elimination diet trial utilizing prescription or home-cooked diets followed by provocative challenge. To report findings of PCR analysis of a prescription vegetarian diet (RCV) for undeclared proteins of animal origin, as well as to describe its utilization for diagnosis and management of dogs suspected of having CAFR. Three client-owned dogs. PCR analysis of RCV for 11 mammalian species and poultry. In three dogs, clinical examination, cytology, aerobic culture (if indicated) and at least one elimination diet trial with RCV. In our case series, all dogs had a history of pruritus and recurrent pyoderma that resolved with infection control and an elimination diet trial. In cases 1 and 2, a diagnosis of CAFR was made following an elimination trial with RCV and provocative challenge. Case 3 had a previously confirmed diagnosis of CAFR and RCV was successfully used to maintain remission of CAFR-related signs. PCR testing of RCV was negative for 11 mammalian species and poultry. The RCV diet was found not to contain any undeclared mammalian or avian proteins. In this case series, the RCV was successfully used to diagnose and maintain three dogs with CAFR. © 2018 ESVD and ACVD.

Preprints, Impact Factors, and Unethical Behavior, but also Lots of Good News.

PubMed

Gölitz, Peter

2016-10-24

Preprints as well? There is already the Accepted Article (published directly after refereeing and author revision), the Early-View/ASAP-Version (after refereeing, editing and proofing), and the final Version of Record. The problems with preprints are discussed in this Editorial along with the undeclared resubmission of previously rejected manuscripts: publication times, color costs, and Angewandte Symposia are further topics. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stop the Insanity: Halt NATO Enlargement to Salvage Relations with Russia

DTIC Science & Technology

2009-02-12

America’s Undeclared War, 1918 -1920 (Dulles, VA: Brassey’s, 2003), iii. 9 For further discussion of Nazi operations within Russia, see Colonel...2009). 10 against communist authority, by the year’s end Bulgaria, Czechoslovakia, Hungary, Poland and Romania had joined East Germany in...Bucharest, Romania , 4 April 2008, http://www.kremlin.ru/eng/text/speeches/2008/04/04/1949_type82915_163150.shtml (accessed December 2008). 57 Adam

Watershed Watch: Using undergraduate student-driven inquiry-based research projects as a means of engaging undeclared students in the biogeosciences

NASA Astrophysics Data System (ADS)

Rock, B. N.; Hale, S.; Graham, K.; Hayden, L. B.

2009-12-01

Watershed Watch (NSF 0525433) engages early undergraduate students from two-year and four-year colleges in student-driven full inquiry-based instruction in the biogeosciences. Program goals for Watershed Watch are to test if inquiry-rich student-driven projects sufficiently engage undeclared students (or noncommittal STEM majors) to declare a STEM major (or remain with their STEM major). The program is a partnership between two four-year campuses - the University of New Hampshire (UNH), and Elizabeth City State University (ECSU, in North Carolina); and two two-year campuses - Great Bay Community College (GBCC, in New Hampshire) and the College of the Albemarle (COA, in North Carolina). The program focuses on two watersheds: the Merrimack Ricer Watershed in New Hampshire and Massachusetts, and the Pasquotank River Watershed in Virginia and North Carolina. Both the terrestrial and aquatic components of both watersheds are evaluated using the student-driven projects. A significant component of this program is an intensive two-week Summer Research Institute (SRI), in which undeclared freshmen and sophomores investigate various aspects of their local watershed. Two Summer Research Institutes have been held on the UNH campus (2006 and 2008) and two on the ECSU campus (2007 and 2009). Students develop their own research questions and study design, collect and analyze data, and produce a scientific oral or poster presentation on the last day of the SRI. The course objectives, curriculum and schedule are presented as a model for dissemination for other institutions and programs seeking to develop inquiry-rich programs or courses designed to attract students into biogeoscience disciplines. Data from self-reported student feedback indicate the most important factors explaining high-levels of student motivation and research excellence in the program are: 1) working with committed, energetic, and enthusiastic faculty mentors, and 2) faculty mentors demonstrating high degrees of teamwork and coordination. The past four Summer Research Institutes have engaged over 100 entry-level undergraduate students in the process of learning science by doing it, and approximately 50% of those participating have declared majors in a wide range of science fields. A total of eight Watershed Watch students have presented findings from their SRI research projects at AGU meetings in 2007, 2008, and 2009. This presentation will highlight the lessons learned over the past four years in the Watershed Watch program.

JPRS Report, Near East & South Asia

DTIC Science & Technology

1990-11-08

INTERNATIONAL AFFAIRS Undeclared Strategic Agendas in Gulf 91AE0085A Tel Aviv YEDI’OT AHARONOT in Hebrew 30 Oct 90 pp 7, 25 [Article by Ron Ben...faithful representative of the " bible belt" in the southern United States. It is currently difficult to know who initiated the Saudi deals. Was it the...state. JPRS-NEA-90-066 8 NOVEMBER 1990 NEAR EAST 13 ISRAEL Columnist Examines U.S. Middle East Policy 91AE0038B Tel Aviv MA’ARIV in Hebrew

LLNL Contribution to Sandia Used Fuel Disposition - Security March 2011 Deliverable

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blink, J A

2011-03-23

Cleary [2007] divides the proliferation pathway into stages: diversion, facility misuse, transportation, transformation, and weapons fabrication. King [2010], using Cleary's methodology, compares a deepburn fusion-driven blanket containing weapons-grade plutonium with a PWR burning MOX fuel enrichments of 5-9%. King considers the stages of theft, transportation, transformation, and nuclear explosive fabrication. In the current study of used fuel storage security, a similar approach is appropriate. First, one must consider the adversary's objective, which can be categorized as on-site radionuclide dispersion, theft of material for later radionuclide dispersion, and theft of material for later processing and fabrication into a nuclear explosive. Formore » on-site radionuclide dispersion, only a single proliferation pathway stage is appropriate: dispersion. That situation will be addressed in future reports. For later radionuclide dispersion, the stages are theft, transportation, and transformation (from oxide spent fuel containing both fission products and actinides to a material size and shape suitable for dispersion). For later processing and fabrication into a nuclear explosive, the stages are theft (by an outsider or by facility misuse by an insider), transportation, transformation (from oxide spent fuel containing both fission products and actinides to a metal alloy), and fabrication (of the alloy into a weapon). It should be noted that the theft and transportation stages are similar, and possibly identical, for later radionuclide dispersion and later processing and fabrication into a nuclear explosive. Each stage can be evaluated separately, and the methodology can vary for each stage. For example, King starts with the methodology of Cleary for the theft, transportation, transformation, and fabrication stages. Then, for each stage, King assembles and modifies the attributes and inputs suggested by Cleary. In the theft (also known as diversion) stage, Cleary has five high-level categories (material handling during diversion, difficulty of evading detection by the accounting system, difficulty of evading detection by the material control system, difficulty of conducting undeclared facility modifications for the purpose of diverting nuclear material, and difficulty of evading detection of the facility modifications for the purposes of diverting nuclear material). Each category has one or more subcategories. For example, the first category includes mass per significant quantity (SQ) of nuclear material, volume/SQ of nuclear material, number of items/SQ, material form (solid, liquid, powder, gas), radiation level in terms of dose, chemical reactivity, heat load, and process temperature. King adds the following two subcategories to that list: SQs available for theft, and interruptions/changes (normal and unexpected) in material stocks and flows. For the situation of an orphaned surface storage facility, this approach is applicable, with some of the categories and subcategories being modified to reflect the static situation (no additions or removals of fuel or containers). In addition, theft would require opening a large overpack and either removing a full container or opening that sealed container and then removing one or more spent nuclear fuel assemblies. These activities would require time without observation (detection), heavy-duty equipment, and some degree of protection of the thieves from radiological dose. In the transportation stage, Cleary has two high-level categories (difficulty of handling material during transportation, and difficulty of evading detection during transport). Each category has a number of subcategories. For the situation of an orphaned surface storage facility, these categories are applicable. The transformation stage of Cleary has three high-level categories (facilities and equipment needed to process diverted materials; knowledge, skills, and workforce needed to process diverted materials; and difficulty of evading detection of transformation activities). Again, there are subcategories. King [2007] adds a fourth high-level category: time required to transform the materials. For the situation of an orphaned surface storage facility, the categories are applicable, but the evaluations of each category and subcategory will be significantly different for later radionuclide dispersion than for later processing and fabrication into a nuclear explosive. The fabrication stage of Cleary has three high-level categories (difficulty associated with design, handling difficulties, and knowledge and skills needed to design and fabricate). King replaces the first two high-level categories with the Figure of Merit for Nuclear Explosives Utility (FOM), with subcategories of bare critical mass, heat content of transformed material, dose rate of transformed material, and SQs available for theft. The next section of this report describes the FOM in more detail.« less

Analysis of U.S. Food and Drug Administration food allergen recalls after implementation of the food allergen labeling and consumer protection act.

PubMed

Gendel, Steven M; Zhu, Jianmei

2013-11-01

To avoid potentially life-threatening reactions, food allergic consumers rely on information on food labels to help them avoid exposure to a food or ingredient that could trigger a reaction. To help consumers in the United States obtain the information that they need, the Food Allergen Labeling and Consumer Protection Act of 2004 defined a major food allergen as being one of eight foods or food groups and any ingredient that contains protein from one of these foods or food groups. A food that contains an undeclared major food allergen is misbranded under the U.S. Food, Drug, and Cosmetic Act and is subject to recall. Food allergen labeling problems are the most common cause of recalls for U.S. Food and Drug Administration (FDA)-regulated food products. To help understand why food allergen recalls continue to occur at a high rate, information on each food allergen recall that occurred in fiscal years 2007 through 2012 was obtained from the FDA recall database. This information was analyzed to identify the food, allergen, root cause, and mode of discovery for each food allergen recall. Bakery products were the most frequently recalled food type, and milk was the most frequently undeclared major food allergen. Use of the wrong package or label was the most frequent problem leading to food allergen recalls. These data are the first reported that indicate the importance of label and package controls as public health measures.

Uranium Enrichment Safeguards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demuth, Scott F.; Trahan, Alexis Chanel

2017-06-26

DIV of facility layout, material flows, and other information provided in the DIQ. Material accountancy through an annual PIV and a number of interim inventory verifications, including UF6 cylinder identification and counting, NDA of cylinders, and DA on a sample collection of UF6. Application of C/S technologies utilizing seals and tamper-indicating devices (TIDs) on cylinders, containers, storage rooms, and IAEA instrumentation to provide continuity of knowledge between inspection. Verification of the absence of undeclared material and operations, especially HEU production, through SNRIs, LFUA of cascade halls, and environmental swipe sampling

Chinese proprietary medicine in Singapore: regulatory control of toxic heavy metals and undeclared drugs.

PubMed

Koh, H L; Woo, S O

2000-11-01

Traditional Chinese medicine (TCM) is gaining popularity as a form of complementary and alternative medicine. Reports of efficacy of TCM are increasing in numbers. TCM includes both crude Chinese medicinal materials (plants, animal parts and minerals) and Chinese proprietary medicine (CPM) [final dosage forms]. Despite the belief that CPM and herbal remedies are of natural origin, unlike Western medicine, and are hence safe and without many adverse effects, there have been numerous reports of adverse effects associated with herbal remedies. Factors affecting the safety of herbal medicines include intrinsic toxicity, adulteration, substitution, contamination, misidentification, lack of standardisation, incorrect preparation and/or dosage and inappropriate labelling and/or advertising. Hence, new regulations on the control of CPM were enforced in Singapore with effect from 1 September 1999. These include licensing and labelling requirements, as well as control of microbial contamination. This article also reviews reports of excessive toxic heavy metals and undeclared drugs in CPM in Singapore between 1990 and 1997. The names, uses, toxic heavy metal or drug detected and the year of detection are tabulated. Information on the brand or manufacturer's name are provided whenever available. The public and healthcare professionals should be better informed of the basic concept of TCM and its usefulness, as well as the potential adverse effects associated with its use. Greater control over the safety and quality of CPM could be achieved through good manufacturing practice, regulatory control, research, education, reporting usage of Chinese medicine (as in drug history) as well as reporting of adverse events.

Determination of mammalian deoxyribonucleic acid (DNA) in commercial vegetarian and vegan diets for dogs and cats.

PubMed

Kanakubo, K; Fascetti, A J; Larsen, J A

2017-02-01

The determination of undeclared ingredients in pet food using different analytical methods has been reported in recent years, raising concerns regarding adequate quality control, dietary efficacy and the potential for purposeful adulteration. The objective of this study was to determine the presence or absence of mammalian DNA using multiplex polymerase chain reaction (PCR) on diets marketed as vegetarian or vegan for dogs and cats. The diets were tested in duplicate; two samples were purchased approximately 3 to 4 months apart with different lot numbers. Multiplex PCR-targeted mitochondrial DNA with two species-specific primers was used to amplify and sequence two sections of the cytochrome b gene for each of the 11 mammalian species. Half of the diets assessed (7/14) were positive for one or more undeclared mammalian DNA source (bovine, porcine, or ovine), and the result was repeatable for one or more species in six diets. While most of the detected DNA was found at both time points, in some cases, the result was positive only at one time point, suggesting the presence may have been due to unintentional cross-contact with animal-sourced ingredients. DNA from feline, cervine, canine, caprine, equine, murine (mouse and rat) and leporine was not identified in any samples. However, evidence of mammalian DNA does not confirm adulteration by the manufacturer nor elucidate its clinical significance when consumed by animals that may benefit from a vegetarian or vegan diet. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Gas centrifuge enrichment plants inspection frequency and remote monitoring issues for advanced safeguards implementation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyer, Brian David; Erpenbeck, Heather H; Miller, Karen A

2010-09-13

Current safeguards approaches used by the IAEA at gas centrifuge enrichment plants (GCEPs) need enhancement in order to verify declared low enriched uranium (LEU) production, detect undeclared LEU production and detect high enriched uranium (BEU) production with adequate probability using non destructive assay (NDA) techniques. At present inspectors use attended systems, systems needing the presence of an inspector for operation, during inspections to verify the mass and {sup 235}U enrichment of declared cylinders of uranium hexafluoride that are used in the process of enrichment at GCEPs. This paper contains an analysis of how possible improvements in unattended and attended NDAmore » systems including process monitoring and possible on-site destructive analysis (DA) of samples could reduce the uncertainty of the inspector's measurements providing more effective and efficient IAEA GCEPs safeguards. We have also studied a few advanced safeguards systems that could be assembled for unattended operation and the level of performance needed from these systems to provide more effective safeguards. The analysis also considers how short notice random inspections, unannounced inspections (UIs), and the concept of information-driven inspections can affect probability of detection of the diversion of nuclear material when coupled to new GCEPs safeguards regimes augmented with unattended systems. We also explore the effects of system failures and operator tampering on meeting safeguards goals for quantity and timeliness and the measures needed to recover from such failures and anomalies.« less

All in the name of flavour, fragrance & freshness: Commonly used smokeless tobacco preparations in & around a tertiary hospital in India

PubMed Central

Dwivedi, Shridhar; Aggarwal, Amitesh; Dev, Munish

2012-01-01

Background & objectives: There is a general misconception that smokeless tobacco particularly sweetened and flavoured paan masala and gutkas are safe to use. The present study was undertaken with the objective of highlighting the deceptive and aggressive marketing techniques adopted by the manufacturers of smokeless tobacco preparations exploiting cultural, social and religious values. Another object was to highlight the lack of transparency in terms of content, weight, quality control and warning. Methods: All empty pouches of the used paan masalas, gutka, khaini or surti in and around a tertiary care hospital at east Delhi were collected. Their constituents were studied as per written declaration by the manufacturers on each packet. Information on net weight, cost, presence and type of warning, and quality assurance on each brand provided on side of the packets was noted. Results: A total of 1136 pouches of 33 brands/varieties were collected. Most of the gutka preparations contained tobacco, betel nut, unknown flavouring agents, undeclared spices and heavy metals. Warning regarding the harmful effect of tobacco was written in 90.9 per cent of brands with 81.8 per cent in English language only in minute font. Contents of the products were mentioned in 84.8 per cent of brands and only 27.3 per cent of those mentioned the net weight of the ingredients. Interpretation & conclusions: Seemingly ‘innocuous’ tobacco preparations in the form of paan masalas, gutka, khaini, surti or mouth fresheners contain various harmful substance like tobacco, betel nut, sugar coated fennel, saccharine, heavy metals like silver, unknown flavouring agents and undeclared spices in unknown quantities. Lack of transparency in terms of content, weight, quality control and warning is duping unsuspecting consumers. PMID:23287132

Did the tobacco industry inflate estimates of illicit cigarette consumption in Asia? An empirical analysis.

PubMed

Chen, Jing; McGhee, Sarah M; Townsend, Joy; Lam, Tai Hing; Hedley, Anthony J

2015-06-01

Estimates of illicit cigarette consumption are limited and the data obtained from studies funded by the tobacco industry have a tendency to inflate them. This study aimed to validate an industry-funded estimate of 35.9% for Hong Kong using a framework taken from an industry-funded report, but with more transparent data sources. Illicit cigarette consumption was estimated as the difference between total cigarette consumption and the sum of legal domestic sales and legal personal imports (duty-free consumption). Reliable data from government reports and scientifically valid routine sources were used to estimate the total cigarette consumption by Hong Kong smokers and legal domestic sales in Hong Kong. Consumption by visitors and legal duty-free consumption by Hong Kong passengers were estimated under three scenarios for the assumptions to examine the uncertainty around the estimate. A two-way sensitivity analysis was conducted using different levels of possible undeclared smoking and under-reporting of self-reported daily consumption. Illicit cigarette consumption was estimated to be about 8.2-15.4% of the total cigarette consumption in Hong Kong in 2012 with a midpoint estimate of 11.9%, as compared with the industry-funded estimate of 35.9% of cigarette consumption. The industry-funded estimate was inflated by 133-337% of the probable true value. Only with significant levels of under-reporting of daily cigarette consumption and undeclared smoking could we approximate the value reported in the industry-funded study. The industry-funded estimate inflates the likely levels of illicit cigarette consumption. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Survey of undeclared egg allergen levels in the most frequently recalled food types (including products bearing precautionary labelling).

PubMed

Khuda, Sefat E; Sharma, Girdhari M; Gaines, Dennis; Do, Andrew B; Pereira, Marion; Chang, Michael; Ferguson, Martine; Williams, Kristina M

2016-08-01

Since the number of recalls involving undeclared allergens is commonly associated with bakery and snack foods, we aimed to determine the frequency of egg allergens in a large number of these products using two commercial enzyme-linked immunosorbent assay (ELISA) methods. Samples were chosen that either had no egg identified on the product label or which had an egg precautionary statement. Among all samples, egg protein was detected in 5% of products using a Morinaga (MO) kit and 1% of products using a R-Biopharm (RB) kit. For bakery samples, egg protein was detected in 6% of 363 samples with no precautionary labelling (6% by MO and 1% by RB kit) and 12% of 80 samples which had precautionary labelling. For snack samples, egg protein was detected in 2% of 371 samples with no precautionary labelling (2% by MO and < 1% by RB kit) and 5% of 21 samples which had precautionary labelling. The disagreement rates between two methods were 5.2% for bakery products and 2.6% for snack products. The sample repeatability was at an acceptable level for bakery (< 12.5%) and snack foods (< 7.5%) for each method. The relative standard deviation between test kits was high (103.1%) for bakery foods. Four bakery products without precautionary labelling had a higher level of egg protein per serving compared with the eliciting dose (ED10 of 3.7 mg protein) for egg allergic patients. These results highlight the fact that detection methodology plays a vital role for accurate labelling control and mitigation of risk for egg allergic consumers.

Analysis and critical comparison of food allergen recalls from the European Union, USA, Canada, Hong Kong, Australia and New Zealand.

PubMed

Bucchini, Luca; Guzzon, Antonella; Poms, Roland; Senyuva, Hamide

2016-05-01

As part of a European Union-funded project (FP7) developing 'Integrated approaches to food allergen and allergy management', a database was constructed based on publicly available information on food allergen recalls in Europe, North America, Hong Kong, Australia and New Zealand. Over 2000 entries were made into the database. The database covers a 4-year period from 2011 to 2014 and each entry is categorised into food type (two different classifications), identified allergen and cause where indicated by the authorities. Across different authorities, by far the biggest incidence of undeclared allergens occurred in the food categories of prepared dishes and snacks (range = 12-53%), and cereals and bakery products (range = 14-25% of all recalls and/or alerts). The biggest incidence of undeclared allergens, according to the information from most authorities, occurred for milk and milk products (16-31% of all products with recall or alert), followed by cereals containing gluten (9-19%), soy (5-45%), and egg and egg products (5-17%). Although 42-90% of the products with recalls/alerts were explained as being 'Not indicated on the label', this is a generic explanation of cause and does not provide much insight into the causes of the recall/alerts. However, 0-17% of products with recalls/alerts could be coded as caused by the unintended presence of an allergen as the probable result of cross-contact in production. Construction of the database of allergen recalls has provided some important lessons and recommendations to the authorities are made in this paper in terms of the harmonisation of the reporting of allergen recalls into a more standardised format.

Undeclared exposure to St. John's Wort in hospitalized patients

PubMed Central

Martin-Facklam, Meret; Rieger, Karin; Riedel, Klaus-Dieter; Burhenne, Jürgen; Walter-Sack, Ingeborg; Haefeli, Walter E

2004-01-01

Aim The herbal medicine St. John's Wort (SJW) causes substantial decreases in the plasma concentrations of a range of co-administered drugs. Therefore, we evaluated the extent of systemic exposure to hyperforin and hypericin, two of the main constituents of SJW, in patients on admission and during hospital stay, and compared the results with known use of SJW as documented in the drug chart and detected in additional interviews. Methods One hundred and fifty patients aged ≥ 18 years and admitted, between August 2000 and February 2002, to an internal medicine ward of a large German university hospital were included. Hyperforin and hypericin was determined in plasma by a sensitive liquid chromotography/mass spectometry (LC/MS/MS) method. To assess undeclared use of SJW the data were compared to information obtained from drug charts and from up to three interviews that had a particular focus on intake of herbal medicines and self-medication during hospitalization. Results Hyperforin was detected in 12 patients (plasma concentration on the first day of hospitalization = 12–100 ng ml−1 in five patients and <3 ng ml−1 in seven), and hypericin in five patients (0.5–4.3 ng ml−1). Nine patients (6%) were taking/had taken SJW without the knowledge of the medical team and the pharmacist, who conducted the additional interviews, and 11 (7.3%) were taking/had taken SJW without the knowledge of the medical team alone. Seven of these patients were treated concurrently with drugs that can interact with SJW. Conclusions Unrecognized use of SJW is frequent and may have an important influence on the effectiveness and safety of drug therapy during hospital stay. PMID:15373938

Ecdysteroid-containing food supplements from Cyanotis arachnoidea on the European market: evidence for spinach product counterfeiting

NASA Astrophysics Data System (ADS)

Hunyadi, Attila; Herke, Ibolya; Lengyel, Katalin; Báthori, Mária; Kele, Zoltán; Simon, András; Tóth, Gábor; Szendrei, Kálmán

2016-12-01

Phytoecdysteroids like 20-hydroxyecdysone (“ecdysterone”) can exert a mild, non-hormonal anabolic/adaptogenic activity in mammals, and as such, are frequently used in food supplements. Spinach is well-known for its relatively low ecdysteroid content. Cyanotis arachnoidea, a plant native in China, is among the richest sources of phytoecdysteroids, and extracts of this plant are marketed in tons per year amounts via the internet at highly competitive prices. Here we report the investigation of a series of food supplements produced in Germany and claimed to contain spinach extracts. Twelve ecdysteroids including two new compounds were isolated and utilized as marker compounds. A comparative analysis of the products with Cyanotis and spinach extracts provides evidence that they were manufactured from Cyanotis extracts instead of spinach as stated. Based on the chromatographic fingerprints, 20-hydroxyecdysone 2- and 3-acetate are suggested as diagnostic markers for related quality control. This case appears to represent an unusual type of dietary supplement counterfeiting: undeclared extracts from alternative plants would supposedly ‘guarantee’ product efficacy.

Strengthened IAEA Safeguards-Imagery Analysis: Geospatial Tools for Nonproliferation Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pabian, Frank V

2012-08-14

This slide presentation focuses on the growing role and importance of imagery analysis for IAEA safeguards applications and how commercial satellite imagery, together with the newly available geospatial tools, can be used to promote 'all-source synergy.' As additional sources of openly available information, satellite imagery in conjunction with the geospatial tools can be used to significantly augment and enhance existing information gathering techniques, procedures, and analyses in the remote detection and assessment of nonproliferation relevant activities, facilities, and programs. Foremost of the geospatial tools are the 'Digital Virtual Globes' (i.e., GoogleEarth, Virtual Earth, etc.) that are far better than previouslymore » used simple 2-D plan-view line drawings for visualization of known and suspected facilities of interest which can be critical to: (1) Site familiarization and true geospatial context awareness; (2) Pre-inspection planning; (3) Onsite orientation and navigation; (4) Post-inspection reporting; (5) Site monitoring over time for changes; (6) Verification of states site declarations and for input to State Evaluation reports; and (7) A common basis for discussions among all interested parties (Member States). Additionally, as an 'open-source', such virtual globes can also provide a new, essentially free, means to conduct broad area search for undeclared nuclear sites and activities - either alleged through open source leads; identified on internet BLOGS and WIKI Layers, with input from a 'free' cadre of global browsers and/or by knowledgeable local citizens (a.k.a.: 'crowdsourcing'), that can include ground photos and maps; or by other initiatives based on existing information and in-house country knowledge. They also provide a means to acquire ground photography taken by locals, hobbyists, and tourists of the surrounding locales that can be useful in identifying and discriminating between relevant and non-relevant facilities and their associated infrastructure. The digital globes also provide highly accurate terrain mapping for better geospatial context and allow detailed 3-D perspectives of all sites or areas of interest. 3-D modeling software (i.e., Google's SketchUp6 newly available in 2007) when used in conjunction with these digital globes can significantly enhance individual building characterization and visualization (including interiors), allowing for better assessments including walk-arounds or fly-arounds and perhaps better decision making on multiple levels (e.g., the best placement for International Atomic Energy Agency (IAEA) video monitoring cameras).« less

Improved Overpressure Recording and Modeling for Near-Surface Explosion Forensics

NASA Astrophysics Data System (ADS)

Kim, K.; Schnurr, J.; Garces, M. A.; Rodgers, A. J.

2017-12-01

The accurate recording and analysis of air-blast acoustic waveforms is a key component of the forensic analysis of explosive events. Smartphone apps can enhance traditional technologies by providing scalable, cost-effective ubiquitous sensor solutions for monitoring blasts, undeclared activities, and inaccessible facilities. During a series of near-surface chemical high explosive tests, iPhone 6's running the RedVox infrasound recorder app were co-located with high-fidelity Hyperion overpressure sensors, allowing for direct comparison of the resolution and frequency content of the devices. Data from the traditional sensors is used to characterize blast signatures and to determine relative iPhone microphone amplitude and phase responses. A Wiener filter based source deconvolution method is applied, using a parameterized source function estimated from traditional overpressure sensor data, to estimate system responses. In addition, progress on a new parameterized air-blast model is presented. The model is based on the analysis of a large set of overpressure waveforms from several surface explosion test series. An appropriate functional form with parameters determined empirically from modern air-blast and acoustic data will allow for better parameterization of signals and the improved characterization of explosive sources.

Application of HRAM screening and LC-MS/MS confirmation of active pharmaceutical ingredient in "natural" herbal supplements.

PubMed

Pascali, Jennifer P; Fais, Paolo; Vaiano, Fabio; Bertol, Elisabetta

2018-05-01

The growing market of herbal remedies worldwide could pose severe problems to consumers' health due to the possible presence of potentially harmful, undeclared synthetic substances or analogues of prescription drugs. The present work shows a simple but effective approach to unequivocally identify synthetic anorectic compounds in allegedly 'natural' herbal extracts, by exploiting liquid chromatography/time of flight (Q-TOF LC/MS) technology coupled to liquid chromatography/triple quadrupole (LC-MS/MS) confirmation and quantitation. The procedure was applied to five tea herbal extracts and pills sold as coadjutant for weigh loss. The method exploited liquid-liquid sample extraction (LLE) and separation in a C18 (2.1mm×150mm, 1.8μm) column. QTOF acquisitions were carried out both in scan mode and all ion MS/MS mode and results were obtained after search against ad hoc prepared library. Sibutramine, 4-hydroxyamphetamine, caffeine and theophylline were preliminary identified samples. Confirmation and quantitation of the preliminary identified compounds were obtained in LC-MS/MS after preparation of appropriated standards. Sibutramine, caffeine and theophylline were finally confirmed and quantitate. Copyright © 2018 Elsevier B.V. All rights reserved.

Sandwich enzyme-linked immunosorbent assay (ELISA) for detection of cashew nut in foods.

PubMed

Gaskin, Ferdelie E; Taylor, Steve L

2011-01-01

The presence of undeclared cashew can pose a health risk to cashew-allergic consumers. The food industry has the responsibility to declare the presence of cashews on packaged foods even when trace residues are or might be present. The objective of this study was to develop a rapid, sensitive, and specific enzyme-linked immunosorbent assay (ELISA) for the detection of cashew residues. Raw and roasted cashews were defatted and used separately to immunize sheep, goats, and rabbits. The cashew ELISA was developed using sheep and rabbit polyclonal anti-roasted cashew sera as capture and detector reagents, respectively, with visualization through an alkaline phosphatase-mediated substrate reaction. The cashew ELISA was shown to have a limit of quantification of 1 ppm (1 μg cashew/g). The ELISA was highly specific except that substantial cross-reactivity was noted with pistachio and a lesser degree of cross-reactivity was noted with hazelnut. The performance of the ELISA was assessed by manufacturing cookies, ice cream, and milk chocolate with added known amounts (0 to 1000 ppm) of cashew. The mean percent recoveries for ice cream, cookies, and milk chocolate were 118%± 2.9%, 84.3%± 4.0%, and 104%± 3.0%, respectively. In a limited retail survey, 4/5 retail samples with cashew declared on ingredient labels tested positive for cashew compared to 5/36 samples of foods with precautionary labels indicating the possible presence of one or more tree nuts and 0/18 samples without cashew declared on the label in any manner. The cashew ELISA can be used to detect undeclared cashew residue in foods and as a potential tool for the food industry to assess the effectiveness of allergen control strategies and to guarantee compliance with food labeling regulatory requirements. © 2011 Institute of Food Technologists®

Mismatches in genetic markers in a large family study.

PubMed Central

Ashton, G C

1980-01-01

The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biological parent were used to determine the rate of undeclared nonparentage in 1,748 families in which conventional relationships were claimed. Two independent approaches gave consistent estimates, suggesting that approximately 2.3% of the 2,839 tested children from these families were probably the result of infidelity, concealed adoption, or another event. About two-thirds of the mismatches detected were probably due to properties of the techniques employed. PMID:6930820

State machine analysis of sensor data from dynamic processes

DOEpatents

Cook, William R.; Brabson, John M.; Deland, Sharon M.

2003-12-23

A state machine model analyzes sensor data from dynamic processes at a facility to identify the actual processes that were performed at the facility during a period of interest for the purpose of remote facility inspection. An inspector can further input the expected operations into the state machine model and compare the expected, or declared, processes to the actual processes to identify undeclared processes at the facility. The state machine analysis enables the generation of knowledge about the state of the facility at all levels, from location of physical objects to complex operational concepts. Therefore, the state machine method and apparatus may benefit any agency or business with sensored facilities that stores or manipulates expensive, dangerous, or controlled materials or information.

Examination of psychological variables related to nuclear attitudes and nuclear activism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roy, P.J.

1985-01-01

It was hypothesized that knowledge about nuclear arms developments would not be correlated with nuclear attitudes, that sense of efficacy would be positively correlated with magnitude of nuclear activism, and that death anxiety would be correlated with high level of nuclear knowledge and anti-nuclear attitudes, but not with sense of power. It was also hypothesized that positive correlations would be found between nuclear activism and political activism, knowledge of nuclear facts, and degree of adherence to anti-nuclear attitudes. One hundred and forty three women and 90 men participated in this questionnaire study. Major findings are as follows. In general, themore » more people knew about nuclear developments, the more anti-nuclear were their attitudes. Also, regardless of nuclear attitudes, a positive correlation was found between knowledge of nuclear facts and nuclear activism. Death anxiety and powerlessness were not correlated. There was a positive correlation between anxiety and both nuclear knowledge and anti-nuclear attitudes. A strong positive correlation was found between nuclear activism and anti-nuclear attitudes, and between political activism and nuclear activism. Internal locus of control did not correlate significantly with high sense of power or with high degree of nuclear activism.« less

A case of undeclared debt? Claude Lévi-Strauss' ambiguities and paradoxes toward analytical psychology.

PubMed

Serina, Florent

2018-06-09

If his relationship to Sigmund Freud's psychoanalysis has been widely acknowledged, Claude Lévi-Strauss' rapport with C.G. Jung's analytical psychology remains quite obscure. While secondary commentary has been abundant, its approach has above all been intertextual, to the detriment of a rigorously historical reading. Even if certain arguments put forward by supporters of so-called "influence" deserve to be taken into account, especially because they highlight Lévi-Strauss ambiguities and paradoxes toward Jung, this paper provides proof that a precise reading of the texts, with the help of recent studies on the intellectual genesis of Lévi-Strauss, lead to reject the thesis of an unstated debt owed by the French anthropologist to the Zurich psychologist. © 2018 Wiley Periodicals, Inc.

Detection and identification of Variola virus in fixed human tissue after prolonged archival storage.

PubMed

Schoepp, Randal J; Morin, Michelle D; Martinez, Mark J; Kulesh, David A; Hensley, Lisa; Geisbert, Thomas W; Brady, Daniel R; Jahrling, Peter B

2004-01-01

Smallpox disease has been eradicated from the human population since 1979, but is again a concern because of its potential use as an agent of bioterrorism or biowarfare. World Health Organization-sanctioned repositories of infectious Variola virus are known to occur in both Russia and the United States, but many believe other undeclared and unregulated sources of the virus could exist. Thus, validation of improved methods for definitive identification of smallpox virus in diagnostic specimens is urgently needed. In this paper, we describe the discovery of suspected Variola infected human tissue, fixed and preserved for decades in largely unknown solutions, and the use of routine histology, electron microscopy, and ultimately DNA extraction and fluorogenic 5' nuclease (TaqMan) assays for its identification and confirmation.

Teaching Activities on Horizontal Nuclear Proliferation.

ERIC Educational Resources Information Center

Zola, John

1990-01-01

Provides learning activities concerning the horizontal proliferation of nuclear weapons. Includes step-by-step directions for four activities: (1) the life cycle of nuclear weapons; (2) nuclear nonproliferation: pros and cons; (3) the nuclear power/nuclear weapons connection; and (4) managing nuclear proliferation. (NL)

A survey of food allergen control practices in the U.S. food industry.

PubMed

Gendel, Steven M; Khan, Nazleen; Yajnik, Monali

2013-02-01

Despite awareness of the importance of food allergy as a public health issue, recalls and adverse reactions linked to undeclared allergens in foods continue to occur with high frequency. To reduce the overall incidence of such problems and to ensure that food-allergic consumers have the information they need to prevent adverse reactions, it is important to understand which allergen control practices are currently used by the food industry. Therefore, the U.S. Food and Drug Administration carried out directed inspections of registered food facilities in 2010 to obtain a broader understanding of industry allergen control practices in the United States. The results of these inspections show that allergen awareness and the use of allergen controls have increased greatly in the last decade, but that small facilities lag in implementing allergen controls.

77 FR 70846 - Regulatory Guide 1.182, “Assessing and Managing Risk Before Maintenance Activities at Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

... Risk Before Maintenance Activities at Nuclear Power Plants'' AGENCY: Nuclear Regulatory Commission... Activities at Nuclear Power Plants,'' published in May 2000. The document is redundant due to the inclusion... Risk Before Maintenance Activities at Nuclear Power Plants,'' published in May 2000. The requirements...

Parvoviruses Cause Nuclear Envelope Breakdown by Activating Key Enzymes of Mitosis

PubMed Central

Porwal, Manvi; Cohen, Sarah; Snoussi, Kenza; Popa-Wagner, Ruth; Anderson, Fenja; Dugot-Senant, Nathalie; Wodrich, Harald; Dinsart, Christiane; Kleinschmidt, Jürgen A.; Panté, Nelly; Kann, Michael

2013-01-01

Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm and nucleus in preparatory phases. Here we used the ability of parvoviruses to induce nuclear membrane breakdown to understand the triggers of key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also upon their application to permeabilized cells. The latter technique also showed that nuclear envelope disintegration was independent upon soluble cytoplasmic factors. Using time-lapse microscopy, we observed that nuclear disassembly exhibited mitosis-like kinetics and occurred suddenly, implying a catastrophic event irrespective of cell- or type of parvovirus used. Analyzing the order of the processes allowed us to propose a model starting with direct binding of parvoviruses to distinct proteins of the nuclear pore causing structural rearrangement of the parvoviruses. The resulting exposure of domains comprising amphipathic helices was required for nuclear envelope disintegration, which comprised disruption of inner and outer nuclear membrane as shown by electron microscopy. Consistent with Ca++ efflux from the lumen between inner and outer nuclear membrane we found that Ca++ was essential for nuclear disassembly by activating PKC. PKC activation then triggered activation of cdk-2, which became further activated by caspase-3. Collectively our study shows a unique interaction of a virus with the nuclear envelope, provides evidence that a nuclear pool of executing enzymes is sufficient for nuclear disassembly in quiescent cells, and demonstrates that nuclear disassembly can be uncoupled from initial phases of mitosis. PMID:24204256

PDE4 and mAKAPβ are nodal organizers of β2-ARs nuclear PKA signaling in cardiac myocytes.

PubMed

Bedioune, Ibrahim; Lefebvre, Florence; Lechêne, Patrick; Varin, Audrey; Domergue, Valérie; Kapiloff, Michael S; Fischmeister, Rodolphe; Vandecasteele, Grégoire

2018-05-03

β1- and β2-adrenergic receptors (β-ARs) produce different acute contractile effects on the heart partly because they impact on different cytosolic pools of cAMP-dependent protein kinase (PKA). They also exert different effects on gene expression but the underlying mechanisms remain unknown. The aim of this study was to understand the mechanisms by which β1- and β2-ARs regulate nuclear PKA activity in cardiomyocytes. We used cytoplasmic and nuclear targeted biosensors to examine cAMP signals and PKA activity in adult rat ventricular myocytes upon selective β1- or β2-ARs stimulation. Both β1- and β2-AR stimulation increased cAMP and activated PKA in the cytoplasm. While the two receptors also increased cAMP in the nucleus, only β1-ARs increased nuclear PKA activity and up-regulated the PKA target gene and pro-apoptotic factor, inducible cAMP element repressor (ICER). Inhibition of PDE4, but not Gi, PDE3, GRK2 nor caveolae disruption disclosed nuclear PKA activation and ICER induction by β2-ARs. Both nuclear and cytoplasmic PKI prevented nuclear PKA activation and ICER induction by β1-ARs, indicating that PKA activation outside the nucleus is required for subsequent nuclear PKA activation and ICER mRNA expression. Cytoplasmic PKI also blocked ICER induction by β2-AR stimulation (with concomitant PDE4 inhibition). However, in this case nuclear PKI decreased ICER up-regulation by only 30%, indicating that other mechanisms are involved. Down-regulation of mAKAPβ partially inhibited nuclear PKA activation upon β1-AR stimulation, and drastically decreased nuclear PKA activation upon β2-AR stimulation in the presence of PDE4 inhibition. β1- and β2-ARs differentially regulate nuclear PKA activity and ICER expression in cardiomyocytes. PDE4 insulates a mAKAPβ-targeted PKA pool at the nuclear envelope that prevents nuclear PKA activation upon β2-AR stimulation.

Composition of Indigo naturalis.

PubMed

Plitzko, Inken; Mohn, Tobias; Sedlacek, Natalie; Hamburger, Matthias

2009-06-01

A proposal for a European Pharmacopoeia monograph concerning Indigo naturalis has recently been published, whereby the indigo (1) and indirubin (2) content should be determined by HPLC-UV. This method was tested, but problems were seen with the dosage of indigo due to poor solubility. A quantitative assay for indigo based on (1)H-NMR was developed as an alternative. The HPLC and qNMR assays were compared with eight Indigo naturalis samples. The HPLC assay consistently gave much lower indigo concentrations because solubility was the limiting factor in sample preparation. In one sample, sucrose was identified by (1)H-NMR as an organic additive. Simple wet chemistry assays for undeclared additives such as sugars and starch were tested with artificially spiked Indigo naturalis samples to establish their limits of detection, and sulfate ash determinations were carried out in view of a better assessment of Indigo naturalis in a future European monograph.

Meat Authentication via Multiple Reaction Monitoring Mass Spectrometry of Myoglobin Peptides.

PubMed

Watson, Andrew D; Gunning, Yvonne; Rigby, Neil M; Philo, Mark; Kemsley, E Kate

2015-10-20

A rapid multiple reaction monitoring (MRM) mass spectrometric method for the detection and relative quantitation of the adulteration of meat with that of an undeclared species is presented. Our approach uses corresponding proteins from the different species under investigation and corresponding peptides from those proteins, or CPCP. Selected peptide markers can be used for species detection. The use of ratios of MRM transition peak areas for corresponding peptides is proposed for relative quantitation. The approach is introduced by use of myoglobin from four meats: beef, pork, horse and lamb. Focusing in the present work on species identification, by use of predictive tools, we determine peptide markers that allow the identification of all four meats and detection of one meat added to another at levels of 1% (w/w). Candidate corresponding peptide pairs to be used for the relative quantification of one meat added to another have been observed. Preliminary quantitation data presented here are encouraging.

Authentication of Botanical Origin in Herbal Teas by Plastid Noncoding DNA Length Polymorphisms.

PubMed

Uncu, Ali Tevfik; Uncu, Ayse Ozgur; Frary, Anne; Doganlar, Sami

2015-07-01

The aim of this study was to develop a DNA barcode assay to authenticate the botanical origin of herbal teas. To reach this aim, we tested the efficiency of a PCR-capillary electrophoresis (PCR-CE) approach on commercial herbal tea samples using two noncoding plastid barcodes, the trnL intron and the intergenic spacer between trnL and trnF. Barcode DNA length polymorphisms proved successful in authenticating the species origin of herbal teas. We verified the validity of our approach by sequencing species-specific barcode amplicons from herbal tea samples. Moreover, we displayed the utility of PCR-CE assays coupled with sequencing to identify the origin of undeclared plant material in herbal tea samples. The PCR-CE assays proposed in this work can be applied as routine tests for the verification of botanical origin in herbal teas and can be extended to authenticate all types of herbal foodstuffs.

Screening and determination of sibutramine in adulterated herbal slimming supplements by HPTLC-UV densitometry.

PubMed

Mathon, Caroline; Ankli, Anita; Reich, Eike; Bieri, Stefan; Christen, Philippe

2014-01-01

The adulteration of herbal supplements is of growing importance, especially when they contain undeclared compounds like sibutramine that are unsafe drugs. Sibutramine was withdrawn from US and European markets in 2010. In this study, an HPTLC-UV densitometric method was developed for the quantification of sibutramine in herbal diet foods. Sample extracts were directly applied onto HPTLC silica gel plates and separated with a mobile phase made of a toluene-methanol mixture. Sibutramine was quantified at 225 nm and its unequivocal identification was confirmed by MS using a TLC-MS interface. During two surveys, 52 weight loss supplements obtained via the Internet were screened. Half of those were adulterated with sibutramine at amounts reaching up to 35 mg per capsule. The results of this validated HPTLC method were compared with those obtained by HPLC-UV and HPLC-MS/MS. The results were not significantly different with the three methods.

New Trends in Food Allergens Detection: Toward Biosensing Strategies.

PubMed

Alves, Rita C; Barroso, M Fátima; González-García, María Begoña; Oliveira, M Beatriz P P; Delerue-Matos, Cristina

2016-10-25

Food allergens are a real threat to sensitized individuals. Although food labeling is crucial to provide information to consumers with food allergies, accidental exposure to allergenic proteins may result from undeclared allergenic substances by means of food adulteration, fraud or uncontrolled cross-contamination. Allergens detection in foodstuffs can be a very hard task, due to their presence usually in trace amounts, together with the natural interference of the matrix. Methods for allergens analysis can be mainly divided in two large groups: the immunological assays and the DNA-based ones. Mass spectrometry has also been used as a confirmatory tool. Recently, biosensors appeared as innovative, sensitive, selective, environmentally friendly, cheaper and fast techniques (especially when automated and/or miniaturized), able to effectively replace the classical methodologies. In this review, we present the advances in the field of food allergens detection toward the biosensing strategies and discuss the challenges and future perspectives of this technology.

Halal authenticity issues in meat and meat products.

PubMed

Nakyinsige, Khadijah; Man, Yaakob Bin Che; Sazili, Awis Qurni

2012-07-01

In the recent years, Muslims have become increasingly concerned about the meat they eat. Proper product description is very crucial for consumers to make informed choices and to ensure fair trade, particularly in the ever growing halal food market. Globally, Muslim consumers are concerned about a number of issues concerning meat and meat products such as pork substitution, undeclared blood plasma, use of prohibited ingredients, pork intestine casings and non-halal methods of slaughter. Analytical techniques which are appropriate and specific have been developed to deal with particular issues. The most suitable technique for any particular sample is often determined by the nature of the sample itself. This paper sets out to identify what makes meat halal, highlight the halal authenticity issues that occur in meat and meat products and provide an overview of the possible analytical methods for halal authentication of meat and meat products. Copyright © 2012 Elsevier Ltd. All rights reserved.

Computational identification of post-translational modification-based nuclear import regulations by characterizing nuclear localization signal-import receptor interaction.

PubMed

Lin, Jhih-Rong; Liu, Zhonghao; Hu, Jianjun

2014-10-01

The binding affinity between a nuclear localization signal (NLS) and its import receptor is closely related to corresponding nuclear import activity. PTM-based modulation of the NLS binding affinity to the import receptor is one of the most understood mechanisms to regulate nuclear import of proteins. However, identification of such regulation mechanisms is challenging due to the difficulty of assessing the impact of PTM on corresponding nuclear import activities. In this study we proposed NIpredict, an effective algorithm to predict nuclear import activity given its NLS, in which molecular interaction energy components (MIECs) were used to characterize the NLS-import receptor interaction, and the support vector regression machine (SVR) was used to learn the relationship between the characterized NLS-import receptor interaction and the corresponding nuclear import activity. Our experiments showed that nuclear import activity change due to NLS change could be accurately predicted by the NIpredict algorithm. Based on NIpredict, we developed a systematic framework to identify potential PTM-based nuclear import regulations for human and yeast nuclear proteins. Application of this approach has identified the potential nuclear import regulation mechanisms by phosphorylation of two nuclear proteins including SF1 and ORC6. © 2014 Wiley Periodicals, Inc.

Stronger activation of SREBP-1a by nucleus-localized HBx

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Qi; Qiao, Ling; Yang, Jian

2015-05-08

We previously showed that hepatitis B virus (HBV) X protein activates the sterol regulatory element-binding protein-1a (SREBP-1a). Here we examined the role of nuclear localization of HBx in this process. In comparison to the wild-type and cytoplasmic HBx, nuclear HBx had stronger effects on SREBP-1a and fatty acid synthase transcription activation, intracellular lipid accumulation and cell proliferation. Furthermore, nuclear HBx could activate HBV enhancer I/X promoter and was more effective on up-regulating HBV mRNA level in the context of HBV replication than the wild-type HBx, while the cytoplasmic HBx had no effect. Our results demonstrate the functional significance of themore » nucleus-localized HBx in regulating host lipogenic pathway and HBV replication. - Highlights: • Nuclear HBx is more effective on activating SREBP-1a and FASN transcription. • Nuclear HBx is more effective on enhancing intracellular lipid accumulation. • Nuclear HBx is more effective on enhancing cell proliferation. • Nuclear HBx up-regulates HBV enhancer I/X promoter activity. • Nuclear HBx increases HBV mRNA level in the context of HBV replication.« less

STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap.

PubMed

Woroniuk, Anna; Porter, Andrew; White, Gavin; Newman, Daniel T; Diamantopoulou, Zoi; Waring, Thomas; Rooney, Claire; Strathdee, Douglas; Marston, Daniel J; Hahn, Klaus M; Sansom, Owen J; Zech, Tobias; Malliri, Angeliki

2018-05-29

The perinuclear actin cap is an important cytoskeletal structure that regulates nuclear morphology and re-orientation during front-rear polarisation. The mechanisms regulating the actin cap are currently poorly understood. Here, we demonstrate that STEF/TIAM2, a Rac1 selective guanine nucleotide exchange factor, localises at the nuclear envelope, co-localising with the key perinuclear proteins Nesprin-2G and Non-muscle myosin IIB (NMMIIB), where it regulates perinuclear Rac1 activity. We show that STEF depletion reduces apical perinuclear actin cables (a phenotype rescued by targeting active Rac1 to the nuclear envelope), increases nuclear height and impairs nuclear re-orientation. STEF down-regulation also reduces perinuclear pMLC and decreases myosin-generated tension at the nuclear envelope, suggesting that STEF-mediated Rac1 activity regulates NMMIIB activity to promote stabilisation of the perinuclear actin cap. Finally, STEF depletion decreases nuclear stiffness and reduces expression of TAZ-regulated genes, indicating an alteration in mechanosensing pathways as a consequence of disruption of the actin cap.

Activities of the DOE Nuclear Criticality Safety Program (NCSP) at the Oak Ridge Electron Linear Accelerator (ORELA)

NASA Astrophysics Data System (ADS)

Valentine, Timothy E.; Leal, Luiz C.; Guber, Klaus H.

2002-12-01

The Department of Energy established the Nuclear Criticality Safety Program (NCSP) in response to the Recommendation 97-2 by the Defense Nuclear Facilities Safety Board. The NCSP consists of seven elements of which nuclear data measurements and evaluations is a key component. The intent of the nuclear data activities is to provide high resolution nuclear data measurements that are evaluated, validated, and formatted for use by the nuclear criticality safety community to provide improved and reliable calculations for nuclear criticality safety evaluations. High resolution capture, fission, and transmission measurements are performed at the Oak Ridge Electron Linear Accelerator (ORELA) to address the needs of the criticality safety community and to address known deficiencies in nuclear data evaluations. The activities at ORELA include measurements on both light and heavy nuclei and have been used to identify improvements in measurement techniques that greatly improve the measurement of small capture cross sections. The measurement activities at ORELA provide precise and reliable high-resolution nuclear data for the nuclear criticality safety community.

Defense Threat Reduction Agency Radiochemical Needs

NASA Astrophysics Data System (ADS)

Walsh, Michael A. R.; Velazquez, Daniel L.

2009-08-01

The United States Government (USG) first developed nuclear forensics-related capabilities to analyze radiological and nuclear materials, including underground nuclear test debris and interdicted materials. Nuclear forensics is not a new mission for Department of Defense (DoD). The department's existing nuclear forensics capability is the result of programs that span six (6) decades and includes activities to assess foreign nuclear weapons testing activities, monitor and verify nuclear arms control treaties, and to support intelligence and law enforcement activities. Today, nuclear forensics must support not only weapons programs and nuclear smuggling incidents, but also the scientific analysis and subsequent attribution of terrorists' use of radiological or nuclear materials/devices. Nuclear forensics can help divulge the source of origin of nuclear materials, the type of design for an interdicted or detonated device, as well as the pathway of the materials or device to the incident. To accomplish this mission, the USG will need trained radiochemists and nuclear scientists to fill new positions and replace the retiring staff.

Age- and sex-related differences in nuclear lipid content and nucleoside triphosphatase activity in the JCR:LA-cp corpulent rat.

PubMed

Czubryt, M P; Russell, J C; Sarantopoulos, J; Gilchrist, J S; Pierce, G N

1997-11-01

The putative role of the nuclear nucleoside triphosphatase (NTPase) is to provide energy to the nuclear pore complex for poly A(+) mRNA export. Previous work has demonstrated that liver nuclear NTPase activity is greater in 6 month old corpulent (cp/cp) female JCR:LA rats, a hyperlipidemic rat model, compared to lean (+/?) animals. This increase appeared to be related to increases in nuclear membrane cholesterol content. The current study extended these initial data to compare NTPase activity as a function of age and sex in isolated JCR:LA-cp rat liver nuclei, to further test the hypothesis that nuclear membrane cholesterol may modulate NTPase activity. NTPase activity was increased in cp/cp female animals compared to +/? females at all ages studied, with Vmax values increased by 60-176%. Membrane integrity of cp/cp female nuclei was reduced compared to +/? female nuclei. Nuclear membrane cholesterol levels increased linearly with age by 50, 150 and 250% in 3, 6 and 9 month old cp/cp females over leans. In contrast, nuclei from cp/cp males exhibited only minor, isolated changes in NTPase activity. Furthermore, there were no significant changes in nuclear cholesterol content or membrane integrity in the less hyperlipidemic male animals at any age. These data suggest that altered lipid metabolism may lead to changes in nuclear membrane structure, which in turn may alter NTPase activity and functioning of the nuclear pore complex.

Identification of Gene Markers for Activation of the Nuclear Receptor Pregnane X Receptor

EPA Science Inventory

Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR in the mouse liver can lead to increases in liver weight in part through increased hepatocyte replication similar to chemicals that activate other nuclear ...

[Properties and localization of Mg- and Ca-ATpase activities in wheat embryo cell nuclei].

PubMed

Vasil'eva, N A; Belkina, G G; Stepanenko, S Y; Atalykova, F I; Oparin, A I

1978-05-01

The isolated nuclei of wheat embryo possess the ATPase activity. The addition of Mg2+ and Ca2+ significantly increases the activities of nuclear ATPases, whereas Hg2+, Cu2+ and Mn2+ inhibit the activity. The activating effect of Mg2+ is enhanced by an addition of Na and K ions. The activity of wheat embryo nuclear Mg-ATPase is higher than its Ca-ATPase activity; both ATPases also differ in their pH optima. Separation of total nuclear protein according to the solubility of its individual protein components in wheat and strong salt solutions, using the detergents, as well as ammonium sulfate precipitation and dialysis do not result in separation of Mg-activated and Ca-activated ATPases, although their levels of activities and ratios change in the course of fractionation. The Mg- and Ca-ATPase activities of the wheat embryo nuclei were found in the nuclear fraction of albumin, in nonhistone proteins and nuclear membranes. In the albumin nuclear fraction and subfractions of non-histone proteins the higher level of activity is observed in Ca-ATPase, whereas in the nuclei and soluble fractions of residual proteins in Mg-ATPase.

Bovine Lactoferrampin, Human Lactoferricin, and Lactoferrin 1-11 Inhibit Nuclear Translocation of HIV Integrase.

PubMed

Wang, Winston Yan; Wong, Jack Ho; Ip, Denis Tsz Ming; Wan, David Chi Cheong; Cheung, Randy Chifai; Ng, Tzi Bun

2016-08-01

This study aimed to investigate fragments derived from human and bovine lactoferrins for ability to inhibit nuclear translocation of HIV-1 integrase. It was shown that human lactoferricin, human lactoferrin 1-11, and bovine lactoferrampin reduced nuclear distribution of HIV-1 integrase. Bovine lactoferrampin could inhibit both the activity and nuclear translocation of HIV-1 integrase. Human lactoferrampin, bovine lactoferricin, and bovine lactoferrin 1-11 had no effect on HIV-1 integrase nuclear translocation. Human lactoferrampin which inhibited the activity of integrase did not prevent its nuclear translocation. Human lactoferricin and lactoferrin 1-11 did not inhibit HIV-1 integrase nuclear translocation despite their ability to attenuate the enzyme activity. The discrepancy between the findings on reduction of HIV-1 activity and inhibition of nuclear translocation of HIV-1 integrase was due to the different mechanisms involved. A similar reasoning can also be applied to the different inhibitory potencies of the milk peptides on different HIV enzymes, i.e., nuclear translocation.

The disavowed curriculum: understanding student's reasoning in professionally challenging situations.

PubMed

Ginsburg, Shiphra; Regehr, Glenn; Lingard, Lorelei

2003-12-01

Understanding students' perceptions of and responses to lapses in professionalism is important to shaping students' professional development. Utilize realistic, standardized professional dilemmas to obtain insight into students' reasoning and motivations in "real time." Qualitative study using 5 videotaped scenarios (each depicting a student placed in a situation which requires action in response to a professional dilemma) and individual interviews, in which students were questioned about what they would do next and why. University of Toronto. Eighteen fourth-year medical students; participation voluntary and anonymous. A model to explain students' reasoning in the face of professional dilemmas. Grounded theory analysis of interview transcripts revealed that students were motivated to consider specific actions by referencing a Principle (an abstract or idealized concept), an Affect (a feeling or emotion), or an Implication (a potential consequence of suggested actions). Principles were classified as "avowed" as ideals of our profession (e.g., honesty or disclosure), or "unavowed" (unacknowledged or undeclared, e.g., obedience or allegiance). Implications could also be avowed (e.g., concerning patients) or unavowed (e.g., concerning others); but students were predominantly motivated by considering "disavowed" implications: those pertaining to themselves (e.g., concern for grades, evaluations, or reputation), which are actively denied by the profession and discouraged as being inconsistent with altruism. This "disavowed curriculum" has implications for education, feedback, and evaluation. Instead of denying their existence, we should teach students how to negotiate and balance these unavowed and disavowed implications and principles, in order to help them develop their own professional stance.

Food control and a citizen science approach for improving teaching of Genetics in universities.

PubMed

Borrell, Y J; Muñoz-Colmenero, A M; Dopico, E; Miralles, L; Garcia-Vazquez, E

2016-09-10

A Citizen Science approach was implemented in the laboratory practices of Genetics at the University of Oviedo, related with the engaging topic of Food Control. Real samples of food products consumed by students at home (students as samplers) were employed as teaching material in three different courses of Genetics during the academic year 2014-2015: Experimental Methods in Food Production (MBTA) (Master level), and Applied Molecular Biology (BMA) and Conservation Genetics and Breeding (COMGE) (Bachelor/Degree level). Molecular genetics based on PCR amplification of DNA markers was employed for species identification of 22 seafood products in COMGE and MBTA, and for detection of genetically modified (GM) maize from nine products in BMA. In total six seafood products incorrectly labeled (27%), and two undeclared GM maize (22%) were found. A post-Laboratory survey was applied for assessing the efficacy of the approach for improving motivation in the Laboratory Practices of Genetics. Results confirmed that students that worked on their own samples from local markets were significantly more motivated and better evaluated their Genetic laboratory practices than control students (χ(2)  = 12.11 p = 0.033). Our results suggest that citizen science approaches could not be only useful for improving teaching of Genetics in universities but also to incorporate students and citizens as active agents in food control. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(5):450-462, 2016. © 2016 The International Union of Biochemistry and Molecular Biology.

Effects and Mechanisms by Which Hypercapnic Acidosis Inhibits Sepsis-Induced Canonical Nuclear Factor-κB Signaling in the Lung.

PubMed

Masterson, Claire; O'Toole, Daniel; Leo, Annemarie; McHale, Patricia; Horie, Shahd; Devaney, James; Laffey, John G

2016-04-01

Diverse effects of hypercapnic acidosis are mediated via inhibition of nuclear factor-κB, a pivotal transcription factor, in the setting of injury, inflammation, and repair, but the underlying mechanisms of action of hypercapnic acidosis on this pathway is unclear. We aim to examine the effect of hypercapnic acidosis on the nuclear factor-κB pathway in the setting of Escherichia coli-induced lung injury and characterize the underlying mechanisms in subsequent in vitro studies. In vivo animal study and subsequent in vitro studies. University Research Laboratory. Adult male Sprague-Dawley rats and pulmonary epithelial cells. Following pulmonary IκBα-SuperRepressor transgene overexpression or sham and intratracheal E. coli inoculation, rats underwent 4 hours of mechanical ventilation under normocapnia or hypercapnic acidosis, and nuclear factor-κB activation, animal survival, lung injury, and cytokine profile were assessed. Subsequent in vitro studies examined the effect of hypercapnic acidosis on specific nuclear factor-κB canonical pathway kinases via overexpression of these components and in vitro kinase activity assays. The effect of hypercapnic acidosis on the p50/p65 nuclear factor-κB heterodimer was then assessed. Hypercapnic acidosis and IκBα-SuperRepressor transgene overexpression reduced E. coli-induced lung inflammation and injury, decreased nuclear factor-κB activity, and increased animal survival. Hypercapnic acidosis inhibited canonical nuclear factor-κB signaling via reduced phosphorylative activation, reducing IκB kinase-β activation and intrinsic activity, thereby decreasing IκBα degradation, and subsequent nuclear factor-κB translocation. Hypercapnic acidosis also directly reduced DNA binding of the nuclear factor-κB p65 subunit, although this effect was less marked. Hypercapnic acidosis reduced E. coli inflammation and lung injury in vivo and reduced nuclear factor-κB activation predominantly by inhibiting the activation and intrinsic activity of IκB kinase-β.

Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration.

PubMed

Croft, Daniel R; Coleman, Mathew L; Li, Shuixing; Robertson, David; Sullivan, Teresa; Stewart, Colin L; Olson, Michael F

2005-01-17

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization.

Actin-myosin–based contraction is responsible for apoptotic nuclear disintegration

PubMed Central

Croft, Daniel R.; Coleman, Mathew L.; Li, Shuixing; Robertson, David; Sullivan, Teresa; Stewart, Colin L.; Olson, Michael F.

2005-01-01

Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization. PMID:15657395

77 FR 45697 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0149] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission. ACTION: Notice of pending U.S. Nuclear... Budget and solicitation of public comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) invites...

77 FR 29697 - Agency Information Collection Activities: Proposed Collection; Comment Request

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... NUCLEAR REGULATORY COMMISSION [NRC-2012-0066] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission. ACTION: Notice of pending U.S. Nuclear... Budget and solicitation of public comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) invites...

Safety Oversight of Decommissioning Activities at DOE Nuclear Sites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zull, Lawrence M.; Yeniscavich, William

2008-01-15

The Defense Nuclear Facilities Safety Board (Board) is an independent federal agency established by Congress in 1988 to provide nuclear safety oversight of activities at U.S. Department of Energy (DOE) defense nuclear facilities. The activities under the Board's jurisdiction include the design, construction, startup, operation, and decommissioning of defense nuclear facilities at DOE sites. This paper reviews the Board's safety oversight of decommissioning activities at DOE sites, identifies the safety problems observed, and discusses Board initiatives to improve the safety of decommissioning activities at DOE sites. The decommissioning of former defense nuclear facilities has reduced the risk of radioactive materialmore » contamination and exposure to the public and site workers. In general, efforts to perform decommissioning work at DOE defense nuclear sites have been successful, and contractors performing decommissioning work have a good safety record. Decommissioning activities have recently been completed at sites identified for closure, including the Rocky Flats Environmental Technology Site, the Fernald Closure Project, and the Miamisburg Closure Project (the Mound site). The Rocky Flats and Fernald sites, which produced plutonium parts and uranium materials for defense needs (respectively), have been turned into wildlife refuges. The Mound site, which performed R and D activities on nuclear materials, has been converted into an industrial and technology park called the Mound Advanced Technology Center. The DOE Office of Legacy Management is responsible for the long term stewardship of these former EM sites. The Board has reviewed many decommissioning activities, and noted that there are valuable lessons learned that can benefit both DOE and the contractor. As part of its ongoing safety oversight responsibilities, the Board and its staff will continue to review the safety of DOE and contractor decommissioning activities at DOE defense nuclear sites.« less

The US nuclear reaction data network. Summary of the first meeting, March 13 & 14 1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-03-01

The first meeting of the US Nuclear Reaction Data Network (USNRDN) was held at the Colorado School of Mines, March 13-14, 1996 chaired by F. Edward Cecil. The Agenda of the meeting is attached. The Network, its mission, products and services; related nuclear data and data networks, members, and organization are described in Attachment 1. The following progress reports from the members of the USNRDN were distributed prior to the meeting and are given as Attachment 2. (1) Measurements and Development of Analytic Techniques for Basic Nuclear Physics and Nuclear Applications; (2) Nuclear Reaction Data Activities at the National Nuclearmore » Data Center; (3) Studies of nuclear reactions at very low energies; (4) Nuclear Reaction Data Activities, Nuclear Data Group; (5) Progress in Neutron Physics at Los Alamos - Experiments; (6) Nuclear Reaction Data Activities in Group T2; (7) Progress Report for the US Nuclear Reaction Data Network Meeting; (8) Nuclear Astrophysics Research Group (ORNL); (9) Progress Report from Ohio University; (10) Exciton Model Phenomenology; and (11) Progress Report for Coordination Meeting USNRDN.« less

Geospatial Image Mining For Nuclear Proliferation Detection: Challenges and New Opportunities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vatsavai, Raju; Bhaduri, Budhendra L; Cheriyadat, Anil M

2010-01-01

With increasing understanding and availability of nuclear technologies, and increasing persuasion of nuclear technologies by several new countries, it is increasingly becoming important to monitor the nuclear proliferation activities. There is a great need for developing technologies to automatically or semi-automatically detect nuclear proliferation activities using remote sensing. Images acquired from earth observation satellites is an important source of information in detecting proliferation activities. High-resolution remote sensing images are highly useful in verifying the correctness, as well as completeness of any nuclear program. DOE national laboratories are interested in detecting nuclear proliferation by developing advanced geospatial image mining algorithms. Inmore » this paper we describe the current understanding of geospatial image mining techniques and enumerate key gaps and identify future research needs in the context of nuclear proliferation.« less

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation.

PubMed

Bonnet, Amandine; Randrianarison-Huetz, Voahangy; Nzounza, Patrycja; Nedelec, Martine; Chazal, Maxime; Waast, Laetitia; Pene, Sabrina; Bazarbachi, Ali; Mahieux, Renaud; Bénit, Laurence; Pique, Claudine

2012-09-25

The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4⁺ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4⁺ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. These data reveal that the formation of Tax nuclear bodies, previously associated to transcriptional activities in Tax-transfected cells, is dispensable for NF-κB promoter activation, notably in CD4⁺ T cells. They also provide the first evidence that Tax SUMOylation is not a key determinant for Tax-induced NF-κB activation.

Low nuclear body formation and tax SUMOylation do not prevent NF-kappaB promoter activation

PubMed Central

2012-01-01

Background The Tax protein encoded by Human T-lymphotropic virus type 1 (HTLV-1) is a powerful activator of the NF-κB pathway, a property critical for HTLV-1-induced immortalization of CD4+ T lymphocytes. Tax permanently stimulates this pathway at a cytoplasmic level by activating the IκB kinase (IKK) complex and at a nuclear level by enhancing the binding of the NF-κB factor RelA to its cognate promoters and by forming nuclear bodies, believed to represent transcriptionally active structures. In previous studies, we reported that Tax ubiquitination and SUMOylation play a critical role in Tax localization and NF-κB activation. Indeed, analysis of lysine Tax mutants fused or not to ubiquitin or SUMO led us to propose a two-step model in which Tax ubiquitination first intervenes to activate IKK while Tax SUMOylation is subsequently required for promoter activation within Tax nuclear bodies. However, recent studies showing that ubiquitin or SUMO can modulate Tax activities in either the nucleus or the cytoplasm and that SUMOylated Tax can serve as substrate for ubiquitination suggested that Tax ubiquitination and SUMOylation may mediate redundant rather than successive functions. Results In this study, we analyzed the properties of a new Tax mutant that is properly ubiquitinated, but defective for both nuclear body formation and SUMOylation. We report that reducing Tax SUMOylation and nuclear body formation do not alter the ability of Tax to activate IKK, induce RelA nuclear translocation, and trigger gene expression from a NF-κB promoter. Importantly, potent NF-κB promoter activation by Tax despite low SUMOylation and nuclear body formation is also observed in T cells, including CD4+ primary T lymphocytes. Moreover, we show that Tax nuclear bodies are hardly observed in HTLV-1-infected T cells. Finally, we provide direct evidence that the degree of NF-κB activation by Tax correlates with the level of Tax ubiquitination, but not SUMOylation. Conclusions These data reveal that the formation of Tax nuclear bodies, previously associated to transcriptional activities in Tax-transfected cells, is dispensable for NF-κB promoter activation, notably in CD4+ T cells. They also provide the first evidence that Tax SUMOylation is not a key determinant for Tax-induced NF-κB activation. PMID:23009398

Working Party on International Nuclear Data Evaluation Cooperation (WPEC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dupont, E., E-mail: wpec@oecd-nea.org; Chadwick, M.B.; Danon, Y.

The OECD Nuclear Energy Agency (NEA) organizes cooperation between the major nuclear data evaluation projects in the world. The NEA Working Party on International Nuclear Data Evaluation Cooperation (WPEC) was established to promote the exchange of information on nuclear data evaluation, measurement, nuclear model calculation, validation, and related topics, and to provide a framework for cooperative activities between the participating projects. The working party assesses nuclear data improvement needs and addresses these needs by initiating joint activities in the framework of dedicated WPEC subgroups. Studies recently completed comprise a number of works related to nuclear data covariance and associated processingmore » issues, as well as more specific studies related to the resonance parameter representation in the unresolved resonance region, the gamma production from fission product capture reactions, the {sup 235}U capture cross section, the EXFOR database, and the improvement of nuclear data for advanced reactor systems. Ongoing activities focus on the evaluation of {sup 239}Pu in the resonance region, scattering angular distribution in the fast energy range, and reporting/usage of experimental data for evaluation in the resolved resonance region. New activities include two subgroups on improved fission product yield evaluation methodologies and on modern nuclear database structures. Future activities under discussion include a pilot project for a Collaborative International Evaluated Library Organization (CIELO) and methods to provide feedback from nuclear and covariance data adjustment for improvement of nuclear data. In addition to the above mentioned short-term task-oriented subgroups, WPEC also hosts a longer-term subgroup charged with reviewing and compiling the most important nuclear data requirements in a high priority request list (HPRL)« less

Working Party on International Nuclear Data Evaluation Cooperation (WPEC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giuseppe Palmiotti

The OECD Nuclear Energy Agency (NEA) is organizing the cooperation between the major nuclear data evaluation projects in the world. The NEA Working Party on International Nuclear Data Evaluation Cooperation (WPEC) was established to promote the exchange of information on nuclear data evaluation, measurement, nuclear model calculation, validation, and related topics, and to provide a framework for cooperative activities between the participating projects. The working party assesses nuclear data improvement needs and addresses these needs by initiating joint activities in the framework of dedicated WPEC subgroups. Studies recently completed comprise a number of works related to nuclear data covariance andmore » associated processing issues, as well as more specific studies related to the resonance parameter representation in the unresolved resonance region, the gamma production from fission-product capture reactions, the U-235 capture cross-section, the EXFOR database, and the improvement of nuclear data for advanced reactor systems. Ongoing activities focus on the evaluation of Pu-239 in the resonance region, scattering angular distribution in the fast energy range, and reporting/usage of experimental data for evaluation in the resolved resonance region. New activities include two new subgroups on improved fission product yield evaluation methodologies and on modern nuclear database structures. Future activities under discussion include a pilot project of a Collaborative International Evaluated Library (CIELO) and methods to provide feedback from nuclear and covariance data adjustment for improvement of nuclear data. In addition to the above mentioned short-term, task-oriented subgroups, the WPEC also hosts a longer-term subgroup charged with reviewing and compiling the most important nuclear data requirements in a high priority request list (HPRL).« less

Working Party on International Nuclear Data Evaluation Cooperation (WPEC)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dupont, E.; Herman, M.; Dupont, E.

The OECD Nuclear Energy Agency (NEA) organizes cooperation between the major nuclear data evaluation projects in the world. Moreover, the NEA Working Party on International Nuclear Data Evaluation Cooperation (WPEC) was established to promote the exchange of information on nuclear data evaluation, measurement, nuclear model calculation, validation, and related topics, and to provide a framework for cooperative activities between the participating projects. The working party assesses nuclear data improvement needs and addresses these needs by initiating joint activities in the framework of dedicated WPEC subgroups. Studies recently completed comprise a number of works related to nuclear data covariance and associatedmore » processing issues, as well as more specific studies related to the resonance parameter representation in the unresolved resonance region, the gamma production from fission product capture reactions, the 235U capture cross section, the EXFOR database, and the improvement of nuclear data for advanced reactor systems. Ongoing activities focus on the evaluation of 239Pu in the resonance region, scattering angular distribution in the fast energy range, and reporting/usage of experimental data for evaluation in the resolved resonance region. New activities include two subgroups on improved fission product yield evaluation methodologies and on modern nuclear database structures. Some future activities under discussion include a pilot project for a Collaborative International Evaluated Library Organization (CIELO) and methods to provide feedback from nuclear and covariance data adjustment for improvement of nuclear data. In addition to the above mentioned short-term task-oriented subgroups, WPEC also hosts a longer-term subgroup charged with reviewing and compiling the most important nuclear data requirements in a high priority request list (HPRL).« less

Emerin and histone deacetylase 3 (HDAC3) cooperatively regulate expression and nuclear positions of MyoD, Myf5, and Pax7 genes during myogenesis

PubMed Central

Demmerle, Justin; Koch, Adam J.; Holaska, James M.

2016-01-01

The spatial organization of chromatin is critical in establishing cell-type dependent gene expression programs. The inner nuclear membrane protein emerin has been implicated in regulating global chromatin architecture. We show emerin associates with genomic loci of muscle differentiation promoting factors in murine myogenic progenitors, including Myf5 and MyoD. Prior to their transcriptional activation Myf5 and MyoD loci localized to the nuclear lamina in proliferating progenitors and moved to the nucleoplasm upon transcriptional activation during differentiation. The Pax7 locus, which is transcribed in proliferating progenitors, localized to the nucleoplasm and Pax7 moved to the nuclear lamina upon repression during differentiation. Localization of Myf5, MyoD, and Pax7 to the nuclear lamina and proper temporal expression of these genes required emerin and HDAC3. Interestingly, activation of HDAC3 catalytic activity rescued both Myf5 localization to the nuclear lamina and its expression. Collectively, these data support a model whereby emerin facilitates repressive chromatin formation at the nuclear lamina by activating the catalytic activity of HDAC3 to regulate the coordinated spatiotemporal expression of myogenic differentiation genes. PMID:24062260

Chromatographic fingerprinting through chemometric techniques for herbal slimming pills: A way of adulterant identification.

PubMed

Shekari, Nafiseh; Vosough, Maryam; Tabar Heidar, Kourosh

2018-05-01

In the current study, gas chromatography-mass spectrometry (GC-MS) fingerprinting of herbal slimming pills assisted by chemometric methods has been presented. Deconvolution of two-way chromatographic signals of nine herbal slimming pills into pure chromatographic and spectral patterns was performed. The peak clusters were resolved using multivariate curve resolution-alternating least squares (MCR-ALS) by employing appropriate constraints. It was revealed that more useful chemical information about the composition of the slimming pills can be obtained by employing sophisticated GC-MS method coupled with proper chemometric tools yielding the extended number of identified constituents. The thorough fingerprinting of the complex mixtures proved the presence of some toxic or carcinogen components, such as toluene, furfural, furfuryl alcohol, styrene, itaconic anhydride, citraconic anhydride, trimethyl phosphate, phenol, pyrocatechol, p-propenylanisole and pyrogallol. In addition, some samples were shown to be adulterated with undeclared ingredients, including stimulants, anorexiant and laxatives such as phenolphthalein, amfepramone, caffeine and sibutramine. Copyright © 2018 Elsevier B.V. All rights reserved.

Method for the isolation of citric acid and malic acid in Japanese apricot liqueur for carbon stable isotope analysis.

PubMed

Akamatsu, Fumikazu; Hashiguchi, Tomokazu; Hisatsune, Yuri; Oe, Takaaki; Kawao, Takafumi; Fujii, Tsutomu

2017-02-15

A method for detecting the undeclared addition of acidic ingredients is required to control the authenticity of Japanese apricot liqueur. We developed an analytical procedure that minimizes carbon isotope discrimination for measurement of the δ(13)C values of citric and malic acid isolated from Japanese apricot liqueur. Our results demonstrated that freeze-drying is preferable to nitrogen spray-drying, because it does not significantly affect the δ(13)C values of citric acid and results in smaller isotope discrimination for malic acid. Both 0.1% formic acid and 0.2% phosphoric acid are acceptable HPLC mobile phases for the isolation of citric and malic acid, although the δ(13)C values of malic acid exhibited relatively large variation compared with citric acid following isolation using either mobile phase. The developed procedure allows precise δ(13)C measurements of citric and malic acid isolated from Japanese apricot liqueur. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of diffusion-ordered NMR spectroscopy and HPLC-UV-SPE-NMR to identify undeclared synthetic drugs in medicines illegally sold as phytotherapies.

PubMed

Silva, Lorena M A; Filho, Elenilson G A; Thomasi, Sérgio S; Silva, Bianca F; Ferreira, Antonio G; Venâncio, Tiago

2013-09-01

The informal (and/or illegal) e-commerce of pharmaceutical formulations causes problems that governmental health agencies find hard to control, one of which concerns formulas sold as natural products. The purpose of this work was to explore the advantages and limitations of DOSY and HPLC-UV-SPE-NMR. These techniques were used to identify the components of a formula illegally marketed in Brazil as an herbal medicine possessing anti-inflammatory and analgesic properties. DOSY was able to detect the major components present at higher concentrations. Complete characterization was achieved using HPLC-UV-SPE-NMR, and 1D and 2D NMR analyses enabled the identification of known synthetic drugs. These were ranitidine and a mixture of orphenadrine citrate, piroxicam, and dexamethasone, which are co-formulated in a remedy called Rheumazim that is used to relieve severe pain, but it is prohibited in Brazil because of a lack of sufficient pharmacokinetic and pharmacodynamic information. Copyright © 2013 John Wiley & Sons, Ltd.

The nuclear lamina and heterochromatin: a complex relationship.

PubMed

Bank, Erin M; Gruenbaum, Yosef

2011-12-01

In metazoan cells, the heterochromatin is generally localized at the nuclear periphery, whereas active genes are preferentially found in the nuclear interior. In the present paper, we review current evidence showing that components of the nuclear lamina interact directly with heterochromatin, which implicates the nuclear lamina in a mechanism of specific gene retention at the nuclear periphery and release to the nuclear interior upon gene activation. We also discuss recent data showing that mutations in lamin proteins affect gene positioning and expression, providing a potential mechanism for how these mutations lead to tissue-specific diseases.

75 FR 39056 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-07

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0113] Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB) Review; Comment Request AGENCY: U.S. Nuclear Regulatory... byproduct, source, or special nuclear material that are ceasing licensed activities and terminating the...

Fluorescent recovery after photobleaching (FRAP) analysis of nuclear export rates identifies intrinsic features of nucleocytoplasmic transport.

PubMed

Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

2012-02-17

A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level.

Occupational Employment in Nuclear-Related Activities, 1981.

ERIC Educational Resources Information Center

Baker, Joe G.; Olsen, Kathryn

Employment in nuclear- and nuclear energy-related activities in 1981 was examined and compared to that in previous years. Survey instruments were returned by 784 establishments. Total 1981 nuclear-related employment was estimated to be 249,500--a growth of 22,600 (10%) workers over the 1977 total. Government-owned, contractor-operated (GOCO)…

The US Nuclear Data Network

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-10-19

This report discusses the following topics: US Nuclear Data Network Meeting; TUNL A=3--20 Data Project Activity Report 1993; INEL Mass-chain Evaluation Project Activity Report for 1993; 1993 Isotopes; Nuclear Data Project Activity Report; The NNDC Activity Report Parts A and B; Minutes of the Formats and Procedures Subcommittee; Evaluation of High-spin Nuclear Data for ENSDF and Table of Superdeformed Nuclear Bands; Proposal for Support of a Experimental High-spin; Data File/Data-Network Coordinator; Radioactive Decay and Applications; A Plan for a Horizontal Evaluation of Decay Data; ENSDF On-line System; The MacNuclide Project Expanding the Scope of the Nuclear Structure Reference File; ENSDAT:more » Evaluated Nuclear Structure Drawings and Tables; Cross Section Evaluation Working Group (CSEWG) and CSEWG Strategy Session; A Draft Proposal for a USNDN Program Advisory Council; Recommendations of Focus Group 1; Recommendations of Focus Group 2; Recommendations of Focus Group 3; Recommendations of Focus Group 4; The Table of Isotopes; The Isotopes CD-ROM; Electronic Table of Isotopes (ETOI); and Electronic Access to Nuclear Data.« less

Dynamics and Function of Nuclear Bodies during Embryogenesis.

PubMed

Arias Escayola, Dahyana; Neugebauer, Karla M

2018-05-01

Nuclear bodies are RNA-rich membraneless organelles in the cell nucleus that concentrate specific sets of nuclear proteins and RNA-protein complexes. Nuclear bodies such as the nucleolus, Cajal body (CB), and the histone locus body (HLB) concentrate factors required for nuclear steps of RNA processing. Formation of these nuclear bodies occurs on genomic loci and is frequently associated with active sites of transcription. Whether nuclear body formation is dependent on a particular gene element, an active process such as transcription, or the nascent RNA present at gene loci is a topic of debate. Recently, this question has been addressed through studies in model organisms and their embryos. The switch from maternally provided RNA and protein to zygotic gene products in early embryos has been well characterized in a variety of organisms. This process, termed maternal-to-zygotic transition, provides an excellent model for studying formation of nuclear bodies before, during, and after the transcriptional activation of the zygotic genome. Here, we review findings in embryos that reveal key principles in the study of the formation and function of nucleoli, CBs, and HLBs. We propose that while particular gene elements may contribute to formation of these nuclear bodies, active transcription promotes maturation of nuclear bodies and efficient RNA processing within them.

Role of regulatory subunits and protein kinase inhibitor (PKI) in determining nuclear localization and activity of the catalytic subunit of protein kinase A.

PubMed

Wiley, J C; Wailes, L A; Idzerda, R L; McKnight, G S

1999-03-05

Regulation of protein kinase A by subcellular localization may be critical to target catalytic subunits to specific substrates. We employed epitope-tagged catalytic subunit to correlate subcellular localization and gene-inducing activity in the presence of regulatory subunit or protein kinase inhibitor (PKI). Transiently expressed catalytic subunit distributed throughout the cell and induced gene expression. Co-expression of regulatory subunit or PKI blocked gene induction and prevented nuclear accumulation. A mutant PKI lacking the nuclear export signal blocked gene induction but not nuclear accumulation, demonstrating that nuclear export is not essential to inhibit gene induction. When the catalytic subunit was targeted to the nucleus with a nuclear localization signal, it was not sequestered in the cytoplasm by regulatory subunit, although its activity was completely inhibited. PKI redistributed the nuclear catalytic subunit to the cytoplasm and blocked gene induction, demonstrating that the nuclear export signal of PKI can override a strong nuclear localization signal. With increasing PKI, the export process appeared to saturate, resulting in the return of catalytic subunit to the nucleus. These results demonstrate that both the regulatory subunit and PKI are able to completely inhibit the gene-inducing activity of the catalytic subunit even when the catalytic subunit is forced to concentrate in the nuclear compartment.

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

PubMed Central

Albi, Elisabetta; Perrella, Giuseppina; Lazzarini, Andrea; Cataldi, Samuela; Lazzarini, Remo; Floridi, Alessandro; Ambesi-Impiombato, Francesco Saverio; Curcio, Francesco

2014-01-01

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein. PMID:24979136

A Program for Cultivating Nuclear Talent at Engineering Educational Institute in a Remote Area from Nuclear Power Plants

NASA Astrophysics Data System (ADS)

Takahashi, Tsuyoshi

Recently, in Japan, the number of students who hope for finding employment at the nuclear power company has decreased as students‧ concern for the nuclear power industry decreases. To improve the situation, Ministry of Education, Culture, Sports, Science and Technology launched the program of cultivating talent for nuclear power which supports research and education of nuclear power in the academic year of 2007. Supported by the program, Kushiro College of Technology conducted several activities concerning nuclear power for about a year. The students came to be interested in nuclear engineering through these activities and its results.

15 CFR 783.4 - Deadlines for submission of reports and amendments.

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATIONS CIVIL NUCLEAR FUEL CYCLE-RELATED ACTIVITIES NOT INVOLVING NUCLEAR MATERIALS § 783.4 Deadlines for... location that commenced one or more of the civil nuclear fuel cycle-related activities described in § 783.1... activities involving uranium hard-rock mines must include any such mines that were closed down during...

15 CFR 783.4 - Deadlines for submission of reports and amendments.

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS CIVIL NUCLEAR FUEL CYCLE-RELATED ACTIVITIES NOT INVOLVING NUCLEAR MATERIALS § 783.4 Deadlines for... location that commenced one or more of the civil nuclear fuel cycle-related activities described in § 783.1... activities involving uranium hard-rock mines must include any such mines that were closed down during...

15 CFR 783.4 - Deadlines for submission of reports and amendments.

Code of Federal Regulations, 2012 CFR

2012-01-01

... REGULATIONS CIVIL NUCLEAR FUEL CYCLE-RELATED ACTIVITIES NOT INVOLVING NUCLEAR MATERIALS § 783.4 Deadlines for... location that commenced one or more of the civil nuclear fuel cycle-related activities described in § 783.1... activities involving uranium hard-rock mines must include any such mines that were closed down during...

15 CFR 783.4 - Deadlines for submission of reports and amendments.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS CIVIL NUCLEAR FUEL CYCLE-RELATED ACTIVITIES NOT INVOLVING NUCLEAR MATERIALS § 783.4 Deadlines for... location that commenced one or more of the civil nuclear fuel cycle-related activities described in § 783.1... activities involving uranium hard-rock mines must include any such mines that were closed down during...

15 CFR 783.4 - Deadlines for submission of reports and amendments.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATIONS CIVIL NUCLEAR FUEL CYCLE-RELATED ACTIVITIES NOT INVOLVING NUCLEAR MATERIALS § 783.4 Deadlines for... location that commenced one or more of the civil nuclear fuel cycle-related activities described in § 783.1... activities involving uranium hard-rock mines must include any such mines that were closed down during...

Galaxy interactions and the stimulation of nuclear activity

NASA Technical Reports Server (NTRS)

Heckman, Timothy M.

1990-01-01

The author discusses the idea that interactions between galaxies can lead to enhanced galactic activity. He discusses whether, apart from the observational evidence, there is a strong theoretical or heuristic motivation for investigating galaxy interactions as stimulators of nuclear activity in galaxies. Galactic interactions as mechanisms for triggering nuclear starbursts are covered.

Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner*

PubMed Central

Hughes, Maria L. R.; Liu, Bonan; Halls, Michelle L.; Wagstaff, Kylie M.; Patil, Rahul; Velkov, Tony; Jans, David A.; Bunnett, Nigel W.; Scanlon, Martin J.; Porter, Christopher J. H.

2015-01-01

Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fatty acid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner. PMID:25847235

Fatty Acid-binding Proteins 1 and 2 Differentially Modulate the Activation of Peroxisome Proliferator-activated Receptor α in a Ligand-selective Manner.

PubMed

Hughes, Maria L R; Liu, Bonan; Halls, Michelle L; Wagstaff, Kylie M; Patil, Rahul; Velkov, Tony; Jans, David A; Bunnett, Nigel W; Scanlon, Martin J; Porter, Christopher J H

2015-05-29

Nuclear hormone receptors (NHRs) regulate the expression of proteins that control aspects of reproduction, development and metabolism, and are major therapeutic targets. However, NHRs are ubiquitous and participate in multiple physiological processes. Drugs that act at NHRs are therefore commonly restricted by toxicity, often at nontarget organs. For endogenous NHR ligands, intracellular lipid-binding proteins, including the fatty acid-binding proteins (FABPs), can chaperone ligands to the nucleus and promote NHR activation. Drugs also bind FABPs, raising the possibility that FABPs similarly regulate drug activity at the NHRs. Here, we investigate the ability of FABP1 and FABP2 (intracellular lipid-binding proteins that are highly expressed in tissues involved in lipid metabolism, including the liver and intestine) to influence drug-mediated activation of the lipid regulator peroxisome proliferator-activated receptor (PPAR) α. We show by quantitative fluorescence imaging and gene reporter assays that drug binding to FABP1 and FABP2 promotes nuclear localization and PPARα activation in a drug- and FABP-dependent manner. We further show that nuclear accumulation of FABP1 and FABP2 is dependent on the presence of PPARα. Nuclear accumulation of FABP on drug binding is driven largely by reduced nuclear egress rather than an increased rate of nuclear entry. Importin binding assays indicate that nuclear access occurs via an importin-independent mechanism. Together, the data suggest that specific drug-FABP complexes can interact with PPARα to effect nuclear accumulation of FABP and NHR activation. Because FABPs are expressed in a regionally selective manner, this may provide a means to tailor the patterns of NHR drug activation in a tissue-specific manner. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Fluorescent Recovery after Photobleaching (FRAP) Analysis of Nuclear Export Rates Identifies Intrinsic Features of Nucleocytoplasmic Transport*

PubMed Central

Cardarelli, Francesco; Tosti, Luca; Serresi, Michela; Beltram, Fabio; Bizzarri, Ranieri

2012-01-01

A quantitative description of carrier-mediated nuclear export in live cells is presented. To this end, we fused a prototypical leucine-rich nuclear export signal (NES) to GFP as a cargo model and expressed the fluorescent chimera in live CHO-K1 cells. By modeling FRAP data, we calculate the NES affinity for the export machinery and the maximum rate of nuclear export achievable at saturation of endogenous carriers. The measured active-export time through the Nuclear Pore Complex (NPC) is 18 ms, remarkably similar to the previously determined active-import rate. Also, our results reveal that active export/import and active export/passive diffusion fluxes are uncoupled, thus complementing previous reports on active import/passive diffusion uncoupling. These findings suggest differential gating at the NPC level. PMID:22190681

Neural net controlled tag gas sampling system for nuclear reactors

DOEpatents

Gross, Kenneth C.; Laug, Matthew T.; Lambert, John D. B.; Herzog, James P.

1997-01-01

A method and system for providing a tag gas identifier to a nuclear fuel rod and analyze escaped tag gas to identify a particular failed nuclear fuel rod. The method and system include disposing a unique tag gas composition into a plenum of a nuclear fuel rod, monitoring gamma ray activity, analyzing gamma ray signals to assess whether a nuclear fuel rod has failed and is emitting tag gas, activating a tag gas sampling and analysis system upon sensing tag gas emission from a failed nuclear rod and evaluating the escaped tag gas to identify the particular failed nuclear fuel rod.

Components of the CCR4-NOT complex function as nuclear hormone receptor coactivators via association with the NRC-interacting Factor NIF-1.

PubMed

Garapaty, Shivani; Mahajan, Muktar A; Samuels, Herbert H

2008-03-14

CCR4-NOT is an evolutionarily conserved, multicomponent complex known to be involved in transcription as well as mRNA degradation. Various subunits (e.g. CNOT1 and CNOT7/CAF1) have been reported to be involved in influencing nuclear hormone receptor activities. Here, we show that CCR4/CNOT6 and RCD1/CNOT9, members of the CCR4-NOT complex, potentiate nuclear receptor activity. RCD1 interacts in vivo and in vitro with NIF-1 (NRC-interacting factor), a previously characterized nuclear receptor cotransducer that activates nuclear receptors via its interaction with NRC. As with NIF-1, RCD1 and CCR4 do not directly associate with nuclear receptors; however, they enhance ligand-dependent transcriptional activation by nuclear hormone receptors. CCR4 mediates its effect through the ligand binding domain of nuclear receptors and small interference RNA-mediated silencing of endogenous CCR4 results in a marked decrease in nuclear receptor activation. Furthermore, knockdown of CCR4 results in an attenuated stimulation of RARalpha target genes (e.g. Sox9 and HoxA1) as shown by quantitative PCR assays. The silencing of endogenous NIF-1 also resulted in a comparable decrease in the RAR-mediated induction of both Sox9 and HoxA1. Furthermore, CCR4 associates in vivo with NIF-1. In addition, the CCR4-enhanced transcriptional activation by nuclear receptors is dependent on NIF-1. The small interference RNA-mediated knockdown of NIF-1 blocks the ligand-dependent potentiating effect of CCR4. Our results suggest that CCR4 plays a role in the regulation of certain endogenous RARalpha target genes and that RCD1 and CCR4 might mediate their function through their interaction with NIF-1.

Propagation of nuclear data uncertainties for fusion power measurements

NASA Astrophysics Data System (ADS)

Sjöstrand, Henrik; Conroy, Sean; Helgesson, Petter; Hernandez, Solis Augusto; Koning, Arjan; Pomp, Stephan; Rochman, Dimitri

2017-09-01

Neutron measurements using neutron activation systems are an essential part of the diagnostic system at large fusion machines such as JET and ITER. Nuclear data is used to infer the neutron yield. Consequently, high-quality nuclear data is essential for the proper determination of the neutron yield and fusion power. However, uncertainties due to nuclear data are not fully taken into account in uncertainty analysis for neutron yield calibrations using activation foils. This paper investigates the neutron yield uncertainty due to nuclear data using the so-called Total Monte Carlo Method. The work is performed using a detailed MCNP model of the JET fusion machine; the uncertainties due to the cross-sections and angular distributions in JET structural materials, as well as the activation cross-sections in the activation foils, are analysed. It is found that a significant contribution to the neutron yield uncertainty can come from uncertainties in the nuclear data.

Integral isolation valve systems for loss of coolant accident protection

DOEpatents

Kanuch, David J.; DiFilipo, Paul P.

2018-03-20

A nuclear reactor includes a nuclear reactor core comprising fissile material disposed in a reactor pressure vessel having vessel penetrations that exclusively carry flow into the nuclear reactor and at least one vessel penetration that carries flow out of the nuclear reactor. An integral isolation valve (IIV) system includes passive IIVs each comprising a check valve built into a forged flange and not including an actuator, and one or more active IIVs each comprising an active valve built into a forged flange and including an actuator. Each vessel penetration exclusively carrying flow into the nuclear reactor is protected by a passive IIV whose forged flange is directly connected to the vessel penetration. Each vessel penetration carrying flow out of the nuclear reactor is protected by an active IIV whose forged flange is directly connected to the vessel penetration. Each active valve may be a normally closed valve.

Crosstalk between ERK2 and RXR regulates nuclear import of transcription factor NGFI-B

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacobs, Chris M.; Paulsen, Ragnhild E.

2005-10-21

Transcription factor NGFI-B initiates apoptosis when allowed to translocate to mitochondria. Retinoid-X receptor (RXR), another member of the nuclear receptor family, regulates NGFI-B signaling through heterodimerization and nuclear export. Growth factor EGF activates ERK2, which phosphorylates NGFI-B and determines if NGFI-B is allowed to translocate to mitochondria. In the present study, EGF treatment resulted in an increased nuclear import of NGFI-B. Likewise, active ERK2 resulted in a preferential nuclear localization of NGFI-B. When coexpressed with RXR the nuclear import and nuclear localization induced by active ERK2 were strongly reduced. In the presence of its ligand 9-cis-retinoic acid, RXR no longermore » inhibited ERK2-induced nuclear import. Thus, RXR serves a permissive role for ERK2-mediated nuclear accumulation of NGFI-B. This finding represents a novel crosstalk between ERK2 and RXR signaling pathways, and explains how two independent inhibitors of apoptosis (EGF and 9-cis-retinoic acid) may cooperate to regulate nuclear targeting of apoptosis inducer NGFI-B.« less

On Line Enrichment Monitor (OLEM) UF 6 Tests for 1.5" Sch40 SS Pipe, Revision 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

March-Leuba, José A.; Garner, Jim; Younkin, Jim

As global uranium enrichment capacity under international safeguards expands, the International Atomic Energy Agency (IAEA) is challenged to develop effective safeguards approaches at gaseous centrifuge enrichment plants while working within budgetary constraints. The “Model Safeguards Approach for Gas Centrifuge Enrichment Plants” (GCEPs) developed by the IAEA Division of Concepts and Planning in June 2006, defines the three primary Safeguards objectives to be the timely detection of: 1) diversion of significant quantities of natural (NU), depleted (DU) or low-enriched uranium (LEU) from declared plant flow, 2) facility misuse to produce undeclared LEU product from undeclared feed, and 3) facility misuse tomore » produce enrichments higher than the declared maximum, in particular, highly enriched uranium (HEU). The ability to continuously and independently (i.e. with a minimum of information from the facility operator) monitor not only the uranium mass balance but also the 235U mass balance in the facility could help support all three verification objectives described above. Two key capabilities required to achieve an independent and accurate material balance are 1) continuous, unattended monitoring of in-process UF 6 and 2) monitoring of cylinders entering and leaving the facility. The continuous monitoring of in-process UF 6 would rely on a combination of load-cell monitoring of the cylinders at the feed and withdrawal stations, online monitoring of gas enrichment, and a high-accuracy net weight measurement of the cylinder contents. The Online Enrichment Monitor (OLEM) is the instrument that would continuously measure the time-dependent relative uranium enrichment, E(t), in weight percent 235U, of the gas filling or being withdrawn from the cylinders. The OLEM design concept combines gamma-ray spectrometry using a collimated NaI(Tl) detector with gas pressure and temperature data to calculate the enrichment of the UF 6 gas within the unit header pipe as a function of time. The OLEM components have been tested on ORNL UF 6 flow loop. Data were collected at five different enrichment levels (0.71%, 2.97%, 4.62%, 6.0%, and 93.7%) at several pressure conditions. The test data were collected in the standard OLEM N.4242 file format for each of the conditions with a 10-minute sampling period and then averaged over the span of constant pressures. Analysis of the collected data has provided enrichment constants that can be used for 1.5” stainless steel schedule 40 pipe measurement sites. The enrichment constant is consistent among all the wide range of enrichment levels and pressures used.« less

78 FR 13712 - U.S. Nuclear Regulatory Commission Planned Monitoring Activities for F-Area Tank Farm at the...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-28

... Monitoring Activities for F-Area Tank Farm at the Savannah River Site, Revision 0 AGENCY: Nuclear Regulatory... carrying out its responsibilities for monitoring DOE's waste disposal activities at the F-Area Tank Farm at... the availability of ``U.S. Nuclear Regulatory Commission Plan for Monitoring Disposal Actions Taken by...

Kelch-like ECH-associated Protein 1-dependent Nuclear Factor-E2-related Factor 2 Activation in Relation to Antioxidation Induced by Sevoflurane Preconditioning.

PubMed

Cai, Min; Tong, Li; Dong, Beibei; Hou, Wugang; Shi, Likai; Dong, Hailong

2017-03-01

The authors have reported that antioxidative effects play a crucial role in the volatile anesthetic-induced neuroprotection. Accumulated evidence shows that endogenous antioxidation could be up-regulated by nuclear factor-E2-related factor 2 through multiple pathways. However, whether nuclear factor-E2-related factor 2 activation is modulated by sevoflurane preconditioning and, if so, what is the signaling cascade underlying upstream of this activation are still unknown. Sevoflurane preconditioning in mice was performed with sevoflurane (2.5%) 1 h per day for five consecutive days. Focal cerebral ischemia/reperfusion injury was induced by middle cerebral artery occlusion. Expression of nuclear factor-E2-related factor 2, kelch-like ECH-associated protein 1, manganese superoxide dismutase, thioredoxin-1, and nicotinamide adenine dinucleotide phosphate quinolone oxidoreductase-1 was detected (n = 6). The antioxidant activities and oxidative product expression were also examined. To determine the role of kelch-like ECH-associated protein 1 inhibition-dependent nuclear factor-E2-related factor 2 activation in sevoflurane preconditioning-induced neuroprotection, the kelch-like ECH-associated protein 1-nuclear factor-E2-related factor 2 signal was modulated by nuclear factor-E2-related factor 2 knockout, kelch-like ECH-associated protein 1 overexpression lentivirus, and kelch-like ECH-associated protein 1 deficiency small interfering RNA (n = 8). The infarct volume, neurologic scores, and cellular apoptosis were assessed. Sevoflurane preconditioning elicited neuroprotection and increased nuclear factor-E2-related factor 2 nuclear translocation, which in turn up-regulated endogenous antioxidation and reduced oxidative injury. Sevoflurane preconditioning reduced kelch-like ECH-associated protein 1 expression. Nuclear factor-E2-related factor 2 ablation abolished neuroprotection and reversed sevoflurane preconditioning by mediating the up-regulation of antioxidants. Kelch-like ECH-associated protein 1 overexpression reversed nuclear factor-E2-related factor 2 up-regulation and abolished the neuroprotection induced by sevoflurane preconditioning. Kelch-like ECH-associated protein 1 small interfering RNA administration improved nuclear factor-E2-related factor 2 expression and the outcome of mice subjected to ischemia/reperfusion injury. Kelch-like ECH-associated protein 1 down-regulation-dependent nuclear factor-E2-related factor 2 activation underlies the ability of sevoflurane preconditioning to activate the endogenous antioxidant response, which elicits its neuroprotection.

Structural Basis for Activation of Fatty Acid-binding Protein 4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillilan,R.; Ayers, S.; Noy, N.

2007-01-01

Fatty acid-binding protein 4 (FABP4) delivers ligands from the cytosol to the nuclear receptor PPAR{gamma} in the nucleus, thereby enhancing the transcriptional activity of the receptor. Notably, FABP4 binds multiple ligands with a similar affinity but its nuclear translocation is activated only by specific compounds. To gain insight into the structural features that underlie the ligand-specificity in activation of the nuclear import of FABP4, we solved the crystal structures of the protein complexed with two compounds that induce its nuclear translocation, and compared these to the apo-protein and to FABP4 structures bound to non-activating ligands. Examination of these structures indicatesmore » that activation coincides with closure of a portal loop phenylalanine side-chain, contraction of the binding pocket, a subtle shift in a helical domain containing the nuclear localization signal of the protein, and a resultant change in oligomeric state that exposes the nuclear localization signal to the solution. Comparisons of backbone displacements induced by activating ligands with a measure of mobility derived from translation, libration, screw (TLS) refinement, and with a composite of slowest normal modes of the apo state suggest that the helical motion associated with the activation of the protein is part of the repertoire of the equilibrium motions of the apo-protein, i.e. that ligand binding does not induce the activated configuration but serves to stabilize it. Nuclear import of FABP4 can thus be understood in terms of the pre-existing equilibrium hypothesis of ligand binding.« less

p35 Regulates the CRM1-Dependent Nucleocytoplasmic Shuttling of Nuclear Hormone Receptor Coregulator-Interacting Factor 1 (NIF-1)

PubMed Central

Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W. Y.; Li, Zhen; Fu, Amy K. Y.; Ip, Nancy Y.

2014-01-01

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators. PMID:25329792

p35 regulates the CRM1-dependent nucleocytoplasmic shuttling of nuclear hormone receptor coregulator-interacting factor 1 (NIF-1).

PubMed

Zhao, Xiao-Su; Fu, Wing-Yu; Chien, Winnie W Y; Li, Zhen; Fu, Amy K Y; Ip, Nancy Y

2014-01-01

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase, which plays critical roles in a wide spectrum of neuronal functions including neuronal survival, neurite outgrowth, and synapse development and plasticity. Cdk5 activity is controlled by its specific activators: p35 or p39. While knockout studies reveal that Cdk5/p35 is critical for neuronal migration during early brain development, functions of Cdk5/p35 have been unraveled through the identification of the interacting proteins of p35, most of which are Cdk5/p35 substrates. However, it remains unclear whether p35 can regulate neuronal functions independent of Cdk5 activity. Here, we report that a nuclear protein, nuclear hormone receptor coregulator (NRC)-interacting factor 1 (NIF-1), is a new interacting partner of p35. Interestingly, p35 regulates the functions of NIF-1 independent of Cdk5 activity. NIF-1 was initially discovered as a transcriptional regulator that enhances the transcriptional activity of nuclear hormone receptors. Our results show that p35 interacts with NIF-1 and regulates its nucleocytoplasmic trafficking via the nuclear export pathway. Furthermore, we identified a nuclear export signal on p35; mutation of this site or blockade of the CRM1/exportin-dependent nuclear export pathway resulted in the nuclear accumulation of p35. Intriguingly, blocking the nuclear export of p35 attenuated the nuclear accumulation of NIF-1. These findings reveal a new p35-dependent mechanism in transcriptional regulation that involves the nucleocytoplasmic shuttling of transcription regulators.

tRNAs promote nuclear import of HIV-1 intracellular reverse transcription complexes.

PubMed

Zaitseva, Lyubov; Myers, Richard; Fassati, Ariberto

2006-10-01

Infection of non-dividing cells is a biological property of HIV-1 crucial for virus transmission and AIDS pathogenesis. This property depends on nuclear import of the intracellular reverse transcription and pre-integration complexes (RTCs/PICs). To identify cellular factors involved in nuclear import of HIV-1 RTCs, cytosolic extracts were fractionated by chromatography and import activity examined by the nuclear import assay. A near-homogeneous fraction was obtained, which was active in inducing nuclear import of purified and labeled RTCs. The active fraction contained tRNAs, mostly with defective 3' CCA ends. Such tRNAs promoted HIV-1 RTC nuclear import when synthesized in vitro. Active tRNAs were incorporated into and recovered from virus particles. Mutational analyses indicated that the anticodon loop mediated binding to the viral complex whereas the T-arm may interact with cellular factors involved in nuclear import. These tRNA species efficiently accumulated into the nucleus on their own in a energy- and temperature-dependent way. An HIV-1 mutant containing MLV gag did not incorporate tRNA species capable of inducing HIV-1 RTC nuclear import and failed to infect cell cycle-arrested cells. Here we provide evidence that at least some tRNA species can be imported into the nucleus of human cells and promote HIV-1 nuclear import.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saad, Fawzy A.; Harvard Medical School, Boston, MA 02115; Torres, Marie

LOX, the principal enzyme involved in crosslinking of collagen, was the first of several lysyl oxidase isotypes to be characterized. Its active form was believed to be exclusively extracellular. Active LOX was later reported to be present in cell nuclei; its function there is unknown. LOX expression opposes the effect of mutationally activated Ras, which is present in about 30% of human cancers. The mechanism of LOX in countering the action of Ras is also unknown. In the present work, assessment of nuclear protein for possible effects of lysyl oxidase activity led to the discovery that proliferating cells dramatically increasemore » their nuclear protein content when exposed to BAPN ({beta}-aminopropionitrile), a highly specific lysyl oxidase inhibitor that reportedly blocks LOX inhibition of Ras-induced oocyte maturation. In three cell types (PC12 cells, A7r5 smooth muscle cells, and NIH 3T3 fibroblasts), BAPN caused a 1.8-, 1.7-, and 2.1-fold increase in total nuclear protein per cell, respectively, affecting all major components in both nuclear matrix and chromatin fractions. Since nuclear size is correlated with proliferative status, enzyme activity restricting nuclear growth may be involved in the lysyl oxidase tumor suppressive effect. Evidence is also presented for the presence of apparent lysyl oxidase isotype(s) containing a highly conserved LOX active site sequence in the nuclei of PC12 cells, which do not manufacture extracellular lysyl oxidase substrates. Results reported here support the hypothesis that nuclear lysyl oxidase regulates nuclear growth, and thereby modulates cell proliferation.« less

77 FR 6827 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-09

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0280] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission. ACTION: Notice of pending NRC action to... public comment. SUMMARY: The Nuclear Regulatory Commission (NRC) invites public comment about our...

Neural net controlled tag gas sampling system for nuclear reactors

DOEpatents

Gross, K.C.; Laug, M.T.; Lambert, J.B.; Herzog, J.P.

1997-02-11

A method and system are disclosed for providing a tag gas identifier to a nuclear fuel rod and analyze escaped tag gas to identify a particular failed nuclear fuel rod. The method and system include disposing a unique tag gas composition into a plenum of a nuclear fuel rod, monitoring gamma ray activity, analyzing gamma ray signals to assess whether a nuclear fuel rod has failed and is emitting tag gas, activating a tag gas sampling and analysis system upon sensing tag gas emission from a failed nuclear rod and evaluating the escaped tag gas to identify the particular failed nuclear fuel rod. 12 figs.

Death-domain associated protein-6 (DAXX) mediated apoptosis in hantavirus infection is counter-balanced by activation of interferon-stimulated nuclear transcription factors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khaiboullina, Svetlana F., E-mail: sv.khaiboullina@gmail.com; Morzunov, Sergey P.; Boichuk, Sergei V.

2013-09-01

Hantaviruses are negative strand RNA species that replicate predominantly in the cytoplasm. They also activate numerous cellular responses, but their involvement in nuclear processes is yet to be established. Using human umbilical vein endothelial cells (HUVECs), this study investigates the molecular finger-print of nuclear transcription factors during hantavirus infection. The viral-replication-dependent activation of pro-myelocytic leukemia protein (PML) was followed by subsequent localization in nuclear bodies (NBs). PML was also found in close proximity to activated Sp100 nuclear antigen and interferon-stimulated gene 20 kDa protein (ISG-20), but co-localization with death-domain associated protein-6 (DAXX) was not observed. These data demonstrate that hantavirusmore » triggers PML activation and localization in NBs in the absence of DAXX-PLM-NB co-localization. The results suggest that viral infection interferes with DAXX-mediated apoptosis, and expression of interferon-activated Sp100 and ISG-20 proteins may indicate intracellular intrinsic antiviral attempts.« less

Hope, connectedness, and action: responses of adolescents and young adults to the threat of nuclear war

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fernald, M.C.

This study undertook to assess the degree to which a person's sense of interconnectedness with others may have a mediating effect on whether one reacts to the consciousness of nuclear threat with feelings of despair (helplessness and hopelessness) or with a sense of empowerment (hope, efficacy, and action for change). Subjects included 119 public high school students and 14 Friends' school students, ranging from 12-18 years of age; 58 university students ranging from 18-25 years of age; and 24 parents of public school students, 10 adult Friends, and 38 members of Physicians for Social Responsibility, ranging from 20-83 years ofmore » age. A self-rating questionnaire was administered to assess subjects' conscious level of concern about nuclear issues, feelings of connectedness with others in general and about nuclear concerns, feelings of hope and efficacy in general and with regard to nuclear issues, and participation in activities reflecting concerns about nuclear threat. Correlational analyses (multiple regression, Spearman Rho, Kendall's Tau) showed that general feelings of hope, level of activity, and feelings of connectedness about nuclear concerns were the best predictors of hope about nuclear concerns. Conscious level of concern and feelings of connectedness about nuclear concerns, along with age and SES were the best predictors of an active response to nuclear threat; additionally, parents' level of concern about nuclear issues was predictive of their children's degree of activity in response to nuclear threat. Adolescents' level of concern and degree of connectedness with others was predicted by their parents' degree of connectedness.« less

Do We Need Plant Food Supplements? A Critical Examination of Quality, Safety, Efficacy, and Necessity for a New Regulatory Framework.

PubMed

Abdel-Tawab, Mona

2018-04-01

Given the expanding market of plant food supplements (PFSs) not undergoing any pre-marketing authorization, the overall quality, safety and efficacy of PFSs were subjected to a critical examination. Although many high-quality PFSs exist on the legal market, quality concerns are in general justified. Besides economic adulteration, active ingredients dramatically differing from label claims and among products were reported in several studies. In addition, PFSs sold via the Internet may be intentionally adulterated with undeclared prescription drugs. Compared to PFSs with only one single herb, PFSs containing herbal mixtures were more involved in moderate and severe clinical courses. Although prohibited by regulation, misleading labels on PFSs are common. Above all, only vague evidence for the efficacy of PFSs exists. Notwithstanding the unproven efficacy and insufficient safety assessment, PFSs represent a relevant source for consumers to get access to herbal preparations in the United States and meanwhile also in Europe, as launching of licensed/registered European herbal medicinal products (HMPs) has steadily decreased. However, being non-vitamin, non-mineral products, PFSs are neither food nor drugs. In terms of protecting public health and providing the consumer with high-quality, effective, and safe PFSs, possibilities are shown how to deal with the many challenges of PFSs. Last but not least, suggestions are made for assigning PFSs a separate regulatory category being less regulated compared to HMPs but more strictly regulated compared to food laws including implementation of good manufacturing practices and a scientific pre-marketing review process by an expert commission. Georg Thieme Verlag KG Stuttgart · New York.

Nuclear calcium is required for human T cell activation

PubMed Central

Samstag, Yvonne

2016-01-01

Calcium signals in stimulated T cells are generally considered single entities that merely trigger immune responses, whereas costimulatory events specify the type of reaction. Here we show that the “T cell calcium signal” is a composite signal harboring two distinct components that antagonistically control genomic programs underlying the immune response. Using human T cells from healthy individuals, we establish nuclear calcium as a key signal in human T cell adaptogenomics that drives T cell activation and is required for signaling to cyclic adenosine monophosphate response element–binding protein and the induction of CD25, CD69, interleukin-2, and γ-interferon. In the absence of nuclear calcium signaling, cytosolic calcium activating nuclear factor of activated T cells translocation directed the genomic response toward enhanced expression of genes that negatively modulate T cell activation and are associated with a hyporesponsive state. Thus, nuclear calcium controls the T cell fate decision between a proliferative immune response and tolerance. Modulators of nuclear calcium–driven transcription may be used to develop a new type of pro-tolerance immunosuppressive therapy. PMID:27810914

Development and Validation of a Polarimetric-MCScene 3D Atmospheric Radiation Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berk, Alexander; Hawes, Frederick; Fox, Marsha

2016-03-15

Polarimetric measurements can substantially enhance the ability of both spectrally resolved and single band imagery to detect the proliferation of weapons of mass destruction, providing data for locating and identifying facilities, materials, and processes of undeclared and proliferant nuclear weapons programs worldwide. Unfortunately, models do not exist that efficiently and accurately predict spectral polarized signatures for the materials of interest embedded in complex 3D environments. Having such a model would enable one to test hypotheses and optimize both the enhancement of scene contrast and the signal processing for spectral signature extraction. The Phase I set the groundwork for development ofmore » fully validated polarimetric spectral signature and scene simulation models. This has been accomplished 1. by (a) identifying and downloading state-of-the-art surface and atmospheric polarimetric data sources, (b) implementing tools for generating custom polarimetric data, and (c) identifying and requesting US Government funded field measurement data for use in validation; 2. by formulating an approach for upgrading the radiometric spectral signature model MODTRAN to generate polarimetric intensities through (a) ingestion of the polarimetric data, (b) polarimetric vectorization of existing MODTRAN modules, and (c) integration of a newly developed algorithm for computing polarimetric multiple scattering contributions; 3. by generating an initial polarimetric model that demonstrates calculation of polarimetric solar and lunar single scatter intensities arising from the interaction of incoming irradiances with molecules and aerosols; 4. by developing a design and implementation plan to (a) automate polarimetric scene construction and (b) efficiently sample polarimetric scattering and reflection events, for use in a to be developed polarimetric version of the existing first-principles synthetic scene simulation model, MCScene; and 5. by planning a validation field measurement program in collaboration with the Remote Sensing and Exploitation group at Sandia National Laboratories (SNL) in which data from their ongoing polarimetric field and laboratory measurement program will be shared and, to the extent allowed, tailored for model validation in exchange for model predictions under conditions and for geometries outside of their measurement domain.« less

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Nuclear Safety. Technical progress journal, April--June 1996: Volume 37, No. 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muhlheim, M D

1996-01-01

This journal covers significant issues in the field of nuclear safety. Its primary scope is safety in the design, construction, operation, and decommissioning of nuclear power reactors worldwide and the research and analysis activities that promote this goal, but it also encompasses the safety aspects of the entire nuclear fuel cycle, including fuel fabrication, spent-fuel processing and handling, nuclear waste disposal, the handling of fissionable materials and radioisotopes, and the environmental effects of all these activities.

Nuclear Safety. Technical progress journal, January--March 1994: Volume 35, No. 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silver, E G

1994-01-01

This is a journal that covers significant issues in the field of nuclear safety. Its primary scope is safety in the design, construction, operation, and decommissioning of nuclear power reactors worldwide and the research and analysis activities that promote this goal, but it also encompasses the safety aspects of the entire nuclear fuel cycle, including fuel fabrication, spent-fuel processing and handling, and nuclear waste disposal, the handling of fissionable materials and radioisotopes, and the environmental effects of all these activities.

Roles of the nuclear lamina in stable nuclear association and assembly of a herpesviral transactivator complex on viral immediate-early genes.

PubMed

Silva, Lindsey; Oh, Hyung Suk; Chang, Lynne; Yan, Zhipeng; Triezenberg, Steven J; Knipe, David M

2012-01-01

Little is known about the mechanisms of gene targeting within the nucleus and its effect on gene expression, but most studies have concluded that genes located near the nuclear periphery are silenced by heterochromatin. In contrast, we found that early herpes simplex virus (HSV) genome complexes localize near the nuclear lamina and that this localization is associated with reduced heterochromatin on the viral genome and increased viral immediate-early (IE) gene transcription. In this study, we examined the mechanism of this effect and found that input virion transactivator protein, virion protein 16 (VP16), targets sites adjacent to the nuclear lamina and is required for targeting of the HSV genome to the nuclear lamina, exclusion of heterochromatin from viral replication compartments, and reduction of heterochromatin on the viral genome. Because cells infected with the VP16 mutant virus in1814 showed a phenotype similar to that of lamin A/C(-/-) cells infected with wild-type virus, we hypothesized that the nuclear lamina is required for VP16 activator complex formation. In lamin A/C(-/-) mouse embryo fibroblasts, VP16 and Oct-1 showed reduced association with the viral IE gene promoters, the levels of VP16 and HCF-1 stably associated with the nucleus were lower than in wild-type cells, and the association of VP16 with HCF-1 was also greatly reduced. These results show that the nuclear lamina is required for stable nuclear localization and formation of the VP16 activator complex and provide evidence for the nuclear lamina being the site of assembly of the VP16 activator complex. The targeting of chromosomes in the cell nucleus is thought to be important in the regulation of expression of genes on the chromosomes. The major documented effect of intranuclear targeting has been silencing of chromosomes at sites near the nuclear periphery. In this study, we show that targeting of the herpes simplex virus DNA genome to the nuclear periphery promotes formation of transcriptional activator complexes on the viral genome, demonstrating that the nuclear periphery also has sites for activation of transcription. These results highlight the importance of the nuclear lamina, the structure that lines the inner nuclear membrane, in both transcriptional activation and repression. Future studies defining the molecular structures of these two types of nuclear sites should define new levels of gene regulation.

Activin A stimulates IkappaB-alpha/NFkappaB and RANK expression for osteoclast differentiation, but not AKT survival pathway in osteoclast precursors.

PubMed

Sugatani, T; Alvarez, U M; Hruska, K A

2003-09-01

Recent studies have reported that activin A enhances osteoclastogenesis in cultures of mouse bone marrow cells stimulated with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). However, the exact mechanisms by which activin A functions during osteoclastogenesis are not clear. RANKL stimulation of RANK/TRAF6 signaling increases nuclear factor-kappaB (NFkappaB) nuclear translocation and activates the Akt/PKB cell survival pathway. Here we report that activin A alone activates IkappaB-alpha, and stimulates nuclear translocation of NFkappaB and receptor activator of nuclear factor-kappaB (RANK) expression for osteoclastogenesis, but not Akt/PKB survival signal transduction including BAD and mammalian target of rapamycin (mTOR) for survival in osteoclast precursors in vitro. Activin A alone failed to activate Akt, BAD, and mTOR by immunoblotting, and it also failed to prevent apoptosis in osteoclast precursors. While activin A activated IkappaB-alpha and induced nuclear translocation of phosphorylated-NFkappaB, and it also enhanced RANK expression in osteoclast precursors. Moreover, activin A enhanced RANKL- and M-CSF-stimulated nuclear translocation of NFkappaB. Our data suggest that activin A enhances osteoclastogenesis treated with RANKL and M-CSF via stimulation of RANK, thereby increasing the RANKL stimulation. Activin A alone activated the NFkappaB pathway, but not survival in osteoclast precursors in vitro, but it is, thus, insufficient as a sole stimulus to osteoclastogenesis. Copyright 2003 Wiley-Liss, Inc.

The Activities of the European Consortium on Nuclear Data Development and Analysis for Fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fischer, U., E-mail: ulrich.fischer@kit.edu; Avrigeanu, M.; Avrigeanu, V.

This paper presents an overview of the activities of the European Consortium on Nuclear Data Development and Analysis for Fusion. The Consortium combines available European expertise to provide services for the generation, maintenance, and validation of nuclear data evaluations and data files relevant for ITER, IFMIF and DEMO, as well as codes and software tools required for related nuclear calculations.

Audit Report Office of the Inspector General: Defense Nuclear Agency Activities at Johnston Atoll

DTIC Science & Technology

1989-12-15

DEPARTMENT OF DEFENSE AUDIT REPORT DEFENSE NUCLEAR AGENCY ACTIVITIES AT JOHNSTON ATOLL NO. 90-020 December 15, 1989 A&piored tea ggabiic release...a 5330 Accession Number: 5320 Publication Date: Dec 15, 1989 Title: Audit Report Office Of The Inspector General: Defense Nuclear Agency...Descriptors, Keywords: DNA Johnston Atoll Audit Management Economy Efficiency BOS Administration Oversight DOE Nuclear Atmospheric Testing Safeguard

Control of nuclear β-dystroglycan content is crucial for the maintenance of nuclear envelope integrity and function.

PubMed

Vélez-Aguilera, Griselda; de Dios Gómez-López, Juan; Jiménez-Gutiérrez, Guadalupe E; Vásquez-Limeta, Alejandra; Laredo-Cisneros, Marco S; Gómez, Pablo; Winder, Steve J; Cisneros, Bulmaro

2018-02-01

β-Dystroglycan (β-DG) is a plasma membrane protein that has ability to target to the nuclear envelope (NE) to maintain nuclear architecture. Nevertheless, mechanisms controlling β-DG nuclear localization and the physiological consequences of a failure of trafficking are largely unknown. We show that β-DG has a nuclear export pathway in myoblasts that depends on the recognition of a nuclear export signal located in its transmembrane domain, by CRM1. Remarkably, NES mutations forced β-DG nuclear accumulation resulting in mislocalization and decreased levels of emerin and lamin B1 and disruption of various nuclear processes in which emerin (centrosome-nucleus linkage and β-catenin transcriptional activity) and lamin B1 (cell cycle progression and nucleoli structure) are critically involved. In addition to nuclear export, the lifespan of nuclear β-DG is restricted by its nuclear proteasomal degradation. Collectively our data show that control of nuclear β-DG content by the combination of CRM1 nuclear export and nuclear proteasome pathways is physiologically relevant to preserve proper NE structure and activity. Copyright © 2017 Elsevier B.V. All rights reserved.

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10 CFR 810.7 - Generally authorized activities.

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Regulation of NT-PGC-1alpha subcellular localization and function by protein kinase A-dependent modulation of nuclear export by CRM1.

PubMed

Chang, Ji Suk; Huypens, Peter; Zhang, Yubin; Black, Chelsea; Kralli, Anastasia; Gettys, Thomas W

2010-06-04

Peroxisome proliferator-activated receptor gamma co-activator-1alpha (PGC-1alpha) plays a central role in the regulation of cellular energy metabolism and metabolic adaptation to environmental and nutritional stimuli. We recently described a novel, biologically active splice variant of PGC-1alpha (NT-PGC-1alpha, amino acids 1-270) that retains the ability to interact with and transactivate nuclear hormone receptors through its N-terminal transactivation domain. Whereas PGC-1alpha is an unstable nuclear protein sensitive to ubiquitin-mediated targeting to the proteasome, NT-PGC-1alpha is relatively stable and predominantly cytoplasmic, suggesting that its ability to interact with and activate nuclear receptors and transcription factors is dependent upon regulated access to the nucleus. We provide evidence that NT-PGC-1alpha interacts with the nuclear exportin, CRM1, through a specific leucine-rich domain (nuclear export sequence) that regulates its export to the cytoplasm. The nuclear export of NT-PGC-1alpha is inhibited by protein kinase A-dependent phosphorylation of Ser-194, Ser-241, and Thr-256 on NT-PGC-1alpha, which effectively increases its nuclear concentration. Using site-directed mutagenesis to prevent or mimic phosphorylation at these sites, we show that the transcriptional activity of NT-PGC-1alpha is regulated in part through regulation of its subcellular localization. These findings suggest that the function of NT-PGC-1alpha as a transcriptional co-activator is regulated by protein kinase A-dependent inhibition of CRM1-mediated export from the nucleus.

Management of Naturally Occurring Radioactive Materials (NORM) in Canada

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baweja, Anar S.; Tracy, Bliss L.

2008-08-07

In Canada, nuclear and radiological regulatory responsibilities are shared between the provinces/territories and the federal government. The Canadian Nuclear Safety Commission (CNSC) regulates nuclear fuel cycle materials and man-made radionuclides under the Nuclear Safety and Control Act (2000). The provinces and territories regulate NORM arising from industrial activities, not involving the nuclear fuel cycle materials. Present guideline--Canadian Guidelines for the Management of Naturally Occurring Radioactive Materials (NORM)--was published in 2000 in order to bring uniformity to the management of NORM-related procedures to provide adequate radiation protection for workers and the general public. The basic premise of these guidelines is thatmore » the NORM-related activities should not be posing any greater hazard than those activities regulated under the Nuclear Safety and Control Act; these concepts are described in this paper.« less

Protoparvovirus Knocking at the Nuclear Door.

PubMed

Mäntylä, Elina; Kann, Michael; Vihinen-Ranta, Maija

2017-10-02

Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural changes in the nuclear envelope, and is completed by intranuclear disassembly of capsids and chromatinization of the viral genome. This review discusses the nuclear import strategies of protoparvoviruses and describes its dynamics comprising active and passive movement, and directed and diffusive motion of capsids in the molecularly crowded environment of the cell.

Viral mimicry of Cdc2/cyclin-dependent kinase 1 mediates disruption of nuclear lamina during human cytomegalovirus nuclear egress.

PubMed

Hamirally, Sofia; Kamil, Jeremy P; Ndassa-Colday, Yasmine M; Lin, Alison J; Jahng, Wan Jin; Baek, Moon-Chang; Noton, Sarah; Silva, Laurie A; Simpson-Holley, Martha; Knipe, David M; Golan, David E; Marto, Jarrod A; Coen, Donald M

2009-01-01

The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser(22)). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser(22) is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle.

JAB1 regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nishimoto, Arata, E-mail: anishimo@yamaguchi-u.ac.jp; Kugimiya, Naruji; Hosoyama, Toru

2013-08-30

Highlights: •JAB1 interacted with unphosphorylated STAT3 in the nucleus. •JAB1 knockdown tended to increase nuclear STAT3 expression. •JAB1 knockdown significantly decreased unphosphorylated STAT3 DNA-binding activity. •JAB1 knockdown significantly decreased MDR1, NANOG, and VEGF expressions. •Nuclear JAB1, but not nuclear STAT3, correlated with STAT3 DNA-binding activity. -- Abstract: Recent studies have revealed that unphosphorylated STAT3 forms a dimer, translocates to the nucleus, binds to the STAT3 binding site, and activates the transcription of STAT3 target genes, thereby playing an important role in oncogenesis in addition to phosphorylated STAT3. Among signaling steps of unphosphorylated STAT3, nuclear translocation and target DNA-binding are themore » critical steps for its activation. Therefore, elucidating the regulatory mechanism of these signaling steps of unphosphorylated STAT3 is a potential step in the discovery of a novel cancer drug. However, the mechanism of unphosphorylated STAT3 binding to the promoter of target genes remains unclear. In this study, we focused on Jun activation domain-binding protein 1 (JAB1) as a candidate protein that regulates unphosphorylated STAT3 DNA-binding activity. Initially, we observed that both unphosphorylated STAT3 and JAB1 existed in the nucleus of human colon cancer cell line COLO205 at the basal state (no cytokine stimulation). On the other hand, phosphorylated STAT3 did not exist in the nucleus of COLO205 cells at the basal state. Immunoprecipitation using nuclear extract of COLO205 cells revealed that JAB1 interacted with unphosphorylated STAT3. To investigate the effect of JAB1 on unphosphorylated STAT3 activity, RNAi studies were performed. Although JAB1 knockdown tended to increase nuclear STAT3 expression, it significantly decreased unphosphorylated STAT3 DNA-binding activity. Subsequently, JAB1 knockdown significantly decreased the expression levels of MDR1, NANOG, and VEGF, which are STAT3 target genes. Furthermore, the expression level of nuclear JAB1, but not nuclear STAT3, correlated with unphosphorylated STAT3 DNA-binding activity between COLO205 and LoVo cells. Taken together, these results suggest that nuclear JAB1 positively regulates unphosphorylated STAT3 DNA-binding activity through protein–protein interaction in human colon cancer cell line COLO205.« less

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... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2013-0116] OMB Agency Information Collection Activities: Submission for the Office of Management and Budget Review; Comment Request AGENCY: Nuclear... comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) has recently submitted to OMB for review...

Modeling Nuclear Decay: A Point of Integration between Chemistry and Mathematics.

ERIC Educational Resources Information Center

Crippen, Kent J.; Curtright, Robert D.

1998-01-01

Describes four activities that use graphing calculators to model nuclear-decay phenomena. Students ultimately develop a notion about the radioactive waste produced by nuclear fission. These activities are in line with national educational standards and allow for the integration of science and mathematics. Contains 13 references. (Author/WRM)

75 FR 2894 - Withdrawal of Regulatory Guide 1.148

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-19

... Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' FOR FURTHER INFORMATION... for Active Valve Assemblies in Systems Important to Safety in Nuclear Power Plants.'' RG 1.148 was... qualifying active mechanical equipment used in nuclear power plants. The NRC is withdrawing RG 1.148 because...

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Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

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2012-11-20

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2012-12-20

... upgraded licenses or license renewals to operate the controls at a nuclear reactor facility. This... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2012-0184] Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB) Review; Comment Request AGENCY: Nuclear Regulatory...

Differential nuclear remodeling of mammalian somatic cells by Xenopus laevis oocyte and egg cytoplasm

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alberio, Ramiro; Johnson, Andrew D.; Stick, Reimer

2005-07-01

The mechanisms governing nuclear reprogramming have not been fully elucidated yet; however, recent studies show a universally conserved ability of both oocyte and egg components to reprogram gene expression in somatic cells. The activation of genes associated with pluripotency by oocyte/egg components may require the remodeling of nuclear structures, such that they can acquire the features of early embryos and pluripotent cells. Here, we report on the remodeling of the nuclear lamina of mammalian cells by Xenopus oocyte and egg extracts. Lamin A/C is removed from somatic cells incubated in oocyte and egg extracts in an active process that requiresmore » permeable nuclear pores. Removal of lamin A/C is specific, since B-type lamins are not changed, and it is not dependent on the incorporation Xenopus egg specific lamin III. Moreover, transcriptional activity is differentially regulated in somatic cells incubated in the extracts. Pol I and II transcriptions are maintained in cells in oocyte extracts; however, both activities are abolished in egg extracts. Our study shows that components of oocyte and egg extracts can modify the nuclear lamina of somatic cells and that this nuclear remodeling induces a structural change in the nucleus which may have implications for transcriptional activity. These experiments suggest that modifications in the nuclear lamina structure by the removal of somatic proteins and the incorporation of oocyte/egg components may contribute to the reprogramming of somatic cell nuclei and may define a characteristic configuration of pluripotent cells.« less

Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha

2014-07-18

Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated thatmore » TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.« less

COP1 is required for UV-B–induced nuclear accumulation of the UVR8 photoreceptor

PubMed Central

Skvortsova, Mariya Y.; Loubéry, Sylvain

2016-01-01

The UV-B photoreceptor UV RESISTANCE LOCUS 8 (UVR8) promotes UV-B acclimation and tolerance in Arabidopsis thaliana. UVR8 localizes to both cytosol and nucleus, but its main activity is assumed to be nuclear. UV-B photoreception stimulates nuclear accumulation of UVR8 in a presently unknown manner. Here, we show that CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) is required for UV-B–induced nuclear accumulation of UVR8, but bypassing the COP1 requirement for UVR8 nuclear accumulation did not rescue the cop1 mutant UV-B phenotype. Using a glucocorticoid receptor (GR)-based fusion protein system to conditionally localize GR-UVR8 to the nucleus, we have demonstrated that both photoactivation and nuclear localization of UVR8 are required for UV-B–induced photomorphogenic responses. In contrast, there was no UV-B response when UV-B–activated UVR8 was artificially retained in the cytosol. In agreement with a predominantly nuclear activity, constitutively active UVR8W285A accumulated in the nucleus also in the absence of UV-B. Furthermore, GR-COP1 expression lines suggested that UV-B–activated UVR8 can be coimported into the nucleus by COP1. Our data strongly support localization of UVR8 signaling in the nucleus and a dual role for COP1 in the regulation of UV-B–induced UVR8 nuclear accumulation and in UVR8-mediated UV-B signaling. PMID:27407149

Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Compagnucci, Claudia; Barresi, Sabina; Petrini, Stefania

2015-04-03

Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify amore » new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.« less

Nuclear BK Channels Regulate Gene Expression via the Control of Nuclear Calcium Signaling

PubMed Central

Li, Boxing; Jie, Wei; Huang, Lianyan; Wei, Peng; Li, Shuji; Luo, Zhengyi; Friedman, Allyson K.; Meredith, Andrea L.; Han, Ming-Hu; Zhu, Xin-Hong; Gao, Tian-Ming

2014-01-01

Ion channels are essential for the regulation of neuronal functions. The significance of plasma membrane, mitochondrial, endoplasmic reticulum, and lysosomal ion channels in the regulation of Ca2+ is well established. In contrast, surprisingly less is known about the function of ion channels on the nuclear envelope (NE). Here we demonstrate the presence of functional large-conductance, calcium-activated potassium channels (BK channels) on the NE of rodent hippocampal neurons. Functionally blockade of nuclear BK channels (nBK channels) induces NE-derived Ca2+ release, nucleoplasmic Ca2+ elevation, and cAMP response element binding protein (CREB)-dependent transcription. More importantly, blockade of nBK channels regulates nuclear Ca2+-sensitive gene expression and promotes dendritic arborization in a nuclear Ca2+-dependent manner. These results suggest that nBK channel functions as a molecular linker between neuronal activity and nuclear Ca2+ to convey the signals from synapse to nucleus and is a new modulator for synaptic activity-dependent neuronal functions at the NE level. PMID:24952642

The relationship between early ego strength and adolescent responses to the threat of nuclear war

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrekus, N.J.

Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war,more » how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development.« less

AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lorenzato, Annalisa; Biolatti, Marta; Institute for Cancer Research at Candiolo, Candiolo, Torino

The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancermore » cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. - highlights: • CSE1L is a key player in nucleocytoplasmic traffic by forming complex with Ran. • AKT phosphorylates RanBP3 that regulates the nucleocytoplasmic gradient of Ran. • The activated oncogenic AKT drives the nuclear accumulation of CSE1L. • CSE1L in the nucleus up-regulates genes conveying pro-oncogenic signals. • CSE1L might contribute to tumor progression driven by the activated oncogenic AKT.« less

A novel NADP(+)-dependent dehydrogenase activity for 7alpha/beta- and 11beta-hydroxysteroids in human liver nuclei: A third 11beta-hydroxysteroid dehydrogenase.

PubMed

Robinzon, B; Prough, R A

2009-06-15

Human tissue from uninvolved liver of cancer patients was fractionated using differential centrifugation and characterized for 11betaHSD enzyme activity against corticosterone, dehydrocorticosterone, 7alpha- and 7beta-hydroxy-dehydroepiandrosterone, and 7-oxo-dehydroepiandrosterone. An enzyme activity was observed in nuclear protein fractions that utilized either NADP(+) or NAD(+), but not NADPH and NADH, as pyridine nucleotide cofactor with K(m) values of 12+/-2 and 390+/-2microM, compared to the K(m) for microsomal 11betaHSD1 of 43+/-8 and 264+/-24microM, respectively. The K(m) for corticosterone in the NADP(+)-dependent nuclear oxidation reaction was 102+/-16nM, compared to 4.3+/-0.8microM for 11betaHSD1. The K(cat) values for nuclear activity with NADP(+) was 1687nmol/min/mg/micromol, compared to 755nmol/min/mg/micromol for microsomal 11betaHSD1 activity. Inhibitors of 11betaHSD1 decreased both nuclear and microsomal enzyme activities, suggesting that the nuclear activity may be due to an enzyme similar to 11betaHSD Type 1 and 2.

A Novel NADP+- Dependent Dehydrogenase Activity for 7 α/β and 11 β-hydroxysteroids in human liver nuclei: A Third 11 β-Hydroxysteroid Dehydrogenase

PubMed Central

Robinzon, B.; Prough, R.A.

2009-01-01

Human tissue from uninvolved liver of cancer patients was fractionated using differential centrifugation and characterized for 11βHSD enzyme activity against corticosterone, dehydrocorticosterone, 7α and 7β-hydroxy-dehydroepiandrosterone, and 7-oxodehydroepiandrosterone. An enzyme activity was observed in nuclear protein fractions that utilized either NADP+ or NAD+, but not NADPH and NADH, as pyridine nucleotide cofactor with Km values of 12 ± 2 and 390 ± 2 μM, compared to the Km for microsomal 11βHSD1 of 43 ± 8 and 264 ± 24 μM, respectively. The Km for corticosterone in the NADP+-dependent nuclear oxidation reaction was 102 ± 16 nM, compared to 4.3 ± 0.8 μM for 11βHSD1. The Kcat values for nuclear activity with NADP+ was 1,687 nmol/min/mg/μmol, compared to 755 nmol/min/mg/μmol for microsomal 11βHSD1 activity. Inhibitors of 11βHSD1 decreased both nuclear and microsomal enzyme activities, suggesting that the nuclear activity may be due to an enzyme similar to 11βHSD Type 1 and 2. PMID:19416720

MicroRNA-22 and microRNA-140 suppress NF-{kappa}B activity by regulating the expression of NF-{kappa}B coactivators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takata, Akemi; Otsuka, Motoyuki, E-mail: otsukamo-tky@umin.ac.jp; Kojima, Kentaro

2011-08-12

Highlights: {yields} miRNAs were screened for their ability to regulate NF-{kappa}B activity. {yields} miRNA-22 and miRNA-140-3p suppress NF-{kappa}B activity by regulating coactivators. {yields} miRNA-22 targets nuclear receptor coactivator 1 (NCOA1). {yields} miRNA-140-3p targets nuclear receptor-interacting protein 1 (NRIP1). -- Abstract: Nuclear factor {kappa}B (NF-{kappa}B) is a transcription factor that regulates a set of genes that are critical to many biological phenomena, including liver tumorigenesis. To identify microRNAs (miRNAs) that regulate NF-{kappa}B activity in the liver, we screened 60 miRNAs expressed in hepatocytes for their ability to modulate NF-{kappa}B activity. We found that miRNA-22 and miRNA-140-3p significantly suppressed NF-{kappa}B activity bymore » regulating the expression of nuclear receptor coactivator 1 (NCOA1) and nuclear receptor-interacting protein 1 (NRIP1), both of which are NF-{kappa}B coactivators. Our results provide new information about the roles of miRNAs in the regulation of NF-{kappa}B activity.« less

14C content in vegetation in the vicinities of Brazilian nuclear power reactors.

PubMed

Dias, Cíntia Melazo; Santos, Roberto Ventura; Stenström, Kristina; Nícoli, Iêda Gomes; Skog, Göran; da Silveira Corrêa, Rosangela

2008-07-01

(14)C specific activities were measured in grass samples collected around Brazilian nuclear power reactors. The specific activity values varied between 227 and 299 Bq/kg C. Except for two samples which showed (14)C specific activities 22% above background values, half of the samples showed background specific activities, and the other half had a (14)C excess of 1-18%. The highest specific activities were found close to the nuclear power plants and along the main wind directions (NE and NNE). The activity values were found to decrease with increasing distance from the reactors. The unexpectedly high (14)C excess values found in two samples were related to the local topography, which favors (14)C accumulation and limits the dispersion of the plume. The results indicate a clear (14)C anthropogenic signal within 5 km around the nuclear power plants which is most prominent along northeastwards, the prevailing wind direction.

Nuclear event zero-time calculation and uncertainty evaluation.

PubMed

Pan, Pujing; Ungar, R Kurt

2012-04-01

It is important to know the initial time, or zero-time, of a nuclear event such as a nuclear weapon's test, a nuclear power plant accident or a nuclear terrorist attack (e.g. with an improvised nuclear device, IND). Together with relevant meteorological information, the calculated zero-time is used to help locate the origin of a nuclear event. The zero-time of a nuclear event can be derived from measured activity ratios of two nuclides. The calculated zero-time of a nuclear event would not be complete without an appropriately evaluated uncertainty term. In this paper, analytical equations for zero-time and the associated uncertainty calculations are derived using a measured activity ratio of two nuclides. Application of the derived equations is illustrated in a realistic example using data from the last Chinese thermonuclear test in 1980. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores.

PubMed

Elosegui-Artola, Alberto; Andreu, Ion; Beedle, Amy E M; Lezamiz, Ainhoa; Uroz, Marina; Kosmalska, Anita J; Oria, Roger; Kechagia, Jenny Z; Rico-Lastres, Palma; Le Roux, Anabel-Lise; Shanahan, Catherine M; Trepat, Xavier; Navajas, Daniel; Garcia-Manyes, Sergi; Roca-Cusachs, Pere

2017-11-30

YAP is a mechanosensitive transcriptional activator with a critical role in cancer, regeneration, and organ size control. Here, we show that force applied to the nucleus directly drives YAP nuclear translocation by decreasing the mechanical restriction of nuclear pores to molecular transport. Exposure to a stiff environment leads cells to establish a mechanical connection between the nucleus and the cytoskeleton, allowing forces exerted through focal adhesions to reach the nucleus. Force transmission then leads to nuclear flattening, which stretches nuclear pores, reduces their mechanical resistance to molecular transport, and increases YAP nuclear import. The restriction to transport is further regulated by the mechanical stability of the transported protein, which determines both active nuclear transport of YAP and passive transport of small proteins. Our results unveil a mechanosensing mechanism mediated directly by nuclear pores, demonstrated for YAP but with potential general applicability in transcriptional regulation. Copyright © 2017 Elsevier Inc. All rights reserved.

Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation.

PubMed

Nayebosadri, Arman; Ji, Julie Y

2013-08-01

The lamina serves to maintain the nuclear structure and stiffness while acting as a scaffold for heterochromatin and many transcriptional proteins. Its role in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In this study, we successfully silenced lamin A/C in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to dexamethasone and shear stress. Nuclear translocation of GR, an anti-inflammatory nuclear receptor, in response to dexamethasone or shear stress (5, 10, and 25 dyn/cm(2)) was observed via time-lapse cell imaging and quantified using a Bayesian image analysis algorithm. Transcriptional activity of the GRE promoter was assessed using a dual-luciferase reporter plasmid. We found no dependence on nuclear lamina for GR translocation from the cytoplasm into the nucleus. However, the absence of lamin A/C led to significantly increased expression of luciferase under dexamethasone and shear stress induction as well as changes in histone protein function. PCR results for NF-κB inhibitor alpha (NF-κBIA) and dual specificity phosphatase 1 (DUSP1) genes further supported our luciferase data with increased expression in the absence of lamin. Our results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus, but nuclear lamina is important to properly regulate GRE transcription. Nuclear lamina, rather than histone deacetylase (HDAC), is a more significant mediator of shear stress-induced transcriptional activity, while dexamethasone-initiated transcription is more HDAC dependent. Our findings provide more insights into the molecular pathways involved in nuclear mechanotransduction.

Endothelial nuclear lamina is not required for glucocorticoid receptor nuclear import but does affect receptor-mediated transcription activation

PubMed Central

Nayebosadri, Arman

2013-01-01

The lamina serves to maintain the nuclear structure and stiffness while acting as a scaffold for heterochromatin and many transcriptional proteins. Its role in endothelial mechanotransduction, specifically how nuclear mechanics impact gene regulation under shear stress, is not fully understood. In this study, we successfully silenced lamin A/C in bovine aortic endothelial cells to determine its role in both glucocorticoid receptor (GR) nuclear translocation and glucocorticoid response element (GRE) transcriptional activation in response to dexamethasone and shear stress. Nuclear translocation of GR, an anti-inflammatory nuclear receptor, in response to dexamethasone or shear stress (5, 10, and 25 dyn/cm2) was observed via time-lapse cell imaging and quantified using a Bayesian image analysis algorithm. Transcriptional activity of the GRE promoter was assessed using a dual-luciferase reporter plasmid. We found no dependence on nuclear lamina for GR translocation from the cytoplasm into the nucleus. However, the absence of lamin A/C led to significantly increased expression of luciferase under dexamethasone and shear stress induction as well as changes in histone protein function. PCR results for NF-κB inhibitor alpha (NF-κBIA) and dual specificity phosphatase 1 (DUSP1) genes further supported our luciferase data with increased expression in the absence of lamin. Our results suggest that absence of lamin A/C does not hinder passage of GR into the nucleus, but nuclear lamina is important to properly regulate GRE transcription. Nuclear lamina, rather than histone deacetylase (HDAC), is a more significant mediator of shear stress-induced transcriptional activity, while dexamethasone-initiated transcription is more HDAC dependent. Our findings provide more insights into the molecular pathways involved in nuclear mechanotransduction. PMID:23703529

OECD/NEA Ongoing activities related to the nuclear fuel cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cornet, S.M.; McCarthy, K.; Chauvin, N.

2013-07-01

As part of its role in encouraging international collaboration, the OECD Nuclear Energy Agency is coordinating a series of projects related to the Nuclear Fuel Cycle. The Nuclear Science Committee (NSC) Working Party on Scientific Issues of the Nuclear Fuel Cycle (WPFC) comprises five different expert groups covering all aspects of the fuel cycle from front to back-end. Activities related to fuels, materials, physics, separation chemistry, and fuel cycles scenarios are being undertaken. By publishing state-of-the-art reports and organizing workshops, the groups are able to disseminate recent research advancements to the international community. Current activities mainly focus on advanced nuclearmore » systems, and experts are working on analyzing results and establishing challenges associated to the adoption of new materials and fuels. By comparing different codes, the Expert Group on Advanced Fuel Cycle Scenarios is aiming at gaining further understanding of the scientific issues and specific national needs associated with the implementation of advanced fuel cycles. At the back end of the fuel cycle, separation technologies (aqueous and pyrochemical processing) are being assessed. Current and future activities comprise studies on minor actinides separation and post Fukushima studies. Regular workshops are also organized to discuss recent developments on Partitioning and Transmutation. In addition, the Nuclear Development Committee (NDC) focuses on the analysis of the economics of nuclear power across the fuel cycle in the context of changes of electricity markets, social acceptance and technological advances and assesses the availability of the nuclear fuel and infrastructure required for the deployment of existing and future nuclear power. The Expert Group on the Economics of the Back End of the Nuclear Fuel Cycle (EBENFC), in particular, is looking at assessing economic and financial issues related to the long term management of spent nuclear fuel. (authors)« less

Protein kinase A is part of a mechanism that regulates nuclear reimport of the nuclear tRNA export receptors Los1p and Msn5p.

PubMed

Pierce, Jacqueline B; van der Merwe, George; Mangroo, Dev

2014-02-01

The two main signal transduction mechanisms that allow eukaryotes to sense and respond to changes in glucose availability in the environment are the cyclic AMP (cAMP)/protein kinase A (PKA) and AMP-activated protein kinase (AMPK)/Snf1 kinase-dependent pathways. Previous studies have shown that the nuclear tRNA export process is inhibited in Saccharomyces cerevisiae deprived of glucose. However, the signal transduction pathway involved and the mechanism by which glucose availability regulates nuclear-cytoplasmic tRNA trafficking are not understood. Here, we show that inhibition of nuclear tRNA export is caused by a block in nuclear reimport of the tRNA export receptors during glucose deprivation. Cytoplasmic accumulation of the tRNA export receptors during glucose deprivation is not caused by activation of Snf1p. Evidence obtained suggests that PKA is part of the mechanism that regulates nuclear reimport of the tRNA export receptors in response to glucose availability. This mechanism does not appear to involve phosphorylation of the nuclear tRNA export receptors by PKA. The block in nuclear reimport of the tRNA export receptors appears to be caused by activation of an unidentified mechanism when PKA is turned off during glucose deprivation. Taken together, the data suggest that PKA facilitates return of the tRNA export receptors to the nucleus by inhibiting an unidentified activity that facilitates cytoplasmic accumulation of the tRNA export receptors when glucose in the environment is limiting. A PKA-independent mechanism was also found to regulate nuclear tRNA export in response to glucose availability. This mechanism, however, does not regulate nuclear reimport of the tRNA export receptors.

Protein Kinase A Is Part of a Mechanism That Regulates Nuclear Reimport of the Nuclear tRNA Export Receptors Los1p and Msn5p

PubMed Central

Pierce, Jacqueline B.; van der Merwe, George

2014-01-01

The two main signal transduction mechanisms that allow eukaryotes to sense and respond to changes in glucose availability in the environment are the cyclic AMP (cAMP)/protein kinase A (PKA) and AMP-activated protein kinase (AMPK)/Snf1 kinase-dependent pathways. Previous studies have shown that the nuclear tRNA export process is inhibited in Saccharomyces cerevisiae deprived of glucose. However, the signal transduction pathway involved and the mechanism by which glucose availability regulates nuclear-cytoplasmic tRNA trafficking are not understood. Here, we show that inhibition of nuclear tRNA export is caused by a block in nuclear reimport of the tRNA export receptors during glucose deprivation. Cytoplasmic accumulation of the tRNA export receptors during glucose deprivation is not caused by activation of Snf1p. Evidence obtained suggests that PKA is part of the mechanism that regulates nuclear reimport of the tRNA export receptors in response to glucose availability. This mechanism does not appear to involve phosphorylation of the nuclear tRNA export receptors by PKA. The block in nuclear reimport of the tRNA export receptors appears to be caused by activation of an unidentified mechanism when PKA is turned off during glucose deprivation. Taken together, the data suggest that PKA facilitates return of the tRNA export receptors to the nucleus by inhibiting an unidentified activity that facilitates cytoplasmic accumulation of the tRNA export receptors when glucose in the environment is limiting. A PKA-independent mechanism was also found to regulate nuclear tRNA export in response to glucose availability. This mechanism, however, does not regulate nuclear reimport of the tRNA export receptors. PMID:24297441

Standardization of administered activities in pediatric nuclear medicine: a report of the first nuclear medicine global initiative project, part 1-statement of the issue and a review of available resources.

PubMed

Fahey, Frederic H; Bom, Henry Hee-Seong; Chiti, Arturo; Choi, Yun Young; Huang, Gang; Lassmann, Michael; Laurin, Norman; Mut, Fernando; Nuñez-Miller, Rodolfo; O'Keeffe, Darin; Pradhan, Prasanta; Scott, Andrew M; Song, Shaoli; Soni, Nischal; Uchiyama, Mayuki; Vargas, Luis

2015-04-01

The Nuclear Medicine Global Initiative (NMGI) was formed in 2012 and consists of 13 international organizations with direct involvement in nuclear medicine. The underlying objectives of the NMGI were to promote human health by advancing the field of nuclear medicine and molecular imaging, encourage global collaboration in education, and harmonize procedure guidelines and other policies that ultimately lead to improvements in quality and safety in the field throughout the world. For its first project, the NMGI decided to consider the issues involved in the standardization of administered activities in pediatric nuclear medicine. This article presents part 1 of the final report of this initial project of the NMGI. It provides a review of the value of pediatric nuclear medicine, the current understanding of the carcinogenic risk of radiation as it pertains to the administration of radiopharmaceuticals in children, and the application of dosimetric models in children. A listing of pertinent educational and reference resources available in print and online is also provided. The forthcoming part 2 report will discuss current standards for administered activities in children and adolescents that have been developed by various organizations and an evaluation of the current practice of pediatric nuclear medicine specifically with regard to administered activities as determined by an international survey of nuclear medicine clinics and centers. Lastly, the part 2 report will recommend a path forward toward global standardization of the administration of radiopharmaceuticals in children. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

The Role of Ect2 Nuclear RhoGEF Activity in Ovarian Cancer Cell Transformation

PubMed Central

Huff, Lauren P.; DeCristo, Molly J.; Trembath, Dimitri; Kuan, Pei Fen; Yim, Margaret; Liu, Jinsong; Cook, Danielle R.; Miller, C. Ryan; Der, Channing J.

2013-01-01

Ect2, a Rho guanine nucleotide exchange factor (RhoGEF), is atypical among RhoGEFs in its predominantly nuclear localization in interphase cells. One current model suggests that Ect2 mislocalization drives cellular transformation by promoting aberrant activation of cytoplasmic Rho family GTPase substrates. However, in ovarian cancers, where Ect2 is both amplified and overexpressed at the mRNA level, we observed that the protein is highly expressed and predominantly nuclear and that nuclear but not cytoplasmic Ect2 increases with advanced disease. Knockdown of Ect2 in ovarian cancer cell lines impaired their anchorage-independent growth without affecting their growth on plastic. Restoration of Ect2 expression rescued the anchorage-independent growth defect, but not if either the DH catalytic domain or the nuclear localization sequences of Ect2 were mutated. These results suggested a novel mechanism whereby Ect2 could drive transformation in ovarian cancer cells by acting as a RhoGEF specifically within the nucleus. Interestingly, Ect2 had an intrinsically distinct GTPase specificity profile in the nucleus versus the cytoplasm. Nuclear Ect2 bound preferentially to Rac1, while cytoplasmic Ect2 bound to RhoA but not Rac. Consistent with nuclear activation of endogenous Rac, Ect2 overexpression was sufficient to recruit Rac effectors to the nucleus, a process that required a functional Ect2 catalytic domain. Furthermore, expression of active nuclearly targeted Rac1 rescued the defect in transformed growth caused by Ect2 knockdown. Our work suggests a novel mechanism of Ect2-driven transformation, identifies subcellular localization as a regulator of GEF specificity, and implicates activation of nuclear Rac1 in cellular transformation. PMID:24386507

10 CFR 52.91 - Authorization to conduct limited work authorization activities.

Code of Federal Regulations, 2012 CFR

2012-01-01

... determination required by 10 CFR 50.10(e), and the Director of New Reactors or the Director of Nuclear Reactor... activities. 52.91 Section 52.91 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.91 Authorization to conduct limited work...

10 CFR 52.91 - Authorization to conduct limited work authorization activities.

Code of Federal Regulations, 2013 CFR

2013-01-01

... determination required by 10 CFR 50.10(e), and the Director of New Reactors or the Director of Nuclear Reactor... activities. 52.91 Section 52.91 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.91 Authorization to conduct limited work...

10 CFR 52.91 - Authorization to conduct limited work authorization activities.

Code of Federal Regulations, 2014 CFR

2014-01-01

... determination required by 10 CFR 50.10(e), and the Director of New Reactors or the Director of Nuclear Reactor... activities. 52.91 Section 52.91 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.91 Authorization to conduct limited work...

10 CFR 52.91 - Authorization to conduct limited work authorization activities.

Code of Federal Regulations, 2011 CFR

2011-01-01

... determination required by 10 CFR 50.10(e), and the Director of New Reactors or the Director of Nuclear Reactor... activities. 52.91 Section 52.91 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.91 Authorization to conduct limited work...

10 CFR 52.91 - Authorization to conduct limited work authorization activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... determination required by 10 CFR 50.10(e), and the Director of New Reactors or the Director of Nuclear Reactor... activities. 52.91 Section 52.91 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSES, CERTIFICATIONS, AND APPROVALS FOR NUCLEAR POWER PLANTS Combined Licenses § 52.91 Authorization to conduct limited work...

Quantitative Analysis Reveals that Actin and Src-Family Kinases Regulate Nuclear YAP1 and Its Export.

PubMed

Ege, Nil; Dowbaj, Anna M; Jiang, Ming; Howell, Michael; Hooper, Steven; Foster, Charles; Jenkins, Robert P; Sahai, Erik

2018-06-08

The transcriptional regulator YAP1 is critical for the pathological activation of fibroblasts. In normal fibroblasts, YAP1 is located in the cytoplasm, while in activated cancer-associated fibroblasts, it is nuclear and promotes the expression of genes required for pro-tumorigenic functions. Here, we investigate the dynamics of YAP1 shuttling in normal and activated fibroblasts, using EYFP-YAP1, quantitative photobleaching methods, and mathematical modeling. Imaging of migrating fibroblasts reveals the tight temporal coupling of cell shape change and altered YAP1 localization. Both 14-3-3 and TEAD binding modulate YAP1 shuttling, but neither affects nuclear import. Instead, we find that YAP1 nuclear accumulation in activated fibroblasts results from Src and actomyosin-dependent suppression of phosphorylated YAP1 export. Finally, we show that nuclear-constrained YAP1, upon XPO1 depletion, remains sensitive to blockade of actomyosin function. Together, these data place nuclear export at the center of YAP1 regulation and indicate that the cytoskeleton can regulate YAP1 within the nucleus. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Development of Curricula for Nuclear Radiation Protection, Nuclear Instrumentation, and Nuclear Materials Processing Technologies. Final Report.

ERIC Educational Resources Information Center

Hull, Daniel M.

A study was conducted to assist two-year postsecondary educational institutions in providing technical specialty courses for preparing nuclear technicians. As a result of project activities, curricula have been developed for five categories of nuclear technicians and operators: (1) radiation protection technician, (2) nuclear instrumentation and…

The Alarmin Properties of DNA and DNA-associated Nuclear Proteins.

PubMed

Magna, Melinda; Pisetsky, David S

2016-05-01

The communication of cell injury and death is a critical element in host defense. Although immune cells can serve this function by elaborating cytokines and chemokines, somatic cells can repurpose nuclear macromolecules to function as damage-associated molecular patterns (DAMPs) or alarmins to exert similar activity. Among these molecules, DNA, high-mobility group box-1, and histone proteins can all act as DAMPs once they are in an extracellular location. This review describes current information on the role of the nuclear DAMPs, their translocation to the outside of cells, and pathways of activation after uptake into the inside of immune cells. MEDLINE and PubMed databases were searched for citations (1990-2016) in English related to the following terms: DAMPs, high-mobility group box-1, DNA, histones, cell death, danger, and immune activation. Selected articles with the most relevant studies were included for a more detailed consideration. Although nuclear molecules have important structural and genetic regulatory roles inside the cell nucleus, when released into the extracellular space during cell death, these molecules can acquire immune activity and serve as alarmins or DAMPs. Although apoptosis is generally considered the source of extracellular nuclear material, other cell death pathways such as necroptosis, NETosis, and pyroptosis can contribute to the release of nuclear molecules. Importantly, the release of nuclear DAMPs occurs with both soluble and particulate forms of these molecules. The activity of nuclear molecules may depend on posttranslational modifications, redox changes, and the binding of other molecules. Once in an extracellular location, nuclear DAMPs can engage the same pattern recognition receptors as do pathogen-associated molecular patterns. These interactions can activate immune cells and lead to cytokine and chemokine production. Among these receptors, internal receptors for DNA are key to the response to this molecule; the likely function of these internal sensors is the recognition of DNA from intracellular infection by bacteria or viruses. Activation of these receptors requires translocation of extracellular DNA into specialized compartments. In addition to nuclear DNA, mitochondrial DNA can also serve as a DAMP. The communication of cell injury and death is a critical element in host defense and involves the repurposing of nuclear molecules as immune triggers. As such, the presence of extracellular nuclear material can serve as novel biomarkers for conditions involving cell injury and death. Targeting of these molecules may also represent an important new approach to therapy. Published by Elsevier Inc.

Identification of Modulators of the Nuclear Receptor Peroxisome Proliferator-Activated Receptor α (PPARα) in a Mouse Liver Gene Expression Compendium

EPA Science Inventory

The nuclear receptor family member peroxisome proliferator-activated receptor α (PPARα) is activated by therapeutic hypolipidemic drugs and environmentally-relevant chemicals to regulate genes involved in lipid transport and catabolism. Chronic activation of PPARα in rodents inc...

The nuclear lamina as a gene-silencing hub.

PubMed

Shevelyov, Yuri Y; Nurminsky, Dmitry I

2012-01-01

There is accumulating evidence that the nuclear periphery is a transcriptionally repressive compartment. A surprisingly large fraction of the genome is either in transient or permanent contact with nuclear envelope, where the majority of genes are maintained in a silent state, waiting to be awakened during cell differentiation. The integrity of the nuclear lamina and the histone deacetylase activity appear to be essential for gene repression at the nuclear periphery. However, the molecular mechanisms of silencing, as well as the events that lead to the activation of lamina-tethered genes, require further elucidation. This review summarizes recent advances in understanding of the mechanisms that link nuclear architecture, local chromatin structure, and gene regulation.

Development and validation of a rapid test system for detection of pork meat and collagen residues.

PubMed

Masiri, J; Benoit, L; Barrios-Lopez, B; Thienes, C; Meshgi, M; Agapov, A; Dobritsa, A; Nadala, C; Samadpour, M

2016-11-01

Mislabeling, contamination, and economic adulteration of meat products with undeclared pork tissues are illegal under regulations promulgated by numerous regulatory agencies. Nonetheless, analysis of the European meat industry has revealed pervasive meat adulteration, necessitating more extensive application of meat authentication testing. As existing methods for meat speciation require specialized equipment and/or training, we developed a detection system based on a lateral flow device (LFD) assay format capable of rapidly (~35min) identifying porcine residues derived from raw meat, cooked meat, and gelatin down to 0.01%, 1.0%, and 2.5% contamination, respectively. Specificity analysis revealed no cross-reactivity with meat derived from chicken, turkey, horse, beef, lamb, or goat. Comparison with a commercial ELISA kit and PCR method revealed similar if not improved sensitivity, with the added feature that the LFD-based system required considerably less time to perform. Accordingly, this test system should aid the food industry and food control authorities in monitoring for adulteration with pork. Copyright © 2016 Elsevier Ltd. All rights reserved.

Detection of DNA from undeclared animal species in commercial elimination diets for dogs using PCR.

PubMed

Horvath-Ungerboeck, Christa; Widmann, Karoline; Handl, Stefanie

2017-08-01

Elimination diets are the gold standard for the diagnosis of adverse food reactions (AFR). A broad variety of commercial diets are available containing either hydrolysed protein or novel ingredients which claim to be suitable for elimination diets. Contamination may be one factor accounting for the failure of commercial elimination diet trials. To test commercial diets labelled as suitable for elimination diets for dogs, for DNA of animal origin other than that declared on the label. Twelve commercial dry and tinned dog food products were investigated for DNA of animal origin (chicken, turkey, beef, mutton and pork) using PCR testing. In nine of 10 over-the-counter diets, DNA of one or more animal species other than declared on the label was identified. The DNA most frequently detected was derived from beef (n = 8) and pork (n = 6). Two hydrolysed diets only contained DNA of the declared animal source. Over-the-counter "single protein diets" or canned meat products cannot be recommended for the diagnosis of dogs with AFR because contamination may cause the elimination diet to fail. © 2017 ESVD and ACVD.

Cross-linking of surface Ig receptors on murine B lymphocytes stimulates the expression of nuclear tetradecanoyl phorbol acetate-response element-binding proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiles, T.C.; Liu, J.L.; Rothstein, T.L.

1991-03-15

Cross-linking of sIg on primary B lymphocytes leads to increased nuclear DNA-binding activity specific for the tetradecanoyl phorbol acetate-response element (TRE), as judged by gel mobility shift assays. Stimulation of B cells to enter S phase of the cell cycle by treatment with the combination of phorbol ester plus calcium ionophore also stimulated nuclear TRE-binding activity within 2 h, with maximal expression at 4 h; however, phorbol ester and calcium ionophore were not as effective in stimulating binding activity when examined separately. Stimulated nuclear expression of TRE-binding activity appears to require protein synthesis. Fos- and Jun/AP-1-related proteins participate directly inmore » the identified nucleoprotein complex, as shown by the ability of c-fos- and c-jun-specific antisera to either alter or completely abolish electrophoretic migration of the complex in native gels. Further, UV photo-cross-linking studies identified two major TRE-binding protein species, whose sizes correspond to TRE-binding proteins derived from HeLa cell nuclear extracts. The results suggest that in primary B cells nuclear TRE-binding activity represents a downstream signaling event that occurs subsequent to changes in protein kinase C activity and intracellular Ca2+ but that can be triggered physiologically through sIg.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Yi, E-mail: yihooyi@gmail.com; Ericsson, Ida, E-mail: ida.ericsson@ntnu.no; Doseth, Berit, E-mail: berit.doseth@ntnu.no

Activation-induced cytidine deaminase (AID) is the mutator enzyme in adaptive immunity. AID initiates the antibody diversification processes in activated B cells by deaminating cytosine to uracil in immunoglobulin genes. To some extent other genes are also targeted, which may lead to genome instability and B cell malignancy. Thus, it is crucial to understand its targeting and regulation mechanisms. AID is regulated at several levels including subcellular compartmentalization. However, the complex nuclear distribution and trafficking of AID has not been studied in detail previously. In this work, we examined the subnuclear localization of AID and its interaction partner CTNNBL1 and foundmore » that they associate with spliceosome-associated structures including Cajal bodies and nuclear speckles. Moreover, protein kinase A (PKA), which activates AID by phosphorylation at Ser38, is present together with AID in nuclear speckles. Importantly, we demonstrate that AID physically associates with the major spliceosome subunits (small nuclear ribonucleoproteins, snRNPs), as well as other essential splicing components, in addition to the transcription machinery. Based on our findings and the literature, we suggest a transcription-coupled splicing-associated model for AID targeting and activation. - Highlights: • AID and its interaction partner CTNNBL1 localize to Cajal bodies and nuclear speckles. • AID associates with its activating kinase PKA in nuclear speckles. • AID is linked to the splicing machinery in switching B-cells. • Our findings suggest a transcription-coupled splicing associated mechanism for AID targeting and activation.« less

AKT activation drives the nuclear localization of CSE1L and a pro-oncogenic transcriptional activation in ovarian cancer cells.

PubMed

Lorenzato, Annalisa; Biolatti, Marta; Delogu, Giuseppe; Capobianco, Giampiero; Farace, Cristiano; Dessole, Salvatore; Cossu, Antonio; Tanda, Francesco; Madeddu, Roberto; Olivero, Martina; Di Renzo, Maria Flavia

2013-10-15

The human homolog of the yeast cse1 gene (CSE1L) is over-expressed in ovarian cancer. CSE1L forms complex with Ran and importin-α and has roles in nucleocytoplasmic traffic and gene expression. CSE1L accumulated in the nucleus of ovarian cancer cell lines, while it was localized also in the cytoplasm of other cancer cell lines. Nuclear localization depended on AKT, which was constitutively active in ovarian cancer cells, as the CSE1L protein translocated to the cytoplasm when AKT was inactivated. Moreover, the expression of a constitutively active AKT forced the translocation of CSE1L from the cytoplasm to the nucleus in other cancer cells. Nuclear accrual of CSE1L was associated to the nuclear accumulation of the phosphorylated Ran Binding protein 3 (RanBP3), which depended on AKT as well. Also in samples of human ovarian cancer, AKT activation was associated to nuclear accumulation of CSE1L and phosphorylation of RanBP3. Expression profiling of ovarian cancer cells after CSE1L silencing showed that CSE1L was required for the expression of genes promoting invasion and metastasis. In agreement, CSE1L silencing impaired motility and invasiveness of ovarian cancer cells. Altogether these data show that in ovarian cancer cells activated AKT by affecting RanBP3 phosphorylation determines the nuclear accumulation of CSE1L and likely the nuclear concentration of transcription factors conveying pro-oncogenic signals. © 2013 Elsevier Inc. All rights reserved.

Identification of Novel Saccharomyces cerevisiae Proteins with Nuclear Export Activity: Cell Cycle-Regulated Transcription Factor Ace2p Shows Cell Cycle-Independent Nucleocytoplasmic Shuttling

PubMed Central

Jensen, Torben Heick; Neville, Megan; Rain, Jean Christophe; McCarthy, Terri; Legrain, Pierre; Rosbash, Michael

2000-01-01

Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5′ RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G1-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G1 but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner. PMID:11027275

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gastelum, Zoe N.; Harvey, Julia B.

The International Atomic Energy Agency State Evaluation Process: The Role of Information Analysis in Reaching Safeguards Conclusions (Mathews et al. 2008), several examples of nonproliferation models using analytical software were developed that may assist the IAEA with collecting, visualizing, analyzing, and reporting information in support of the State Evaluation Process. This paper focuses on one of the examples a set of models developed in the Proactive Scenario Production, Evidence Collection, and Testing (ProSPECT) software that evaluates the status and nature of a state’s nuclear activities. The models use three distinct subject areas to perform this assessment: the presence of nuclearmore » activities, the consistency of those nuclear activities with national nuclear energy goals, and the geopolitical context in which those nuclear activities are taking place. As a proof-of-concept for the models, a crude case study was performed. The study, which attempted to evaluate the nuclear activities taking place in Syria prior to September 2007, yielded illustrative, yet inconclusive, results. Due to the inconclusive nature of the case study results, changes that may improve the model’s efficiency and accuracy are proposed.« less

Natural compounds regulate energy metabolism by the modulating the activity of lipid-sensing nuclear receptors.

PubMed

Goto, Tsuyoshi; Kim, Young-Il; Takahashi, Nobuyuki; Kawada, Teruo

2013-01-01

Obesity causes excess fat accumulation in various tissues, most notoriously in the adipose tissue, along with other insulin-responsive organs such as skeletal muscle and the liver, which predisposes an individual to the development of metabolic abnormalities. The molecular mechanisms underlying obesity-induced metabolic abnormalities have not been completely elucidated; however, in recent years, the search for therapies to prevent the development of obesity and obesity-associated metabolic disorders has increased. It is known that several nuclear receptors, when activated by specific ligands, regulate carbohydrate and lipid metabolism at the transcriptional level. The expression of lipid metabolism-related enzymes is directly regulated by the activity of various nuclear receptors via their interaction with specific response elements in promoters of those genes. Many natural compounds act as ligands of nuclear receptors and regulate carbohydrate and lipid metabolism by regulating the activities of these nuclear receptors. In this review, we describe our current knowledge of obesity, the role of lipid-sensing nuclear receptors in energy metabolism, and several examples of food factors that act as agonists or antagonists of nuclear receptors, which may be useful for the management of obesity and the accompanying energy metabolism abnormalities. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

PubMed

Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

2017-02-01

HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place. Copyright © 2017 American Society for Microbiology.

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export

PubMed Central

Behrens, Ryan T.; Aligeti, Mounavya; Pocock, Ginger M.; Higgins, Christina A.

2016-01-01

ABSTRACT HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. IMPORTANCE HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place. PMID:27852860

The Orphan Nuclear Receptor TR4 Is a Vitamin A-activated Nuclear Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, X. Edward; Suino-Powell, Kelly M.; Xu, Yong

2015-11-30

Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibitsmore » constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.« less

The nuclear import of ribosomal proteins is regulated by mTOR

PubMed Central

Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

2014-01-01

Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

Materials and Methods for Streamlined Laboratory Analysis of Environmental Samples, FY 2016 Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Addleman, Raymond S.; Naes, Benjamin E.; McNamara, Bruce K.

The International Atomic Energy Agency (IAEA) relies upon laboratory analysis of environmental samples (typically referred to as “swipes”) collected during on-site inspections of safeguarded facilities to support the detection and deterrence of undeclared activities. Unfortunately, chemical processing and assay of the samples is slow and expensive. A rapid, effective, and simple extraction process and analysis method is needed to provide certified results with improved timeliness at reduced costs (principally in the form of reduced labor), while maintaining or improving sensitivity and efficacy. To address these safeguard needs the Pacific Northwest National Laboratory (PNNL) explored and demonstrated improved methods for environmentalmore » sample (ES) analysis. Improvements for both bulk and particle analysis were explored. To facilitate continuity and adoption, the new sampling materials and processing methods will be compatible with existing IAEA protocols for ES analysis. PNNL collaborated with Oak Ridge National Laboratory (ORNL), which performed independent validation of the new bulk analysis methods and compared performance to traditional IAEA’s Network of Analytical Laboratories (NWAL) protocol. ORNL efforts are reported separately. This report describes PNNL’s FY 2016 progress, which was focused on analytical application supporting environmental monitoring of uranium enrichment plants and nuclear fuel processing. In the future the technology could be applied to other safeguard applications and analytes related to fuel manufacturing, reprocessing, etc. PNNL’s FY 2016 efforts were broken into two tasks and a summary of progress, accomplishments and highlights are provided below. Principal progress and accomplishments on Task 1, Optimize Materials and Methods for ICP-MS Environmental Sample Analysis, are listed below. • Completed initial procedure for rapid uranium extraction from ES swipes based upon carbonate-peroxide chemistry (delivered to ORNL for evaluation). • Explored improvements to carbonate-peroxide rapid uranium extraction chemistry. • Evaluated new sampling materials and methods (in collaboration with ORNL). • Demonstrated successful ES extractions from standard and novel swipes for a wide range uranium compounds of interest including UO 2F 2 and UO 2(NO 3) 2, U 3O 8 and uranium ore concentrate. • Completed initial discussions with commercial suppliers of PTFE swipe materials. • Submitted one manuscript for publication. Two additional drafts are being prepared. Principal progress and accomplishments on Task 2, Optimize Materials and Methods for Direct SIMS Environmental Sample Analysis, are listed below. • Designed a SIMS swipe sample holder that retrofits into existing equipment and provides simple, effective, and rapid mounting of ES samples for direct assay while enabling automation and laboratory integration. • Identified preferred conductive sampling materials with better performance characteristics. • Ran samples on the new PNNL NWAL equivalent Cameca 1280 SIMS system. • Obtained excellent agreement between isotopic ratios for certified materials and direct SIMS assay of very low levels of LEU and HEU UO 2F 2 particles on carbon fiber sampling material. Sample activities range from 1 to 500 CPM (uranium mass on sample is dependent upon specific isotope ratio but is frequently in the subnanogram range). • Found that the presence of the UF molecular ions, as measured by SIMS, provides chemical information about the particle that is separate from the uranium isotopics and strongly suggests that those particles originated from an UF6 enrichment activity. • Submitted one manuscript for publication. Another manuscript is in preparation.« less

Nuclear fear and children: the impact of parental nuclear activism, responsivity, and fear

DOE Office of Scientific and Technical Information (OSTI.GOV)

LaGuardia, M.R.

1986-01-01

This study examines the extent to which parental nuclear fear, parental activism, and parental responsivity is associated with children's (age 10) nuclear fear. Other associated variables investigated include: nuclear denial, general anxiety and fear, and the personal characteristics of sex, socio-economic status, and academic aptitude. Findings indicate that children attend to nuclear issues when their parents attend to a significant degree. Children's hopelessness about the arms race is increased as parents' worry about nuclear war increases. Children's fear about not surviving a nuclear war increases as parents' worry about survivability decreases. Children who have more general fears also indicated thatmore » they have a high level of hopelessness, pervasive worry, and much concern about being able to survive a nuclear war. Children with a high degree of general anxiety did not indicate high degrees of nuclear fears. Children with high academic aptitude were more knowledgeable about nuclear issues and expressed more fears about the nuclear threat. Boys demonstrated more knowledge about nuclear issues than girls, and girls expressed much more frequent fear and worry about the nuclear threat than boys. Parents of lower socio-economic statues (SES) expressed more denial about the nuclear threat and were more pro-military than the higher SES parents.« less

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs

PubMed Central

Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L

2017-01-01

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation. PMID:28990926

IRAK2 directs stimulus-dependent nuclear export of inflammatory mRNAs.

PubMed

Zhou, Hao; Bulek, Katarzyna; Li, Xiao; Herjan, Tomasz; Yu, Minjia; Qian, Wen; Wang, Han; Zhou, Gao; Chen, Xing; Yang, Hui; Hong, Lingzi; Zhao, Junjie; Qin, Luke; Fukuda, Koichi; Flotho, Annette; Gao, Ji; Dongre, Ashok; Carman, Julie A; Kang, Zizhen; Su, Bing; Kern, Timothy S; Smith, Jonathan D; Hamilton, Thomas A; Melchior, Frauke; Fox, Paul L; Li, Xiaoxia

2017-10-09

Expression of inflammatory genes is determined in part by post-transcriptional regulation of mRNA metabolism but how stimulus- and transcript-dependent nuclear export influence is poorly understood. Here, we report a novel pathway in which LPS/TLR4 engagement promotes nuclear localization of IRAK2 to facilitate nuclear export of a specific subset of inflammation-related mRNAs for translation in murine macrophages. IRAK2 kinase activity is required for LPS-induced RanBP2-mediated IRAK2 sumoylation and subsequent nuclear translocation. Array analysis showed that an SRSF1-binding motif is enriched in mRNAs dependent on IRAK2 for nuclear export. Nuclear IRAK2 phosphorylates SRSF1 to reduce its binding to target mRNAs, which promotes the RNA binding of the nuclear export adaptor ALYREF and nuclear export receptor Nxf1 loading for the export of the mRNAs. In summary, LPS activates a nuclear function of IRAK2 that facilitates the assembly of nuclear export machinery to export selected inflammatory mRNAs to the cytoplasm for translation.

The peroxisome proliferator-activated receptor: A family of nuclear receptors role in various diseases

PubMed Central

Tyagi, Sandeep; Gupta, Paras; Saini, Arminder Singh; Kaushal, Chaitnya; Sharma, Saurabh

2011-01-01

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors of nuclear hormone receptor superfamily comprising of the following three subtypes: PPARα, PPARγ, and PPARβ/δ. Activation of PPAR-α reduces triglyceride level and is involved in regulation of energy homeostasis. Activation of PPAR-γ causes insulin sensitization and enhances glucose metabolism, whereas activation of PPAR-β/δ enhances fatty acids metabolism. Thus, PPAR family of nuclear receptors plays a major regulatory role in energy homeostasis and metabolic function. The present review critically analyzes the protective and detrimental effect of PPAR agonists in dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. PMID:22247890

1996 NRC annual report. Volume 13

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1997-10-01

This 22nd annual report of the US Nuclear Regulatory Commission (NRC) describes accomplishments, activities, and plans made during Fiscal Year 1996 (FH 1996)--October 1, 1995, through September 30, 1996. Significant activities that occurred early in FY 1997 are also described, particularly changes in the Commission and organization of the NRC. The mission of the NRC is to ensure that civilian uses of nuclear materials in the US are carried out with adequate protection of public health and safety, the environment, and national security. These uses include the operation of nuclear power plants and fuel cycle plants and medical, industrial, andmore » research applications. Additionally, the NRC contributes to combating the proliferation of nuclear weapons material worldwide. The NRC licenses and regulates commercial nuclear reactor operations and research reactors and other activities involving the possession and use of nuclear materials and wastes. It also protects nuclear materials used in operation and facilities from theft or sabotage. To accomplish its statutorily mandated regulatory mission, the NRC issues rules and standards, inspects facilities and operations, and issues any required enforcement actions.« less

Annual Report to Congress of the Atomic Energy Commission for 1965

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seaborg, Glenn T.

1966-01-31

The document represents the 1965 Annual Report of the Atomic Energy Commission (AEC) to Congress. The report opens with a Foreword - a letter from President Lyndon B. Johnson. The main portion is divided into 3 major sections for 1965, plus 10 appendices and the index. Section names and chapters are as follows. Part One reports on Developmental and Promotional Activities with the following chapters: (1) The Atomic Energy Program - 1965; (2) The Industrial Base ; (3) Industrial Relations; (4) Operational Safety; (5) Source and Special Nuclear Materials Production; (6) The Nuclear Defense Effort; (7) Civilian Nuclear Power; (8)more » Nuclear Space Applications; (9) Auxiliary Electrical Power for Land and Sea; (10) Military Reactors; (11) Advanced Reactor Technology and Nuclear Safety Research; (12) The Plowshare Program; (13) Isotopes and Radiation Development; (14) Facilities and Projects for Basic Research; (15) International Cooperation; and, (16) Nuclear Education and Information. Part Two reports on Regulatory Activities with the following chapters: (1) Licensing and Regulating the Atom; (2) Reactors and other Nuclear Facilities; and, (3) Control of Radioactive Materials. Part Three reports on Adjudicatory Activities.« less

The Hsp90 Inhibitor, 17-AAG, Prevents the Ligand-Independent Nuclear Localization of Androgen Receptor in Refractory Prostate Cancer Cells

PubMed Central

Saporita, Anthony J.; Ai, Junkui; Wang, Zhou

2010-01-01

BACKGROUND Androgen receptor (AR) is the key molecule in androgen-refractory prostate cancer. Despite androgen ablative conditions, AR remains active and is necessary for the growth of androgen-refractory prostate cancer cells. Nuclear localization of AR is a prerequisite for its transcriptional activation. We examined AR localization in androgen-dependent and androgen-refractory prostate cancer cells. METHODS AND RESULTS We demonstrate increased nuclear localization of a GFP-tagged AR in the absence of hormone in androgen-refractory C4-2 cells compared to parental androgen-sensitive human prostate cancer LNCaP cells. Analysis of AR mutants impaired in ligand-binding indicates that the nuclear localization of AR in C4-2 cells is truly androgen-independent. The hsp90 inhibitor, 17-allylamino-17-demethoxygeldanamycin (17-AAG), inhibits basal PSA expression and disrupts the ligand-independent nuclear localization of AR at doses much lower than required to inhibit androgen-induced nuclear import. CONCLUSIONS Hsp90 is a key regulator of ligand-independent nuclear localization and activation of AR in androgen-refractory prostate cancer cells. PMID:17221841

Nuclear location of a chromatin insulator in Drosophila melanogaster.

PubMed

Xu, Qinghao; Li, Mo; Adams, Jessica; Cai, Haini N

2004-03-01

Chromatin-related functions are associated with spatial organization in the nucleus. We have investigated the relationship between the enhancer-blocking activity and subnuclear localization of the Drosophila melanogaster suHw insulator. Using fluorescent in situ hybridization, we observed that genomic loci containing the gypsy retrotransposon were distributed closer to the nuclear periphery than regions without the gypsy retrotransposon. However, transgenes containing a functional 340 bp suHw insulator did not exhibit such biased distribution towards the nuclear periphery, which suggests that the suHw insulator sequence is not responsible for the peripheral localization of the gypsy retrotransposon. Antibody stains showed that the two proteins essential for the suHw insulator activity, SUHW and MOD(MDG4), are not restricted to the nuclear periphery. The enhancer-blocking activity of suHw remained intact under the heat shock conditions, which was shown to disrupt the association of gypsy, SUHW and MOD(MDG4) with the nuclear periphery. Our results indicate that the suHw insulator can function in the nuclear interior, possibly through local interactions with chromatin components or other nuclear structures.

A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

PubMed Central

Mahajan, Muktar A.; Samuels, Herbert H.

2000-01-01

We describe the cloning and characterization of a new family of nuclear receptor coregulators (NRCs) which modulate the function of nuclear hormone receptors in a ligand-dependent manner. NRCs are expressed as alternatively spliced isoforms which may exhibit different intrinsic activities and receptor specificities. The NRCs are organized into several modular structures and contain a single functional LXXLL motif which associates with members of the steroid hormone and thyroid hormone/retinoid receptor subfamilies with high affinity. Human NRC (hNRC) harbors a potent N-terminal activation domain (AD1), which is as active as the herpesvirus VP16 activation domain, and a second activation domain (AD2) which overlaps with the receptor-interacting LXXLL region. The C-terminal region of hNRC appears to function as an inhibitory domain which influences the overall transcriptional activity of the protein. Our results suggest that NRC binds to liganded receptors as a dimer and this association leads to a structural change in NRC resulting in activation. hNRC binds CREB-binding protein (CBP) with high affinity in vivo, suggesting that hNRC may be an important functional component of a CBP complex involved in mediating the transcriptional effects of nuclear hormone receptors. PMID:10866662

Nuclear arms threat: psychosocial correlates of attitudes and behavioral response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chilstrom, G.A.

1985-01-01

Why do some Americans believe a mutual (US-USSR) freeze on nuclear weapons production is the best way to prevent nuclear war, while others believe the strengthening of America's nuclear arsenal is the best answer. This study examined four psychological variables - dogmatism, intolerance of ambiguity, rigidity, and conformity - that might differentiate individuals with these opposing views. Also examined was the question of why some citizens are more actively engaged in peace activity than others. Subjects for the first part of the study were 146 student volunteers, predominantly undergraduate, from San Diego State University. Thirty-eight students were in favor ofmore » additional nuclear arms, while 108 advocated the freeze. The 108 subjects in the freeze group were also used in the second part of the study involving peace activity. In addition, a sample of 47 volunteers from various peace organizations in San Diego County were used to form a peace group. As predicted, individuals favoring a nuclear arms build-up were found to be significantly more rigid and conforming than individuals favoring a mutual freeze. However, no differences in dogmatism or intolerance of ambiguity were found between the two groups. With regard to peace activity, the results indicated that measures of locus of control were not significantly related to anti-nuclear activity, even when political ideology was taken into account. The highly activist peace group was found, however, to be significantly less conforming than the relatively non-activist freeze group.« less

SIRT1 interacts with and protects glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from nuclear translocation: Implications for cell survival after irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joo, Hyun-Yoo; Laboratory of Biochemistry, School of Life Sciences and Biotechnology, Korea University, Seoul 136-713; Woo, Seon Rang

2012-08-10

Highlights: Black-Right-Pointing-Pointer SIRT1 serves to retain GAPDH in the cytosol, preventing GAPDH nuclear translocation. Black-Right-Pointing-Pointer When SIRT1 is depleted, GAPDH translocation occurs even in the absence of stress. Black-Right-Pointing-Pointer Upon irradiation, SIRT1 interacts with GAPDH. Black-Right-Pointing-Pointer SIRT1 prevents irradiation-induced nuclear translocation of GAPDH. Black-Right-Pointing-Pointer SIRT1 presence rather than activity is essential for inhibiting GAPDH translocation. -- Abstract: Upon apoptotic stimulation, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cytosolic enzyme normally active in glycolysis, translocates into the nucleus and activates an apoptotic cascade therein. In the present work, we show that SIRT1 prevents nuclear translocation of GAPDH via interaction with GAPDH. SIRT1 depletion triggeredmore » nuclear translocation of cytosolic GAPDH even in the absence of apoptotic stress. Such translocation was not, however, observed when SIRT1 enzymatic activity was inhibited, indicating that SIRT1 protein per se, rather than the deacetylase activity of the protein, is required to inhibit GAPDH translocation. Upon irradiation, SIRT1 prevented irradiation-induced nuclear translocation of GAPDH, accompanied by interaction of SIRT1 and GAPDH. Thus, SIRT1 functions to retain GAPDH in the cytosol, protecting the enzyme from nuclear translocation via interaction with these two proteins. This serves as a mechanism whereby SIRT1 regulates cell survival upon induction of apoptotic stress by means that include irradiation.« less

The NASA/DOE/DOD nuclear rocket propulsion project - FY 1991 status

NASA Technical Reports Server (NTRS)

Clark, John S.; Miller, Thomas J.

1991-01-01

NASA has initiated planning and critical technology development for nuclear rocket propulsion systems for Space Exploration Initiative missions to the moon and to Mars. Interagency agreements are being negotiated between NASA, the Department of Energy, and the Department of Defense for joint technology development activities. This paper summarizes the activities of the NASA project planning team in FY 1990 that led to the draft Nuclear Propulsion Project Plan, outlines the FY 1991 Interagency activities, and describes the current status of the project plan.

An Unconventional Diacylglycerol Kinase That Regulates Phospholipid Synthesis and Nuclear Membrane Growth*♦

PubMed Central

Han, Gil-Soo; O'Hara, Laura; Carman, George M.; Siniossoglou, Symeon

2008-01-01

Changes in nuclear size and shape during the cell cycle or during development require coordinated nuclear membrane remodeling, but the underlying molecular events are largely unknown. We have shown previously that the activity of the conserved phosphatidate phosphatase Pah1p/Smp2p regulates nuclear structure in yeast by controlling phospholipid synthesis and membrane biogenesis at the nuclear envelope. Two screens for novel regulators of phosphatidate led to the identification of DGK1. We show that Dgk1p is a unique diacylglycerol kinase that uses CTP, instead of ATP, to generate phosphatidate. DGK1 counteracts the activity of PAH1 at the nuclear envelope by controlling phosphatidate levels. Overexpression of DGK1 causes the appearance of phosphatidate-enriched membranes around the nucleus and leads to its expansion, without proliferating the cortical endoplasmic reticulum membrane. Mutations that decrease phosphatidate levels decrease nuclear membrane growth in pah1Δ cells. We propose that phosphatidate metabolism is a critical factor determining nuclear structure by regulating nuclear membrane biogenesis. PMID:18458075

Dual personality of Mad1: regulation of nuclear import by a spindle assembly checkpoint protein.

PubMed

Cairo, Lucas V; Ptak, Christopher; Wozniak, Richard W

2013-01-01

Nuclear transport is a dynamic process that can be modulated in response to changes in cellular physiology. We recently reported that the transport activity of yeast nuclear pore complexes (NPCs) is altered in response to kinetochore-microtubule (KT-MT) interaction defects. Specifically, KT detachment from MTs activates a signaling pathway that prevents the nuclear import of cargos by the nuclear transport factor Kap121p. This loss of Kap121p-mediated import is thought to influence the nuclear environment, including the phosphorylation state of nuclear proteins. A key regulator of this process is the spindle assembly checkpoint protein Mad1p. In response to unattached KTs, Mad1p dynamically cycles between NPCs and KTs. This cycling appears to induce NPC molecular rearrangements that prevent the nuclear import of Kap121p-cargo complexes. Here, we discuss the underlying mechanisms and the physiological relevance of Mad1p cycling and the inhibition of Kap121p-mediated nuclear import, focusing on outstanding questions within the pathway.

Generation of a transgenic medaka (Oryzias latipes) strain for visualization of nuclear dynamics in early developmental stages.

PubMed

Inoue, Takanobu; Iida, Atsuo; Maegawa, Shingo; Sehara-Fujisawa, Atsuko; Kinoshita, Masato

2016-12-01

In this study, we verified nuclear transport activity of an artificial nuclear localization signal (aNLS) in medaka fish (Oryzias latipes). We generated a transgenic medaka strain expresses the aNLS tagged enhanced green fluorescent protein (EGFP) driven by a medaka beta-actin promoter. The aNLS-EGFP was accumulated in the nuclei of somatic tissues and yolk nuclei of oocytes, but undetectable in the spermatozoa. The fluorescent signal was observed from immediately after fertilization by a maternal contribution. Furthermore, male and female pronuclei were visualized in fertilized eggs, and nuclear dynamics of pronuclear fusion and subsequent cleavage were captured by time-lapse imaging. In contrast, SV40NLS exhibited no activity of nuclear transport in early embryos. In conclusion, the aNLS possesses a strong nuclear localization activity and is a useful probe for fluorescent observation of the pronuclei and nuclei in early developmental stage of medaka. © 2016 Japanese Society of Developmental Biologists.

76 FR 3678 - Board Meeting: February 16, 2011-Las Vegas, NV, the U.S. Nuclear Waste Technical Review Board...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-20

... NUCLEAR WASTE TECHNICAL REVIEW BOARD Board Meeting: February 16, 2011--Las Vegas, NV, the U.S. Nuclear Waste Technical Review Board Will Meet To Discuss DOE Activities Related to Managing Spent Nuclear...-203, Nuclear Waste Policy Amendments Act of 1987, the U.S. Nuclear Waste Technical Review Board will...

Active Interrogation for Spent Fuel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swinhoe, Martyn Thomas; Dougan, Arden

2015-11-05

The DDA instrument for nuclear safeguards is a fast, non-destructive assay, active neutron interrogation technique using an external 14 MeV DT neutron generator for characterization and verification of spent nuclear fuel assemblies.

76 FR 30204 - Exelon Nuclear, Dresden Nuclear Power Station, Unit 1; Exemption From Certain Security Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... Power Station, Unit 1; Exemption From Certain Security Requirements 1.0 Background Exelon Nuclear is the licensee and holder of Facility Operating License No. DPR-2 issued for Dresden Nuclear Power Station (DNPS... protection of licensed activities in nuclear power reactors against radiological sabotage,'' paragraph (b)(1...

Nuclear science and society: social inclusion through scientific education

NASA Astrophysics Data System (ADS)

Levy, Denise S.

2017-11-01

This article presents a web-based educational project focused on the potential value of Information and Communication Technology to enhance communication and education on nuclear science throughout Brazil. The project is designed to provide trustworthy information about the beneficial uses of nuclear technology, educating children and teenagers, as well as their parents and teachers, demystifying paradigms and combating misinformation. Making use of a range of interactive activities, the website presents short courses and curiosities, with different themes that comprise the several aspects of the beneficial applications of nuclear science. The intention of the many interactive activities is to encourage research and to enhance learning opportunities through a self-learning universe where the target public is introduced to the basic concepts of nuclear physics, such as nuclides and isotopes, atomic interactions, radioactive decay, biological effects of radiation, nuclear fusion, nuclear fission, nuclear reactors, nuclear medicine, radioactive dating methods and natural occurring radiation, among other ideas and concepts in nuclear physics. Democratization of scientific education can inspire new thoughts, stimulate development and encourage scientific and technological researches.

Exopolyphosphatases in nuclear and mitochondrial fractions during embryogenesis of the hard tick Rhipicephalus (Boophilus) microplus.

PubMed

Campos, Eldo; Façanha, Arnoldo R; Costa, Evenilton P; da Silva Vaz, Itabajara; Masuda, Aoi; Logullo, Carlos

2008-11-01

The present work evaluated polyphosphate (poly P) metabolism in nuclear and mitochondrial fractions during Rhipicephalus microplus embryogenesis. Nuclear poly P decreased and activity of exopolyphosphatase (PPX - polyphosphate-phosphohydrolases; EC 3.6.1.11) increased after embryo cellularization until the end of embryogenesis. The utilization of mitochondrial poly P content occurred between embryo cellularization and segmentation stages. Increasing amounts of total RNA extracted from eggs progressively enhanced nuclear PPX activity, whereas it exerted no effect on mitochondrial PPX activity. The decline in total poly P content after the 7th day of embryogenesis does not reflect the free P(i) increase and the total poly P chain length decrease after embryo cellularization. The Km(app) utilizing poly P(3), poly P(15) and poly P(65) as substrate was almost the same for the nuclear fraction (around 1muM), while the affinity for substrate in mitochondrial fraction was around 10 times higher for poly P(3) (Km(app) = 0.2muM) than for poly P(15) (Km(app) = 2.8muM) and poly P(65) (Km(app) = 3.6muM). PPX activity was stimulated by a factor of two by Mg2+ and Co2+ in the nuclear fraction and only by Mg2+ in the mitochondrial fraction. Heparin (20microg/mL) inhibited nuclear and mitochondrial PPX activity in about 90 and 95% respectively. Together, these data are consistent with the existence of two different PPX isoforms operating in the nuclei and mitochondria of the hard tick R. microplus with distinct metal dependence, inhibitor and activator sensitivities. The data also shed new light on poly P biochemistry during arthropod embryogenesis, opening new routes for future comparative studies on the physiological roles of different poly P pools distributed over cell compartments.

Development of departmental standard for traceability of measured activity for I-131 therapy capsules used in nuclear medicine.

PubMed

Ravichandran, Ramamoorthy; Binukumar, Jp

2011-01-01

International Basic Safety Standards (International Atomic Energy Agency, IAEA) provide guidance levels for diagnostic procedures in nuclear medicine indicating the maximum usual activity for various diagnostic tests in terms of activities of injected radioactive formulations. An accuracy of ± 10% in the activities of administered radio-pharmaceuticals is being recommended, for expected outcome in diagnostic and therapeutic nuclear medicine procedures. It is recommended that the long-term stability of isotope calibrators used in nuclear medicine is to be checked periodically for their performance using a long-lived check source, such as Cs-137, of suitable activity. In view of the un-availability of such a radioactive source, we tried to develop methods to maintain traceability of these instruments, for certifying measured activities for human use. Two re-entrant chambers [(HDR 1000 and Selectron Source Dosimetry System (SSDS)] with I-125 and Ir-192 calibration factors in the Department of Radiotherapy were used to measure Iodine-131 (I-131) therapy capsules to establish traceability to Mark V isotope calibrator of the Department of Nuclear Medicine. Special nylon jigs were fabricated to keep I-131 capsule holder in position. Measured activities in all the chambers showed good agreement. The accuracy of SSDS chamber in measuring Ir-192 activities in the last 5 years was within 0.5%, validating its role as departmental standard for measuring activity. The above method is adopted because mean energies of I-131 and Ir-192 are comparable.

Control of cytoplasmic and nuclear protein kinase A by phosphodiesterases and phosphatases in cardiac myocytes

PubMed Central

Haj Slimane, Zeineb; Bedioune, Ibrahim; Lechêne, Patrick; Varin, Audrey; Lefebvre, Florence; Mateo, Philippe; Domergue-Dupont, Valérie; Dewenter, Matthias; Richter, Wito; Conti, Marco; El-Armouche, Ali; Zhang, Jin; Fischmeister, Rodolphe; Vandecasteele, Grégoire

2014-01-01

Aims The cAMP-dependent protein kinase (PKA) mediates β-adrenoceptor (β-AR) regulation of cardiac contraction and gene expression. Whereas PKA activity is well characterized in various subcellular compartments of adult cardiomyocytes, its regulation in the nucleus remains largely unknown. The aim of the present study was to compare the modalities of PKA regulation in the cytoplasm and nucleus of cardiomyocytes. Methods and results Cytoplasmic and nuclear cAMP and PKA activity were measured with targeted fluorescence resonance energy transfer probes in adult rat ventricular myocytes. β-AR stimulation with isoprenaline (Iso) led to fast cAMP elevation in both compartments, whereas PKA activity was fast in the cytoplasm but markedly slower in the nucleus. Iso was also more potent and efficient in activating cytoplasmic than nuclear PKA. Similar slow kinetics of nuclear PKA activation was observed upon adenylyl cyclase activation with L-858051 or phosphodiesterase (PDE) inhibition with 3-isobutyl-1-methylxantine. Consistently, pulse stimulation with Iso (15 s) maximally induced PKA and myosin-binding protein C phosphorylation in the cytoplasm, but marginally activated PKA and cAMP response element-binding protein phosphorylation in the nucleus. Inhibition of PDE4 or ablation of the Pde4d gene in mice prolonged cytoplasmic PKA activation and enhanced nuclear PKA responses. In the cytoplasm, phosphatase 1 (PP1) and 2A (PP2A) contributed to the termination of PKA responses, whereas only PP1 played a role in the nucleus. Conclusion Our study reveals a differential integration of cytoplasmic and nuclear PKA responses to β-AR stimulation in cardiac myocytes. This may have important implications in the physiological and pathological hypertrophic response to β-AR stimulation. PMID:24550350

An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.

PubMed

Ibarra, Cristián; Vicencio, Jose Miguel; Varas-Godoy, Manuel; Jaimovich, Enrique; Rothermel, Beverly A; Uhlén, Per; Hill, Joseph A; Lavandero, Sergio

2014-10-01

In cardiomyocytes, Ca(2+) plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca(2+) within subcellular microdomains: transcription is regulated by Ca(2+) release within nuclear microdomains, and excitation-contraction coupling is regulated by cytosolic Ca(2+). Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca(2+) signals. However, signaling pathways coupling surface receptor activation to nuclear Ca(2+) release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca(2+) signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca(2+) release from perinuclear Ca(2+) stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca(2+) release. In this review, we discuss mechanisms for the selective control of nuclear Ca(2+) signals with special focus on emerging models of agonist receptor activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Chandra and ALMA observations of the nuclear activity in two strongly lensed star-forming galaxies

NASA Astrophysics Data System (ADS)

Massardi, M.; Enia, A. F. M.; Negrello, M.; Mancuso, C.; Lapi, A.; Vignali, C.; Gilli, R.; Burkutean, S.; Danese, L.; Zotti, G. De

2018-02-01

Aim. According to coevolutionary scenarios, nuclear activity and star formation play relevant roles in the early stages of galaxy formation. We aim at identifying them in high-redshift galaxies by exploiting high-resolution and high-sensitivity X-ray and millimeter-wavelength data to confirm the presence or absence of star formation and nuclear activity and describe their relative roles in shaping the spectral energy distributions and in contributing to the energy budgets of the galaxies. Methods: We present the data, model, and analysis in the X-ray and millimeter (mm) bands for two strongly lensed galaxies, SDP.9 (HATLAS J090740.0-004200) and SDP.11 (HATLAS J091043.1-000322), which we selected in the Herschel-ATLAS catalogs for their excess emission in the mid-IR regime at redshift ≳1.5. This emission suggests nuclear activity in the early stages of galaxy formation. We observed both of them with Chandra ACIS-S in the X-ray regime and analyzed the high-resolution mm data that are available in the ALMA Science Archive for SDP.9. By combining the information available in mm, optical, and X-ray bands, we reconstructed the source morphology. Results: Both targets were detected in the X-ray, which strongly indicates highly obscured nuclear activity. ALMA observations for SDP.9 for the continuum and CO(6-5) spectral line with high resolution (0.02 arcsec corresponding to 65 pc at the distance of the galaxy) allowed us to estimate the lensed galaxy redshift to a better accuracy than pre-ALMA estimates (1.5753 ± 0.0003) and to model the emission of the optical, millimetric, and X-ray band for this galaxy. We demonstrate that the X-ray emission is generated in the nuclear environment, which strongly supports that this object has nuclear activity. On the basis of the X-ray data, we attempt an estimate of the black hole properties in these galaxies. Conclusions: By taking advantage of the lensing magnification, we identify weak nuclear activity associated with high-z galaxies with high star formation rates. This is useful to extend the investigation of the relationship between star formation and nuclear activity to two intrinsically less luminous high-z star-forming galaxies than was possible so far. Given our results for only two objects, they alone cannot constrain the evolutionary models, but provide us with interesting hints and set an observational path toward addressing the role of star formation and nuclear activity in forming galaxies. The reduced images and data cubes as FITS files are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/610/A53

76 FR 65634 - Assistance to Foreign Atomic Energy Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-24

... Nuclear Nonproliferation (NA-20), Office of Nonproliferation and International Security (NA-24), 1000... Administrator for Defense Nuclear Nonproliferation, National Nuclear Security Administration, U.S. Department of...

NNDC Stand: Activities and Services of the National Nuclear Data Center

NASA Astrophysics Data System (ADS)

Pritychenko, B.; Arcilla, R.; Burrows, T. W.; Dunford, C. L.; Herman, M. W.; McLane, V.; Obložinský, P.; Sonzogni, A. A.; Tuli, J. K.; Winchell, D. F.

2005-05-01

The National Nuclear Data Center (NNDC) collects, evaluates, and disseminates nuclear physics data for basic nuclear research, applied nuclear technologies including energy, shielding, medical and homeland security. In 2004, to answer the needs of nuclear data users community, NNDC completed a project to modernize data storage and management of its databases and began offering new nuclear data Web services. The principles of database and Web application development as well as related nuclear reaction and structure database services are briefly described.

Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization

PubMed Central

Näf, Dieter; Kupfer, Gary M.; Suliman, Ahmed; Lambert, Kathleen; D’Andrea, Alan D.

1998-01-01

Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents. Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex. In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA. Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function. Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC. In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability. PMID:9742112

Japans Defense Program Guidelines

DTIC Science & Technology

2013-03-01

matters worse, the tsunami damaged the nuclear reactors at the Tokyo Electric Power Company’s Fukushima 10 Daiichi Nuclear Power Station, causing...response to the nuclear disaster with maximum personnel numbers exceeding 100,000. In order to strengthen those activities, the SDF established the...that prohibits some kinds of military activity.1 After the outbreak of the Korean War, Prime Minister Shigeru Yoshida’s government created a heavily

Compilation of nuclear standards, 9th edition, 1972. Part I. United States activities. Final issue

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

Activities in nuclear standards preparation are presented in tables. Technical, industrial, and environmental organizations preparing standards are listed alphabetically and their activities are given. Approved standards, unapproved drafts, and tentative standards are listed. Standards are indexed by organization and permuted title. (FS)

Nuclear Concepts & Technological Issues Institute: Teacher Activity Booklet.

ERIC Educational Resources Information Center

Davison, Candace C., Ed.; Lunetta, Lois W., Ed.

For many summers the Radiation Science and Engineering Center at Pennsylvania State University has been the site of a Nuclear Concepts and Technological Issues Institute for secondary school science teachers. As a culminating activity of the institute teachers develop lesson plans, laboratory experiments, demonstrations, or other activities and…

78 FR 53173 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2013-0112] Agency Information Collection Activities... for employment), contractors, and consultants of NRC licensees and contractors whose activities involve access to, or control over, special nuclear material at either fixed sites or for transportation...

Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor

PubMed Central

Görner, Wolfram; Durchschlag, Erich; Wolf, Julia; Brown, Elizabeth L.; Ammerer, Gustav; Ruis, Helmut; Schüller, Christoph

2002-01-01

In yeast, environmental conditions control the transcription factor Msn2, the nuclear accumulation and function of which serve as a sensitive indicator of nutrient availablity and environmental stress load. We show here that the nuclear localization signal (NLS) of Msn2 is a direct target of cAMP-dependent protein kinase (cAPK). Genetic analysis suggests that Msn2-NLS function is inhibited by phosphorylation and activated by dephosphorylation. Msn2-NLS function is unaffected by many stress conditions that normally induce nuclear accumulation of full-length Msn2. The Msn2-NLS phosphorylation status is, however, highly sensitive to carbohydrate fluctuations during fermentative growth. Dephosphorylation occurs in >2 min after glucose withdrawal but the effect is reversed rapidly by refeeding with glucose. This response to glucose depletion is due to changes in cAPK activity rather than an increase in protein phosphatase activity. Surprisingly, the classical glucose-sensing systems are not connected to this rapid response system. Our results further imply that generic stress signals do not cause short-term depressions in cAPK activity. They operate on Msn2 by affecting an Msn5-dependent nuclear export and/or retention mechanism. PMID:11782433

NRC antitrust licensing actions, 1978--1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayer, S.J.; Simpson, J.J.

NUREG-0447, Antitrust Review of Nuclear Power Plants, was published in May 1978 and includes a compilation and discussion of U.S. Nuclear Regulatory Commission (NRC) proceedings and activity involving the NRC`s competitive review program through February 1978, NUREG-0447 is an update of an earlier discussion of the NRC`s antitrust review of nuclear power plants, NR-AIG-001, The US Nuclear Regulatory Commission`s Antitrust Review of Nuclear Power Plants: The Conditioning of Licenses, which reviewed the Commission`s antitrust review function from its inception in December 1970 through April 1976. This report summarizes the support provided to NRC staff in updating the compilation of themore » NRC`s antitrust licensing review activities for commercial nuclear power plants that have occurred since February 1978. 4 refs., 4 tabs.« less

CDKL5 influences RNA splicing activity by its association to the nuclear speckle molecular machinery.

PubMed

Ricciardi, Sara; Kilstrup-Nielsen, Charlotte; Bienvenu, Thierry; Jacquette, Aurélia; Landsberger, Nicoletta; Broccoli, Vania

2009-12-01

Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause severe neurodevelopmental disorders including infantile spasms, encephalopathy, West-syndrome and an early-onset variant of Rett syndrome. CDKL5 is a serine/threonine kinase whose involvement in Rett syndrome can be inferred by its ability to directly bind and mediate phosphorylation of MeCP2. However, it remains to be elucidated how CDKL5 exerts its function. Here, we report that CDKL5 localizes to specific nuclear foci referred to as nuclear speckles in both cell lines and tissues. These sub-nuclear structures are traditionally considered as storage/modification sites of pre-mRNA splicing factors. Interestingly, we provide evidence that CDKL5 regulates the dynamic behaviour of nuclear speckles. Indeed, CDKL5 overexpression leads to nuclear speckle disassembly, and this event is strictly dependent on its kinase activity. Conversely, its down-regulation affects nuclear speckle morphology leading to abnormally large and uneven speckles. Similar results were obtained for primary adult fibroblasts isolated from CDKL5-mutated patients. Altogether, these findings indicate that CDKL5 controls nuclear speckle morphology probably by regulating the phosphorylation state of splicing regulatory proteins. Nuclear speckles are dynamic sites that can continuously supply splicing factors to active transcription sites, where splicing occurs. Notably, we proved that CDKL5 influences alternative splicing, at least as proved in heterologous minigene assays. In conclusion, we provide evidence that CDKL5 is involved indirectly in pre-mRNA processing, by controlling splicing factor dynamics. These findings identify a biological process whose disregulation might affect neuronal maturation and activity in CDKL5-related disorders.

Acute Liver Injury Induces Nucleocytoplasmic Redistribution of Hepatic Methionine Metabolism Enzymes

PubMed Central

Delgado, Miguel; Garrido, Francisco; Pérez-Miguelsanz, Juliana; Pacheco, María; Partearroyo, Teresa; Pérez-Sala, Dolores

2014-01-01

Abstract Aims: The discovery of methionine metabolism enzymes in the cell nucleus, together with their association with key nuclear processes, suggested a putative relationship between alterations in their subcellular distribution and disease. Results: Using the rat model of d-galactosamine intoxication, severe changes in hepatic steady-state mRNA levels were found; the largest decreases corresponded to enzymes exhibiting the highest expression in normal tissue. Cytoplasmic protein levels, activities, and metabolite concentrations suffered more moderate changes following a similar trend. Interestingly, galactosamine treatment induced hepatic nuclear accumulation of methionine adenosyltransferase (MAT) α1 and S-adenosylhomocysteine hydrolase tetramers, their active assemblies. In fact, galactosamine-treated livers showed enhanced nuclear MAT activity. Acetaminophen (APAP) intoxication mimicked most galactosamine effects on hepatic MATα1, including accumulation of nuclear tetramers. H35 cells that overexpress tagged-MATα1 reproduced the subcellular distribution observed in liver, and the changes induced by galactosamine and APAP that were also observed upon glutathione depletion by buthionine sulfoximine. The H35 nuclear accumulation of tagged-MATα1 induced by these agents correlated with decreased glutathione reduced form/glutathione oxidized form ratios and was prevented by N-acetylcysteine (NAC) and glutathione ethyl ester. However, the changes in epigenetic modifications associated with tagged-MATα1 nuclear accumulation were only prevented by NAC in galactosamine-treated cells. Innovation: Cytoplasmic and nuclear changes in proteins that regulate the methylation index follow opposite trends in acute liver injury, their nuclear accumulation showing potential as disease marker. Conclusion: Altogether these results demonstrate galactosamine- and APAP-induced nuclear accumulation of methionine metabolism enzymes as active oligomers and unveil the implication of redox-dependent mechanisms in the control of MATα1 subcellular distribution. Antioxid. Redox Signal. 20, 2541–2554. PMID:24124652

Progress in space nuclear reactor power systems technology development - The SP-100 program

NASA Technical Reports Server (NTRS)

Davis, H. S.

1984-01-01

Activities related to the development of high-temperature compact nuclear reactors for space applications had reached a comparatively high level in the U.S. during the mid-1950s and 1960s, although only one U.S. nuclear reactor-powered spacecraft was actually launched. After 1973, very little effort was devoted to space nuclear reactor and propulsion systems. In February 1983, significant activities toward the development of the technology for space nuclear reactor power systems were resumed with the SP-100 Program. Specific SP-100 Program objectives are partly related to the determination of the potential performance limits for space nuclear power systems in 100-kWe and 1- to 100-MW electrical classes. Attention is given to potential missions and applications, regimes of possible space power applicability, safety considerations, conceptual system designs, the establishment of technical feasibility, nuclear technology, materials technology, and prospects for the future.

76 FR 32379 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-06

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2011-0114] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission (NRC). ACTION: Notice of pending...: Applications for licenses are [[Page 32380

NASA safety program activities in support of the Space Exploration Initiatives Nuclear Propulsion program

NASA Technical Reports Server (NTRS)

Sawyer, J. C., Jr.

1993-01-01

The activities of the joint NASA/DOE/DOD Nuclear Propulsion Program Technical Panels have been used as the basis for the current development of safety policies and requirements for the Space Exploration Initiatives (SEI) Nuclear Propulsion Technology development program. The Safety Division of the NASA Office of Safety and Mission Quality has initiated efforts to develop policies for the safe use of nuclear propulsion in space through involvement in the joint agency Nuclear Safety Policy Working Group (NSPWG), encouraged expansion of the initial policy development into proposed programmatic requirements, and suggested further expansion into the overall risk assessment and risk management process for the NASA Exploration Program. Similar efforts are underway within the Department of Energy to ensure the safe development and testing of nuclear propulsion systems on Earth. This paper describes the NASA safety policy related to requirements for the design of systems that may operate where Earth re-entry is a possibility. The expected plan of action is to support and oversee activities related to the technology development of nuclear propulsion in space, and support the overall safety and risk management program being developed for the NASA Exploration Program.

Rattling Nucleons: New Developments in Active Interrogation of Special Nuclear Material

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robert C. Runkle; David L. Chichester; Scott J. Thompson

2012-01-01

Active interrogation is a vigorous area of research and development due to its promise of offering detection and characterization capabilities of special nuclear material in environments where passive detection fails. The primary value added by active methods is the capability to penetrate shielding - special nuclear material itself, incidental materials, or intentional shielding - and advocates hope that active interrogation will provide a solution to the problem of detecting shielded uranium, which is at present the greatest obstacle to interdiction efforts. The technique also provides a unique benefit for quantifying nuclear material in high background-radiation environments, an area important formore » nuclear material safeguards and material accountancy. Progress has been made in the field of active interrogation on several fronts, most notably in the arenas of source development, systems integration, and the integration and exploitation of multiple fission and non-fission signatures. But penetration of interrogating radiation often comes at a cost, not only in terms of finance and dose but also in terms of induced backgrounds, system complexity, and extended measurement times (including set up and acquisition). These costs make the calculus for deciding to implement active interrogation more subtle than may be apparent. The purpose of this review is thus to examine existing interrogation methods, compare and contrast their attributes and limitations, and identify missions where active interrogation may hold the most promise.« less

Rattling nucleons: New developments in active interrogation of special nuclear material

NASA Astrophysics Data System (ADS)

Runkle, Robert C.; Chichester, David L.; Thompson, Scott J.

2012-01-01

Active interrogation is a vigorous area of research and development due to its promise of offering detection and characterization capabilities of special nuclear material in environments where passive detection fails. The primary value added by active methods is the capability to penetrate shielding—special nuclear material itself, incidental materials, or intentional shielding—and advocates hope that active interrogation will provide a solution to the problem of detecting shielded uranium, which is at present the greatest obstacle to interdiction efforts. The technique also provides a unique benefit for quantifying nuclear material in high background-radiation environments, an area important for nuclear material safeguards and material accountancy. Progress has been made in the field of active interrogation on several fronts, most notably in the arenas of source development, systems integration, and the integration and exploitation of multiple fission and non-fission signatures. But penetration of interrogating radiation often comes at a cost, not only in terms of finance and dose but also in terms of induced backgrounds, system complexity, and extended measurement times (including set up and acquisition). These costs make the calculus for deciding to implement active interrogation more subtle than may be apparent. The purpose of this review is thus to examine existing interrogation methods, compare and contrast their attributes and limitations, and identify missions where active interrogation may hold the most promise.

National Center for Nuclear Security: The Nuclear Forensics Project (F2012)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klingensmith, A. L.

These presentation visuals introduce the National Center for Nuclear Security. Its chartered mission is to enhance the Nation’s verification and detection capabilities in support of nuclear arms control and nonproliferation through R&D activities at the NNSS. It has three focus areas: Treaty Verification Technologies, Nonproliferation Technologies, and Technical Nuclear Forensics. The objectives of nuclear forensics are to reduce uncertainty in the nuclear forensics process & improve the scientific defensibility of nuclear forensics conclusions when applied to nearsurface nuclear detonations. Research is in four key areas: Nuclear Physics, Debris collection and analysis, Prompt diagnostics, and Radiochemistry.

Nuclear Fuels.

ERIC Educational Resources Information Center

Nash, J. Thomas

1983-01-01

Trends in and factors related to the nuclear industry and nuclear fuel production are discussed. Topics addressed include nuclear reactors, survival of the U.S. uranium industry, production costs, budget cuts by the Department of Energy and U.S. Geological survey for resource studies, mining, and research/development activities. (JN)

Binding blocks: building the Universe one nucleus at a time

NASA Astrophysics Data System (ADS)

Diget, C. Aa; Pastore, A.; Leech, K.; Haylett, T.; Lock, S.; Sanders, T.; Shelley, M.; Willett, H. V.; Keegans, J.; Sinclair, L.; Simpson, E. C.; Binding Blocks Collaboration

2017-03-01

We present a new teaching and outreach activity based around the construction of a three-dimensional chart of isotopes using \\text{LEG}{{\\text{O}}\\circledR} bricks5. The activity, binding blocks, demonstrates nuclear and astrophysical processes through a seven-meter chart of all nuclear isotopes, built from over 26 000 \\text{LEG}{{\\text{O}}\\circledR} bricks. It integrates A-Level and GCSE curricula across areas of nuclear physics, astrophysics, and chemistry, including: nuclear decays (through the colours in the chart); nuclear binding energy (through tower heights); production of chemical elements in the cosmos; fusion processes in stars and fusion energy on Earth; as well as links to medical physics, particularly diagnostics and radiotherapy.

Direct observation of nanoparticle-cancer cell nucleus interactions.

PubMed

Dam, Duncan Hieu M; Lee, Jung Heon; Sisco, Patrick N; Co, Dick T; Zhang, Ming; Wasielewski, Michael R; Odom, Teri W

2012-04-24

We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultrafast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy.

Establishment of stem cell lines from nuclear transferred and parthenogenetically activated mouse oocytes for therapeutic cloning.

PubMed

Ju, Jin Young; Park, Chun Young; Gupta, Mukesh Kumar; Uhm, Sang Jun; Paik, Eun Chan; Ryoo, Zae Young; Cho, Youl Hee; Chung, Kil Saeng; Lee, Hoon Taek

2008-05-01

To establish embryonic stem cell lines from nuclear transfer of somatic cell nuclei isolated from the same oocyte donor and from parthenogenetic activation. The study also evaluated the effect of the micromanipulation procedure on the outcome of somatic cell nuclear transfer in mice. Randomized, prospective study. Hospital-based assisted reproductive technology laboratory. F(1) (C57BL/6 x 129P3/J) mice. Metaphase II-stage oocytes were either parthenogenetically activated or nuclear transferred with cumulus cell nuclei or parthenogenetically activated after a sham-manipulation procedure. Embryogenesis and embryonic stem cell establishment. The development rate to morula/blastocyst of nuclear transferred oocytes (27.9% +/- 5.9%) was significantly lower than that of the sham-manipulated (84.1% +/- 5.6%) or parthenogenetic (98.6% +/- 1.4%) groups. A sharp decrease in cleavage potential was obvious in the two- to four-cell transition for the nuclear transferred embryos (79.0% +/- 4.6% and 43.3% +/- 5.0%), implying incomplete nuclear reprogramming in arrested oocytes. However, the cleavage, as well as the development rate, of parthenogenetic and sham-manipulated groups did not differ significantly. The embryonic stem cell line establishment rate was higher from parthenogenetically activated oocytes (15.7%) than nuclear transferred (4.3%) or sham-manipulated oocytes (12.5%). Cell colonies from all groups displayed typical morphology of mice embryonic stem cells and could be maintained successfully with undifferentiated morphology after continuous proliferation for more than 120 passages still maintaining normal karyotype. All these cells were positive for mice embryonic stem cell markers such as Oct-4 and SSEA-1 based on immunocytochemistry and reverse transcriptase-polymerase chain reaction. The clonal origin of the ntES cell line and the parthenogenetic embryonic stem cell lines were confirmed by polymerase chain reaction analysis of the polymorphic markers. Blastocyst injection experiments demonstrated that these lines contributed to resulting chimeras and are germ-line competent. We report the establishment of ntES cell lines from somatic cells isolated from same individual. Our data also suggest that embryo micromanipulation procedure during the nuclear transfer procedure influences the developmental ability and embryonic stem cell establishment rate of nuclear transferred embryos.

Nuclear Import of the Retrotransposon Tf1 Is Governed by a Nuclear Localization Signal That Possesses a Unique Requirement for the FXFG Nuclear Pore Factor Nup124p

PubMed Central

Dang, Van-Dinh; Levin, Henry L.

2000-01-01

Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein. PMID:11003674

Nuclear import of the retrotransposon Tf1 is governed by a nuclear localization signal that possesses a unique requirement for the FXFG nuclear pore factor Nup124p.

PubMed

Dang, V D; Levin, H L

2000-10-01

Retroviruses, such as human immunodeficiency virus, that infect nondividing cells generate integration precursors that must cross the nuclear envelope to reach the host genome. As a model for retroviruses, we investigated the nuclear entry of Tf1, a long-terminal-repeat-containing retrotransposon of the fission yeast Schizosaccharomyces pombe. Because the nuclear envelope of yeasts remains intact throughout the cell cycle, components of Tf1 must be transported through the envelope before integration can occur. The nuclear localization of the Gag protein of Tf1 is different from that of other proteins tested in that it has a specific requirement for the FXFG nuclear pore factor, Nup124p. Using extensive mutagenesis, we found that Gag contained three nuclear localization signals (NLSs) which, when included individually in a heterologous protein, were sufficient to direct nuclear import. In the context of the intact transposon, mutations in the NLS that mapped to the first 10 amino acid residues of Gag significantly impaired Tf1 retrotransposition and abolished nuclear localization of Gag. Interestingly, this NLS activity in the heterologous protein was specifically dependent upon the presence of Nup124p. Deletion analysis of heterologous proteins revealed the surprising result that the residues in Gag with the NLS activity were independent from the residues that conveyed the requirement for Nup124p. In fact, a fragment of Gag that lacked NLS activity, residues 10 to 30, when fused to a heterologous protein, was sufficient to cause the classical NLS of simian virus 40 to require Nup124p for nuclear import. Within the context of the current understanding of nuclear import, these results represent the novel case of a short amino acid sequence that specifies the need for a particular nuclear pore complex protein.

Activating the nuclear piston mechanism of 3D migration in tumor cells

PubMed Central

2017-01-01

Primary human fibroblasts have the remarkable ability to use their nucleus like a piston, switching from low- to high-pressure protrusions in response to the surrounding three-dimensional (3D) matrix. Although migrating tumor cells can also change how they migrate in response to the 3D matrix, it is not clear if they can switch between high- and low-pressure protrusions like primary fibroblasts. We report that unlike primary fibroblasts, the nuclear piston is not active in fibrosarcoma cells. Protease inhibition rescued the nuclear piston mechanism in polarized HT1080 and SW684 cells and generated compartmentalized pressure. Achieving compartmentalized pressure required the nucleoskeleton–cytoskeleton linker protein nesprin 3, actomyosin contractility, and integrin-mediated adhesion, consistent with lobopodia-based fibroblast migration. In addition, this activation of the nuclear piston mechanism slowed the 3D movement of HT1080 cells. Together, these data indicate that inhibiting protease activity during polarized tumor cell 3D migration is sufficient to restore the nuclear piston migration mechanism with compartmentalized pressure characteristic of nonmalignant cells. PMID:27998990

The ubiquitin ligase MuRF1 regulates PPARα activity in the heart by enhancing nuclear export via monoubiquitination

PubMed Central

Rodríguez, Jessica E.; Liao, Jie-Ying; He, Jun; Schisler, Jonathan C.; Newgard, Christopher B.; Drujan, Doreen; Glass, David L.; Frederick, C.Brandon; Yoder, Bryan C.; Lalush, David S.; Patterson, Cam; Willis, Monte S.

2015-01-01

The transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) α by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARα, but not PPARβ/δ or PPARγ in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARα activity and acyl-carnitine intermediates, while MuRF1−/− hearts exhibited increased PPARα activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARα, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARα, along with three specific lysines (292, 310, 388) required for MuRF1s targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARα, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure. PMID:26116825

Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage.

PubMed

Solozobova, Valeriya; Rolletschek, Alexandra; Blattner, Christine

2009-06-17

P53 is a key tumor suppressor protein. In response to DNA damage, p53 accumulates to high levels in differentiated cells and activates target genes that initiate cell cycle arrest and apoptosis. Since stem cells provide the proliferative cell pool within organisms, an efficient DNA damage response is crucial. In proliferating embryonic stem cells, p53 is localized predominantly in the cytoplasm. DNA damage-induced nuclear accumulation of p53 in embryonic stem cells activates transcription of the target genes mdm2, p21, puma and noxa. We observed bi-phasic kinetics for nuclear accumulation of p53 after ionizing radiation. During the first wave of nuclear accumulation, p53 levels were increased and the p53 target genes mdm2, p21 and puma were transcribed. Transcription of noxa correlated with the second wave of nuclear accumulation. Transcriptional activation of p53 target genes resulted in an increased amount of proteins with the exception of p21. While p21 transcripts were efficiently translated in 3T3 cells, we failed to see an increase in p21 protein levels after IR in embryonal stem cells. In embryonic stem cells where (anti-proliferative) p53 activity is not necessary, or even unfavorable, p53 is retained in the cytoplasm and prevented from activating its target genes. However, if its activity is beneficial or required, p53 is allowed to accumulate in the nucleus and activates its target genes, even in embryonic stem cells.

Annual Report To Congress. Department of Energy Activities Relating to the Defense Nuclear Facilities Safety Board, Calendar Year 2003

DOE Office of Scientific and Technical Information (OSTI.GOV)

None, None

2004-02-28

The Department of Energy (Department) submits an Annual Report to Congress each year detailing the Department’s activities relating to the Defense Nuclear Facilities Safety Board (Board), which provides advice and recommendations to the Secretary of Energy (Secretary) regarding public health and safety issues at the Department’s defense nuclear facilities. In 2003, the Department continued ongoing activities to resolve issues identified by the Board in formal recommendations and correspondence, staff issue reports pertaining to Department facilities, and public meetings and briefings. Additionally, the Department is implementing several key safety initiatives to address and prevent safety issues: safety culture and review ofmore » the Columbia accident investigation; risk reduction through stabilization of excess nuclear materials; the Facility Representative Program; independent oversight and performance assurance; the Federal Technical Capability Program (FTCP); executive safety initiatives; and quality assurance activities. The following summarizes the key activities addressed in this Annual Report.« less

77 FR 49833 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-17

... with States at Commercial Nuclear Power Plants and Other Nuclear Production and Utilization Facilities... or asked to report: Nuclear Power Plant Licensees, Materials Security Licensees and those States... and interested in monitoring the safety status of nuclear power plants and radioactive materials. This...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 9 2014-10-01 2014-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 9 2011-10-01 2011-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 9 2013-10-01 2013-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

78 FR 69648 - Civil Nuclear Trade Advisory Committee (CINTAC) Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... DEPARTMENT OF COMMERCE International Trade Administration Civil Nuclear Trade Advisory Committee... nuclear goods and services in accordance with applicable U.S. laws and regulations, including advice on how U.S. civil nuclear goods and services export policies, programs, and activities will affect the U...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

49 CFR 1580.111 - Harmonization of federal regulation of nuclear facilities.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 9 2012-10-01 2012-10-01 false Harmonization of federal regulation of nuclear facilities. 1580.111 Section 1580.111 Transportation Other Regulations Relating to Transportation (Continued... regulation of nuclear facilities. TSA will coordinate activities under this subpart with the Nuclear...

The Nuclear Signaling of NF-κB – Current Knowledge, New Insights, and Future Perspectives

PubMed Central

Wan, Fengyi; Lenardo, Michael J.

2011-01-01

The nuclear factor-kappa B (NF-κB) transcription factor plays a critical role in diverse cellular processes associated with proliferation, cell death, development, as well as innate and adaptive immune responses. NF-κB is normally sequestered in the cytoplasm by a family of inhibitory proteins known as IκBs. The signal pathways leading to the liberation and nuclear accumulation of NF-κB, which can be activated by a wide variety of stimuli, have been extensively studied in the past two decades. After gaining access to the nucleus, NF-κB must be actively regulated to execute its fundamental function as a transcription factor. Recent studies have highlighted the importance of nuclear signaling in the regulation of NF-κB transcriptional activity. A non-Rel subunit of NF-κB, ribosomal protein S3 (RPS3), and numerous other nuclear regulators of NF-κB including Akirin, Nurr1, SIRT6, and others, have recently been identified, unveiling novel and exciting layers of regulatory specificity for NF-κB in the nucleus. Further insights into the nuclear events that govern NF-κB function will deepen our understanding of the elegant control of its transcriptional activity and better inform the potential rational design of therapeutics for NF-κB-associated diseases. PMID:19997086

The detection of bulk explosives using nuclear-based techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgado, R.E.; Gozani, T.; Seher, C.C.

1988-01-01

In 1986 we presented a rationale for the detection of bulk explosives based on nuclear techniques that addressed the requirements of civil aviation security in the airport environment. Since then, efforts have intensified to implement a system based on thermal neutron activation (TNA), with new work developing in fast neutron and energetic photon reactions. In this paper we will describe these techniques and present new results from laboratory and airport testing. Based on preliminary results, we contended in our earlier paper that nuclear-based techniques did provide sufficiently penetrating probes and distinguishable detectable reaction products to achieve the FAA operational goals;more » new data have supported this contention. The status of nuclear-based techniques for the detection of bulk explosives presently under investigation by the US Federal Aviation Administration (FAA) is reviewed. These include thermal neutron activation (TNA), fast neutron activation (FNA), the associated particle technique, nuclear resonance absorption, and photoneutron activation. The results of comprehensive airport testing of the TNA system performed during 1987-88 are summarized. From a technical point of view, nuclear-based techniques now represent the most comprehensive and feasible approach for meeting the operational criteria of detection, false alarms, and throughput. 9 refs., 5 figs., 2 tabs.« less

Regulation of SIRT 1 mediated NAD dependent deacetylation: A novel role for the multifunctional enzyme CD38

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aksoy, Pinar; Escande, Carlos; Seccion Biologia Celular, Facultad de Ciencias, Universidad de la Republica, Igua 4225, Montevideo

2006-10-13

The SIRT 1 enzyme is a NAD dependent deacetylase implicated in ageing, cell protection, and energy metabolism in mammalian cells. How the endogenous activity of SIRT 1 is modulated is not known. The enzyme CD38 is a multifunctional enzyme capable of synthesis of the second messenger, cADPR, NAADP, and ADPR. However, the major enzymatic activity of CD38 is the hydrolysis of NAD. Of particular interest is the fact that CD38 is present on the inner nuclear membrane. Here, we investigate the modulation of the SIRT 1 activity by CD38. We propose that by modulating availability of NAD to the SIRT1more » enzyme, CD38 may regulate SIRT1 enzymatic activity. We observed that in CD38 knockout mice, tissue levels of NAD are significantly increased. We also observed that incubation of purified recombinant SIRT1 enzyme with CD38 or nuclear extracts of wild-type mice led to a significant inhibition of its activity. In contrast, incubation of SIRT1 with cellular extract from CD38 knockout mice was without effect. Furthermore, the endogenous activity of SIRT1 was several time higher in nuclear extracts from CD38 knockout mice when compared to wild-type nuclear extracts. Finally, the in vivo deacetylation of the SIRT1 substrate P53 is increased in CD38 knockout mice tissue. Our data support the novel concept that nuclear CD38 is a major regulator of cellular/nuclear NAD level, and SIRT1 activity. These findings have strong implications for understanding the basic mechanisms that modulate intracellular NAD levels, energy homeostasis, as well as ageing and cellular protection modulated by the SIRT enzymes.« less

Med1 subunit of the mediator complex in nuclear receptor-regulated energy metabolism, liver regeneration, and hepatocarcinogenesis.

PubMed

Jia, Yuzhi; Viswakarma, Navin; Reddy, Janardan K

2014-01-01

Several nuclear receptors regulate diverse metabolic functions that impact on critical biological processes, such as development, differentiation, cellular regeneration, and neoplastic conversion. In the liver, some members of the nuclear receptor family, such as peroxisome proliferator-activated receptors (PPARs), constitutive androstane receptor (CAR), farnesoid X receptor (FXR), liver X receptor (LXR), pregnane X receptor (PXR), glucocorticoid receptor (GR), and others, regulate energy homeostasis, the formation and excretion of bile acids, and detoxification of xenobiotics. Excess energy burning resulting from increases in fatty acid oxidation systems in liver generates reactive oxygen species, and the resulting oxidative damage influences liver regeneration and liver tumor development. These nuclear receptors are important sensors of exogenous activators as well as receptor-specific endogenous ligands. In this regard, gene knockout mouse models revealed that some lipid-metabolizing enzymes generate PPARα-activating ligands, while others such as ACOX1 (fatty acyl-CoA oxidase1) inactivate these endogenous PPARα activators. In the absence of ACOX1, the unmetabolized ACOX1 substrates cause sustained activation of PPARα, and the resulting increase in energy burning leads to hepatocarcinogenesis. Ligand-activated nuclear receptors recruit the multisubunit Mediator complex for RNA polymerase II-dependent gene transcription. Evidence indicates that the Med1 subunit of the Mediator is essential for PPARα, PPARγ, CAR, and GR signaling in liver. Med1 null hepatocytes fail to respond to PPARα activators in that these cells do not show induction of peroxisome proliferation and increases in fatty acid oxidation enzymes. Med1-deficient hepatocytes show no increase in cell proliferation and do not give rise to liver tumors. Identification of nuclear receptor-specific coactivators and Mediator subunits should further our understanding of the complexities of metabolic diseases associated with increased energy combustion in liver.

SKP2- and OTUD1-regulated non-proteolytic ubiquitination of YAP promotes YAP nuclear localization and activity.

PubMed

Yao, Fan; Zhou, Zhicheng; Kim, Jongchan; Hang, Qinglei; Xiao, Zhenna; Ton, Baochau N; Chang, Liang; Liu, Na; Zeng, Liyong; Wang, Wenqi; Wang, Yumeng; Zhang, Peijing; Hu, Xiaoyu; Su, Xiaohua; Liang, Han; Sun, Yutong; Ma, Li

2018-06-11

Dysregulation of YAP localization and activity is associated with pathological conditions such as cancer. Although activation of the Hippo phosphorylation cascade is known to cause cytoplasmic retention and inactivation of YAP, emerging evidence suggests that YAP can be regulated in a Hippo-independent manner. Here, we report that YAP is subject to non-proteolytic, K63-linked polyubiquitination by the SCF SKP2 E3 ligase complex (SKP2), which is reversed by the deubiquitinase OTUD1. The non-proteolytic ubiquitination of YAP enhances its interaction with its nuclear binding partner TEAD, thereby inducing YAP's nuclear localization, transcriptional activity, and growth-promoting function. Independently of Hippo signaling, mutation of YAP's K63-linkage specific ubiquitination sites K321 and K497, depletion of SKP2, or overexpression of OTUD1 retains YAP in the cytoplasm and inhibits its activity. Conversely, overexpression of SKP2 or loss of OTUD1 leads to nuclear localization and activation of YAP. Altogether, our study sheds light on the ubiquitination-mediated, Hippo-independent regulation of YAP.

Reduction of nuclear encoded enzymes of mitochondrial energy metabolism in cells devoid of mitochondrial DNA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mueller, Edith E., E-mail: ed.mueller@salk.at; Mayr, Johannes A., E-mail: h.mayr@salk.at; Zimmermann, Franz A., E-mail: f.zimmermann@salk.at

2012-01-20

Highlights: Black-Right-Pointing-Pointer We examined OXPHOS and citrate synthase enzyme activities in HEK293 cells devoid of mtDNA. Black-Right-Pointing-Pointer Enzymes partially encoded by mtDNA show reduced activities. Black-Right-Pointing-Pointer Also the entirely nuclear encoded complex II and citrate synthase exhibit reduced activities. Black-Right-Pointing-Pointer Loss of mtDNA induces a feedback mechanism that downregulates complex II and citrate synthase. -- Abstract: Mitochondrial DNA (mtDNA) depletion syndromes are generally associated with reduced activities of oxidative phosphorylation (OXPHOS) enzymes that contain subunits encoded by mtDNA. Conversely, entirely nuclear encoded mitochondrial enzymes in these syndromes, such as the tricarboxylic acid cycle enzyme citrate synthase (CS) and OXPHOS complexmore » II, usually exhibit normal or compensatory enhanced activities. Here we report that a human cell line devoid of mtDNA (HEK293 {rho}{sup 0} cells) has diminished activities of both complex II and CS. This finding indicates the existence of a feedback mechanism in {rho}{sup 0} cells that downregulates the expression of entirely nuclear encoded components of mitochondrial energy metabolism.« less

A Highly Organized Structure Mediating Nuclear Localization of a Myb2 Transcription Factor in the Protozoan Parasite Trichomonas vaginalis ▿ †

PubMed Central

Chu, Chien-Hsin; Chang, Lung-Chun; Hsu, Hong-Ming; Wei, Shu-Yi; Liu, Hsing-Wei; Lee, Yu; Kuo, Chung-Chi; Indra, Dharmu; Chen, Chinpan; Ong, Shiou-Jeng; Tai, Jung-Hsiang

2011-01-01

Nuclear proteins usually contain specific peptide sequences, referred to as nuclear localization signals (NLSs), for nuclear import. These signals remain unexplored in the protozoan pathogen, Trichomonas vaginalis. The nuclear import of a Myb2 transcription factor was studied here using immunodetection of a hemagglutinin-tagged Myb2 overexpressed in the parasite. The tagged Myb2 was localized to the nucleus as punctate signals. With mutations of its polybasic sequences, 48KKQK51 and 61KR62, Myb2 was localized to the nucleus, but the signal was diffusive. When fused to a C-terminal non-nuclear protein, the Myb2 sequence spanning amino acid (aa) residues 48 to 143, which is embedded within the R2R3 DNA-binding domain (aa 40 to 156), was essential and sufficient for efficient nuclear import of a bacterial tetracycline repressor (TetR), and yet the transport efficiency was reduced with an additional fusion of a firefly luciferase to TetR, while classical NLSs from the simian virus 40 T-antigen had no function in this assay system. Myb2 nuclear import and DNA-binding activity were substantially perturbed with mutation of a conserved isoleucine (I74) in helix 2 to proline that altered secondary structure and ternary folding of the R2R3 domain. Disruption of DNA-binding activity alone by point mutation of a lysine residue, K51, preceding the structural domain had little effect on Myb2 nuclear localization, suggesting that nuclear translocation of Myb2, which requires an ordered structural domain, is independent of its DNA binding activity. These findings provide useful information for testing whether myriad Mybs in the parasite use a common module to regulate nuclear import. PMID:22021237

10 CFR 784.6 - National security considerations for waiver of certain sensitive inventions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... or under any Government contract or subcontract of the Naval Nuclear Propulsion Program or the nuclear weapons programs or other atomic energy defense activities of the Department of Energy, a...) under the Naval Nuclear Propulsion Program or the nuclear weapons programs or other atomic energy...

10 CFR 784.6 - National security considerations for waiver of certain sensitive inventions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... or under any Government contract or subcontract of the Naval Nuclear Propulsion Program or the nuclear weapons programs or other atomic energy defense activities of the Department of Energy, a...) under the Naval Nuclear Propulsion Program or the nuclear weapons programs or other atomic energy...

Nuclear Strategy and World Order: The United States Imperative.

ERIC Educational Resources Information Center

Beres, Louis Rene

The current U.S. nuclear strategy goes beyond the legitimate objective of survivable strategic forces to active preparation for nuclear war. The Reagan administration strategy rejects minimum deterrence and prepares for a nuclear war that might be protracted and controlled. The strategy reflects the understanding that a combination of counterforce…

76 FR 4646 - Blue Ribbon Commission on America's Nuclear Future

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

.... ADDRESSES: Navy Shipyard, 1333 Isaac Hull Avenue, SE., Washington, DC 20376. FOR FURTHER INFORMATION CONTACT... spent nuclear fuel and nuclear waste. The Commission is scheduled to submit a draft report to the..., high-level waste, and materials derived from nuclear activities.'' In support of that effort, the...

Special nuclear materials cutoff exercise: Issues and lessons learned. Volume 3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Libby, R.A.; Segal, J.E.; Stanbro, W.D.

1995-08-01

This document is appendices D-J for the Special Nuclear Materials Cutoff Exercise: Issues and Lessons Learned. Included are discussions of the US IAEA Treaty, safeguard regulations for nuclear materials, issue sheets for the PUREX process, and the LANL follow up activity for reprocessing nuclear materials.

Rover nuclear rocket engine program: Overview of rover engine tests

NASA Technical Reports Server (NTRS)

Finseth, J. L.

1991-01-01

The results of nuclear rocket development activities from the inception of the ROVER program in 1955 through the termination of activities on January 5, 1973 are summarized. This report discusses the nuclear reactor test configurations (non cold flow) along with the nuclear furnace demonstrated during this time frame. Included in the report are brief descriptions of the propulsion systems, test objectives, accomplishments, technical issues, and relevant test results for the various reactor tests. Additionally, this document is specifically aimed at reporting performance data and their relationship to fuel element development with little or no emphasis on other (important) items.

Rare sugar D-allose strongly induces thioredoxin-interacting protein and inhibits osteoclast differentiation in Raw264 cells.

PubMed

Yamada, Kana; Noguchi, Chisato; Kamitori, Kazuyo; Dong, Youyi; Hirata, Yuko; Hossain, Mohammad A; Tsukamoto, Ikuko; Tokuda, Masaaki; Yamaguchi, Fuminori

2012-02-01

Oxidative stress modulates the osteoclast differentiation via redox systems, and thioredoxin 1 (Trx) promotes the osteoclast formation by regulating the activity of transcription factors. The function of Trx is known to be regulated by its binding partner, thioredoxin-interacting protein (TXNIP). We previously reported that the expression of TXNIP gene is strongly induced by a rare sugar D-allose. In this study, we tested the hypothesis that D-allose could inhibit the osteoclast differentiation by regulating the Trx function. We used a murine Raw264 cell line that differentiates to the osteoclast by the receptor activator of nuclear factor-κB ligand (RANKL) treatment. The effect of sugars was evaluated by tartrate-resistant acid phosphatase staining. The expression and localization of TXNIP and Trx protein were examined by Western blotting and immunohistochemisty. The activity of the nuclear factor-κB, nuclear factor of activated T cells, and activator protein 1 transcription factors was measured by the luciferase reporter assay. The addition of D-allose (25 mmol/L) inhibited the osteoclast differentiation down to 9.53% ± 1.27% of a receptor activator of nuclear factor-κB ligand-only treatment. During the osteoclast differentiation, a significant increase of TNXIP was observed by D-allose treatment. The immunohistochemical analysis showed that both Trx and TXNIP existed in the nucleus in preosteoclasts and osteoclasts. Overexpression of TXNIP by plasmid transfection also inhibited the osteoclast formation, indicating the functional importance of TXNIP for the osteoclast differentiation. Transcriptional activity of the activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells, known to be modulated by Trx, were inhibited by D-allose. In conclusion, our data indicate that D-allose is a strong inhibitor of the osteoclast differentiation, and this effect could be caused by TXNIP induction and a resulting inhibition of the Trx function. Copyright © 2012 Elsevier Inc. All rights reserved.

Spatio-temporal modelling of the NF-κB intracellular signalling pathway: the roles of diffusion, active transport, and cell geometry.

PubMed

Terry, Alan J; Chaplain, Mark A J

2011-12-07

The nuclear factor kappa B (NF-κB) intracellular signalling pathway is central to many stressful, inflammatory, and innate immune responses. NF-κB proteins themselves are transcription factors for hundreds of genes. Experiments have shown that the NF-κB pathway can exhibit oscillatory dynamics-a negative feedback loop causes oscillatory nuclear-cytoplasmic translocation of NF-κB. Given that cell size and shape are known to influence intracellular signal transduction, we consider a spatio-temporal model of partial differential equations for the NF-κB pathway, where we model molecular movement by diffusion and, for several key species including NF-κB, by active transport as well. Through numerical simulations we find values for model parameters such that sustained oscillatory dynamics occur. Our spatial profiles and animations bear a striking resemblance to experimental images and movie clips employing fluorescent fusion proteins. We discover that oscillations in nuclear NF-κB may occur when active transport is across the nuclear membrane only, or when no species are subject to active transport. However, when active transport is across the nuclear membrane and NF-κB is additionally actively transported through the cytoplasm, oscillations are lost. Hence transport mechanisms in a cell will influence its response to activation of its NF-κB pathway. We also demonstrate that sustained oscillations in nuclear NF-κB are somewhat robust to changes in the shape of the cell, or the shape, location, and size of its nucleus, or the location of ribosomes. Yet if the cell is particularly flat or the nucleus sufficiently small, then oscillations are lost. Thus the geometry of a cell may partly determine its response to NF-κB activation. The NF-κB pathway is known to be constitutively active in several human cancers. Our spatially explicit modelling approach will allow us, in future work, to investigate targeted drug therapy of tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.

Active Neutron-Based Interrogation System with D-D Neutron Source for Detection of Special Nuclear Materials

NASA Astrophysics Data System (ADS)

Takahashi, Y.; Misawa, T.; Yagi, T.; Pyeon, C. H.; Kimura, M.; Masuda, K.; Ohgaki, H.

2015-10-01

The detection of special nuclear materials (SNM) is an important issue for nuclear security. The interrogation systems used in a sea port and an airport are developed in the world. The active neutron-based interrogation system is the one of the candidates. We are developing the active neutron-based interrogation system with a D-D fusion neutron source for the nuclear security application. The D-D neutron source is a compact discharge-type fusion neutron source called IEC (Inertial-Electrostatic Confinement fusion) device which provides 2.45 MeV neutrons. The nuclear materials emit the highenergy neutrons by fission reaction. High-energy neutrons with energies over 2.45 MeV amount to 30% of all the fission neutrons. By using the D-D neutron source, the detection of SNMs is considered to be possible with the attention of fast neutrons if there is over 2.45 MeV. Ideally, neutrons at En>2.45 MeV do not exist if there is no nuclear materials. The detection of fission neutrons over 2.45 MeV are hopeful prospect for the detection of SNM with a high S/N ratio. In the future, the experiments combined with nuclear materials and a D-D neutron source will be conducted. Furthermore, the interrogation system will be numerically investigated by using nuclear materials, a D-D neutron source, and a steel container.

The effects of dexamethasone on rat brain cortical nuclear factor kappa B (NF-{kappa}B) in endotoxic shock

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Zhi; Kang Jinsong; Li Yang

2006-08-01

To explore the molecular mechanism of brain tissue injury induced by lipopolysaccharide (LPS), we studied the effects of endotoxic shock on rat brain cortex NF-{kappa}B and the effects of dexamethasone on these changes. Rats were randomly divided into LPS, LPS + dexamethasone, and control groups. The DNA-binding activity of NF-{kappa}B was observed using electrophoretic mobility shift assay (EMSA). Protein expression in nuclear extracts was studied using Western blots, and nuclear translocation was observed using immunohistochemistry. These indices were assayed at 1 h and 4 h after intravenous injection of LPS (4 mg.kg{sup -1}). EMSA showed significantly increased NF-{kappa}B DNA-binding activitymore » in nuclear extracts from the LPS group at both 1 h and 4 h after LPS injection, compared with the control group (P < 0.01). For the LPS group, the NF-{kappa}B DNA-binding activity was greater at 1 h than at 4 h (P < 0.05). The expression of p65 and p50 protein in the nuclear extracts was also increased, as compared with the control group. However, the expression of p65 and p50 protein from cytosolic extracts did not show any significant change. Dexamethasone down-regulated not only NF-{kappa}B DNA-binding activity but also the expression of p65 protein in the nuclear extracts. From these data, we have concluded that NF-{kappa}B activation and nuclear translocation of NF-{kappa}B play a key role in the molecular mechanism of brain tissue injury in endotoxic shock. Dexamethasone may alleviate brain injury by inhibiting NF-{kappa}B activation.« less

Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome

PubMed Central

Turan, Kadir; Mibayashi, Masaki; Sugiyama, Kenji; Saito, Shoko; Numajiri, Akiko; Nagata, Kyosuke

2004-01-01

Mx proteins belong to the dynamin superfamily of high molecular weight GTPases and interfere with multiplication of a wide variety of viruses. Earlier studies show that nuclear mouse Mx1 and human MxA designed to be localized in the nucleus inhibit the transcription step of the influenza virus genome. Here we set a transient influenza virus transcription system using luciferase as a reporter gene and cells expressing the three RNA polymerase subunits, PB1, PB2 and PA, and NP. We used this reporter assay system and nuclear-localized MxA proteins to get clues for elucidating the anti-influenza virus activity of MxA. Nuclear-localized VP16-MxA and MxA-TAg NLS strongly interfered with the influenza virus transcription. Over-expression of PB2 led to a slight resumption of the transcription inhibition by nuclear MxA, whereas over-expression of PB1 and PA did not affect the MxA activity. Of interest is that the inhibitory activity of the nuclear MxA was markedly neutralized by over-expression of NP. An NP devoid of its C-terminal region, but containing the N-terminal RNA binding domain, also neutralized the VP16-MxA activity in a dose-dependent manner, whereas an NP lacking the N-terminal region did not affect the VP16-MxA activity. Further, not only VP16-MxA but also the wild-type MxA was found to interact with NP in influenza virus-infected cells. This indicates that the nuclear MxA suppresses the influenza virus transcription by interacting with not only PB2 but also NP. PMID:14752052

Direct Observation of Nanoparticle-Cancer Cell Nucleus Interactions

PubMed Central

Dam, Duncan Hieu M.; Lee, Jung Heon; Sisco, Patrick N.; Co, Dick T.; Zhang, Ming; Wasielewski, Michael R.; Odom, Teri W.

2012-01-01

We report the direct visualization of interactions between drug-loaded nanoparticles and the cancer cell nucleus. Nanoconstructs composed of nucleolin-specific aptamers and gold nanostars were actively transported to the nucleus and induced major changes to the nuclear phenotype via nuclear envelope invaginations near the site of the construct. The number of local deformations could be increased by ultra-fast, light-triggered release of the aptamers from the surface of the gold nanostars. Cancer cells with more nuclear envelope folding showed increased caspase 3 and 7 activity (apoptosis) as well as decreased cell viability. This newly revealed correlation between drug-induced changes in nuclear phenotype and increased therapeutic efficacy could provide new insight for nuclear-targeted cancer therapy. PMID:22424173

Nuclear Calcium Signaling Controls Expression of a Large Gene Pool: Identification of a Gene Program for Acquired Neuroprotection Induced by Synaptic Activity

PubMed Central

Zhang, Sheng-Jia; Zou, Ming; Lu, Li; Lau, David; Ditzel, Désirée A. W.; Delucinge-Vivier, Celine; Aso, Yoshinori; Descombes, Patrick; Bading, Hilmar

2009-01-01

Synaptic activity can boost neuroprotection through a mechanism that requires synapse-to-nucleus communication and calcium signals in the cell nucleus. Here we show that in hippocampal neurons nuclear calcium is one of the most potent signals in neuronal gene expression. The induction or repression of 185 neuronal activity-regulated genes is dependent upon nuclear calcium signaling. The nuclear calcium-regulated gene pool contains a genomic program that mediates synaptic activity-induced, acquired neuroprotection. The core set of neuroprotective genes consists of 9 principal components, termed Activity-regulated Inhibitor of Death (AID) genes, and includes Atf3, Btg2, GADD45β, GADD45γ, Inhibin β-A, Interferon activated gene 202B, Npas4, Nr4a1, and Serpinb2, which strongly promote survival of cultured hippocampal neurons. Several AID genes provide neuroprotection through a common process that renders mitochondria more resistant to cellular stress and toxic insults. Stereotaxic delivery of AID gene-expressing recombinant adeno-associated viruses to the hippocampus confers protection in vivo against seizure-induced brain damage. Thus, treatments that enhance nuclear calcium signaling or supplement AID genes represent novel therapies to combat neurodegenerative conditions and neuronal cell loss caused by synaptic dysfunction, which may be accompanied by a deregulation of calcium signal initiation and/or propagation to the cell nucleus. PMID:19680447

Nuclear Receptor Activity and Liver Cancer Lesion Progression

EPA Science Inventory

Nuclear receptors (NRs) are ligand-activated transcription factors that control diverse cellular processes. Chronic stimulation of some NRs is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. We explored this question using human CAR, PXR, PPARα,...

RADIOACTIVE WASTE MANAGEMENT IN THE CHERNOBYL EXCLUSION ZONE - 25 YEARS SINCE THE CHERNOBYL NUCLEAR POWER PLANT ACCIDENT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farfan, E.; Jannik, T.

2011-10-01

Radioactive waste management is an important component of the Chernobyl Nuclear Power Plant accident mitigation and remediation activities of the so-called Chernobyl Exclusion Zone. This article describes the localization and characteristics of the radioactive waste present in the Chernobyl Exclusion Zone and summarizes the pathways and strategy for handling the radioactive waste related problems in Ukraine and the Chernobyl Exclusion Zone, and in particular, the pathways and strategies stipulated by the National Radioactive Waste Management Program. The brief overview of the radioactive waste issues in the ChEZ presented in this article demonstrates that management of radioactive waste resulting from amore » beyond-designbasis accident at a nuclear power plant becomes the most challenging and the costliest effort during the mitigation and remediation activities. The costs of these activities are so high that the provision of radioactive waste final disposal facilities compliant with existing radiation safety requirements becomes an intolerable burden for the current generation of a single country, Ukraine. The nuclear accident at the Fukushima-1 NPP strongly indicates that accidents at nuclear sites may occur in any, even in a most technologically advanced country, and the Chernobyl experience shows that the scope of the radioactive waste management activities associated with the mitigation of such accidents may exceed the capabilities of a single country. Development of a special international program for broad international cooperation in accident related radioactive waste management activities is required to handle these issues. It would also be reasonable to consider establishment of a dedicated international fund for mitigation of accidents at nuclear sites, specifically, for handling radioactive waste problems in the ChEZ. The experience of handling Chernobyl radioactive waste management issues, including large volumes of radioactive soils and complex structures of fuel containing materials can be fairly useful for the entire world's nuclear community and can help make nuclear energy safer.« less

Extra-Territorial Siting of Nuclear Installations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shea, Thomas E.; Morris, Frederic A.

2009-10-07

Arrangements might be created for siting nuclear installations on land ceded by a host State for administration by an international or multinational organization. Such arrangements might prove useful in terms of resolving suspicions of proliferation in troubled areas of the world, or as a means to introduce nuclear activities into areas where political, financial or technical capabilities might otherwise make such activities unsound, or as a means to enable global solutions to be instituted for major nuclear concerns (e.g., spent fuel management). The paper examines practical matters associated with the legal and programmatic aspects of siting nuclear installations, including diplomatic/politicalmore » frameworks, engaging competent industrial bodies, protection against seizure, regulation to ensure safety and security, waste management, and conditions related to the dissolution of the extra-territorial provisions as may be agreed as the host State(s) achieve the capabilities to own and operate the installations. The paper considers the potential for using such a mechanism across the spectrum of nuclear power activities, from mining to geological repositories for nuclear waste. The paper considers the non-proliferation dimensions associated with such arrangements, and the pros and cons affecting potential host States, technology vendor States, regional neighbors and the international community. It considers in brief potential applications in several locations today.« less

Hormone- and light-regulated nucleocytoplasmic transport in plants: current status.

PubMed

Lee, Yew; Lee, Hak-Soo; Lee, June-Seung; Kim, Seong-Ki; Kim, Soo-Hwan

2008-01-01

The gene regulation mechanisms underlying hormone- and light-induced signal transduction in plants rely not only on post-translational modification and protein degradation, but also on selective inclusion and exclusion of proteins from the nucleus. For example, plant cells treated with light or hormones actively transport many signalling regulatory proteins, transcription factors, and even photoreceptors and hormone receptors into the nucleus, while actively excluding other proteins. The nuclear envelope (NE) is the physical and functional barrier that mediates this selective partitioning, and nuclear transport regulators transduce hormone- or light-initiated signalling pathways across the membrane to mediate nuclear activities. Recent reports revealed that mutating the proteins regulating nuclear transport through the pores, such as nucleoporins, alters the plant's response to a stimulus. In this review, recent works are introduced that have revealed the importance of regulated nucleocytoplasmic partitioning. These important findings deepen our understanding about how co-ordinated plant hormone and light signal transduction pathways facilitate communication between the cytoplasm and the nucleus. The roles of nucleoporin components within the nuclear pore complex (NPC) are also emphasized, as well as nuclear transport cargo, such as Ran/TC4 and its binding proteins (RanBPs), in this process. Recent findings concerning these proteins may provide a possible direction by which to characterize the regulatory potential of hormone- or light-triggered nuclear transport.

YY1 Controls Immunoglobulin Class Switch Recombination and Nuclear Activation-Induced Deaminase Levels

PubMed Central

Zaprazna, Kristina

2012-01-01

Activation-induced deaminase (AID) is an enzyme required for class switch recombination (CSR) and somatic hypermutation (SHM), processes that ensure antibody maturation and expression of different immunoglobulin isotypes. AID function is tightly regulated by tissue- and stage-specific expression, nuclear localization, and protein stability. Transcription factor YY1 is crucial for early B cell development, but its function at late B cell stages is unknown. Here, we show that YY1 conditional knockout in activated splenic B cells interferes with CSR. Knockout of YY1 did not affect B cell proliferation, transcription of the AID and IgM genes, or levels of various switch region germ line transcripts. However, we show that YY1 physically interacts with AID and controls the accumulation of nuclear AID, at least in part, by increasing nuclear AID stability. We show for the first time that YY1 plays a novel role in CSR and controls nuclear AID protein levels. PMID:22290437

BXR, an embryonic orphan nuclear receptor activated by a novel class of endogenous benzoate metabolites

PubMed Central

Blumberg, Bruce; Kang, Heonjoong; Bolado, Jack; Chen, Hongwu; Craig, A. Grey; Moreno, Tanya A.; Umesono, Kazuhiko; Perlmann, Thomas; De Robertis, Eddy M.; Evans, Ronald M.

1998-01-01

Nuclear receptors are ligand-modulated transcription factors that respond to steroids, retinoids, and thyroid hormones to control development and body physiology. Orphan nuclear receptors, which lack identified ligands, provide a unique, and largely untapped, resource to discover new principles of physiologic homeostasis. We describe the isolation and characterization of the vertebrate orphan receptor, BXR, which heterodimerizes with RXR and binds high-affinity DNA sites composed of a variant thyroid hormone response element. A bioactivity-guided screen of embryonic extracts revealed that BXR is activatable by low-molecular-weight molecules with spectral patterns distinct from known nuclear receptor ligands. Mass spectrometry and 1H NMR analysis identified alkyl esters of amino and hydroxy benzoic acids as potent, stereoselective activators. In vitro cofactor association studies, along with competable binding of radiolabeled compounds, establish these molecules as bona fide ligands. Benzoates comprise a new molecular class of nuclear receptor ligand and their activity suggests that BXR may control a previously unsuspected vertebrate signaling pathway. PMID:9573044

Genome-Nuclear Lamina Interactions Regulate Cardiac Stem Cell Lineage Restriction.

PubMed

Poleshko, Andrey; Shah, Parisha P; Gupta, Mudit; Babu, Apoorva; Morley, Michael P; Manderfield, Lauren J; Ifkovits, Jamie L; Calderon, Damelys; Aghajanian, Haig; Sierra-Pagán, Javier E; Sun, Zheng; Wang, Qiaohong; Li, Li; Dubois, Nicole C; Morrisey, Edward E; Lazar, Mitchell A; Smith, Cheryl L; Epstein, Jonathan A; Jain, Rajan

2017-10-19

Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina. Deletion of Hdac3 in cardiac progenitor cells releases genomic regions from the nuclear periphery, leading to precocious cardiac gene expression and differentiation into cardiomyocytes; in contrast, restricting Hdac3 to the nuclear periphery rescues myogenesis in progenitors otherwise lacking Hdac3. Our results suggest that availability of genomic regions for activation by lineage-specific factors is regulated in part through dynamic chromatin-nuclear lamina interactions and that competence of a progenitor cell to respond to differentiation signals may depend upon coordinated movement of responding gene loci away from the nuclear periphery. Copyright © 2017 Elsevier Inc. All rights reserved.

The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets.

PubMed

Romanauska, Anete; Köhler, Alwin

2018-06-13

The inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. Here, we show that the INM is an adaptable membrane territory capable of lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets from the INM and is characterized by lipid exchange through Seipin-dependent membrane bridges. We identify the genetic circuit for nuclear lipid droplet synthesis and a role of these organelles in regulating this circuit by sequestration of a transcription factor. Our findings suggest a link between INM metabolism and genome regulation and have potential relevance for human lipodystrophy. Copyright © 2018 Elsevier Inc. All rights reserved.

The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.

PubMed

Silla, Toomas; Karadoulama, Evdoxia; Mąkosa, Dawid; Lubas, Michal; Jensen, Torben Heick

2018-05-15

Mammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA + ) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA + RNA foci with "pA-tail exosome targeting (PAXT) connection" components MTR4, ZFC3H1, and PABPN1 but no overlap with known nuclear structures such as Cajal bodies, speckles, paraspeckles, or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence, selected pA + RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear pA + RNA retention factor, counteracting nuclear export activity. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PAK1 translocates into nucleus in response to prolactin but not to estrogen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oladimeji, Peter, E-mail: Peter.Oladimeji@rockets.utoledo.edu; Diakonova, Maria, E-mail: mdiakon@utnet.utoledo.edu

2016-04-22

Tyrosyl phosphorylation of the p21-activated serine–threonine kinase 1 (PAK1) has an essential role in regulating PAK1 functions in breast cancer cells. We previously demonstrated that PAK1 serves as a common node for estrogen (E2)- and prolactin (PRL)-dependent pathways. We hypothesize herein that intracellular localization of PAK1 is affected by PRL and E2 treatments differently. We demonstrate by immunocytochemical analysis that PAK1 nuclear translocation is ligand-dependent: only PRL but not E2 stimulated PAK1 nuclear translocation. Tyrosyl phosphorylation of PAK1 is essential for this nuclear translocation because phospho-tyrosyl-deficient PAK1 Y3F mutant is retained in the cytoplasm in response to PRL. We confirmedmore » these data by Western blot analysis of subcellular fractions. In 30 min of PRL treatment, only 48% of pTyr-PAK1 is retained in the cytoplasm of PAK1 WT clone while 52% re-distributes into the nucleus and pTyr-PAK1 shuttles back to the cytoplasm by 60 min of PRL treatment. In contrast, PAK1 Y3F is retained in the cytoplasm. E2 treatment causes nuclear translocation of neither PAK1 WT nor PAK1 Y3F. Finally, we show by an in vitro kinase assay that PRL but not E2 stimulates PAK1 kinase activity in the nuclear fraction. Thus, PAK1 nuclear translocation is ligand-dependent: PRL activates PAK1 and induces translocation of activated pTyr-PAK1 into nucleus while E2 activates pTyr-PAK1 only in the cytoplasm. - Highlights: • Prolactin but not estrogen causes translocation of PAK1 into nucleus. • Tyrosyl phosphorylation of PAK1 is required for nuclear localization. • Prolactin but not estrogen stimulates PAK1 kinase activity in nucleus.« less

Nuclear Forensics for High School Science

NASA Astrophysics Data System (ADS)

Mader, Catherine; Doss, Heide; Plisch, Monica; Isola, Drew; Mirakovitz, Kathy

2011-04-01

We developed an education module on nuclear forensics, designed for high school science classrooms. The lessons include a mix of hands-on activities, computer simulations, and written exercises. Students are presented with realistic scenarios designed to develop their knowledge of nuclear science and its application to nuclear forensics. A two-day teacher workshop offered at Hope College attracted 20 teachers. They were loaned kits to implement activities with their students, and each teacher spent 3--7 days on the lessons. All who reported back said they would do it again and would share the lessons with colleagues. Many said that access to equipment and ready-made lessons enabled them to expand what they taught about nuclear science and introduce nuclear forensics. A few teachers invited guest speakers to their classroom, which provided an excellent opportunity to share career information with students. We acknowledge generous support from the Department of Homeland Security and the AIP Meggars Award.

Initiation of DNA replication requires actin dynamics and formin activity.

PubMed

Parisis, Nikolaos; Krasinska, Liliana; Harker, Bethany; Urbach, Serge; Rossignol, Michel; Camasses, Alain; Dewar, James; Morin, Nathalie; Fisher, Daniel

2017-11-02

Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms. © 2017 The Authors.

TNF-{alpha} promotes cell survival through stimulation of K{sup +} channel and NF{kappa}B activity in corneal epithelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Ling; Reinach, Peter; Lu, Luo

2005-11-15

Tumor necrosis factor (TNF-{alpha}) in various cell types induces either cell death or mitogenesis through different signaling pathways. In the present study, we determined in human corneal epithelial cells how TNF-{alpha} also promotes cell survival. Human corneal epithelial (HCE) cells were cultured in DMEM/F-12 medium containing 10% FBS. TNF-{alpha} stimulation induced activation of a voltage-gated K{sup +} channel detected by measuring single channel activity using patch clamp techniques. The effect of TNF-{alpha} on downstream events included NF{kappa}B nuclear translocation and increases in DNA binding activities, but did not elicit ERK, JNK, or p38 limb signaling activation. TNF-{alpha} induced increases inmore » p21 expression resulting in partial cell cycle attenuation in the G{sub 1} phase. Cell cycle progression was also mapped by flow cytometer analysis. Blockade of TNF-{alpha}-induced K{sup +} channel activity effectively prevented NF{kappa}B nuclear translocation and binding to DNA, diminishing the cell-survival protective effect of TNF-{alpha}. In conclusion, TNF-{alpha} promotes survival of HCE cells through sequential stimulation of K{sup +} channel and NF{kappa}B activities. This response to TNF-{alpha} is dependent on stimulating K{sup +} channel activity because following suppression of K{sup +} channel activity TNF-{alpha} failed to activate NF{kappa}B nuclear translocation and binding to nuclear DNA.« less

75 FR 44816 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-29

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0263] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: U.S. Nuclear Regulatory Commission (NRC). ACTION: Notice of pending NRC... individual monitoring for occupational radiation exposure during a monitoring (one calendar year) period to...

Using Nuclear Receptor Activity to Stratify Hepatocarcinogens

EPA Science Inventory

Nuclear receptors (NR) are a superfamily of ligand-activated transcription factors that control a range of cellular processes. Persistent stimulation of some NR is a non-genotoxic mechanism of rodent liver cancer with unclear relevance to humans. Here we report on a systematic an...

Active and Passive Diagnostic Signatures of Special Nuclear Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Myers, William L.; Karpius, Peter Joseph; Myers, Steven Charles

2017-05-26

An overview will be given discussing signatures associated with special nuclear materials acquired using both active and passive diagnostic techniques. Examples of how technology advancements have helped improve diagnostic capabilities to meet the challenges of today’s applications will be discussed.

A Boolean Network Model of Nuclear Receptor Mediated Cell Cycle Progression

EPA Science Inventory

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad range of cellular processes. Hormones, lipids and xenobiotics have been shown to activate NRs with a range of consequences on development, metabolism, oxidative stress, apoptosis, and prolif...

A Boolean Network Model of Nuclear Receptor Mediated Cell Cycle Progression (S)

EPA Science Inventory

Nuclear receptors (NRs) are ligand-activated transcription factors that regulate a broad range of cellular processes. Hormones, lipids and xenobiotics have been shown to activate NRs with a range of consequences on development, metabolism, oxidative stress, apoptosis, and prolif...

75 FR 17438 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2010-0141] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: U.S. Nuclear Regulatory Commission (NRC). ACTION: Notice of... new Agreement State applications. Annually for participation by Agreement States in the IMPEP reviews...

The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress

NASA Astrophysics Data System (ADS)

Mitić, M.; Simić, I.; Djordjević, J.; Radojčić, M. B.; Adžić, M.

2011-12-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.

Roles of the Nuclear Lamina in Stable Nuclear Association and Assembly of a Herpesviral Transactivator Complex on Viral Immediate-Early Genes

PubMed Central

Silva, Lindsey; Oh, Hyung Suk; Chang, Lynne; Yan, Zhipeng; Triezenberg, Steven J.; Knipe, David M.

2012-01-01

ABSTRACT Little is known about the mechanisms of gene targeting within the nucleus and its effect on gene expression, but most studies have concluded that genes located near the nuclear periphery are silenced by heterochromatin. In contrast, we found that early herpes simplex virus (HSV) genome complexes localize near the nuclear lamina and that this localization is associated with reduced heterochromatin on the viral genome and increased viral immediate-early (IE) gene transcription. In this study, we examined the mechanism of this effect and found that input virion transactivator protein, virion protein 16 (VP16), targets sites adjacent to the nuclear lamina and is required for targeting of the HSV genome to the nuclear lamina, exclusion of heterochromatin from viral replication compartments, and reduction of heterochromatin on the viral genome. Because cells infected with the VP16 mutant virus in1814 showed a phenotype similar to that of lamin A/C−/− cells infected with wild-type virus, we hypothesized that the nuclear lamina is required for VP16 activator complex formation. In lamin A/C−/− mouse embryo fibroblasts, VP16 and Oct-1 showed reduced association with the viral IE gene promoters, the levels of VP16 and HCF-1 stably associated with the nucleus were lower than in wild-type cells, and the association of VP16 with HCF-1 was also greatly reduced. These results show that the nuclear lamina is required for stable nuclear localization and formation of the VP16 activator complex and provide evidence for the nuclear lamina being the site of assembly of the VP16 activator complex. PMID:22251972

Nitrosative/oxidative stress conditions regulate thioredoxin-interacting protein (TXNIP) expression and thioredoxin-1 (TRX-1) nuclear localization.

PubMed

Ogata, Fernando Toshio; Batista, Wagner Luiz; Sartori, Adriano; Gesteira, Tarsis Ferreira; Masutani, Hiroshi; Arai, Roberto Jun; Yodoi, Junji; Stern, Arnold; Monteiro, Hugo Pequeno

2013-01-01

Thioredoxin (TRX-1) is a multifunctional protein that controls the redox status of other proteins. TRX-1 can be found in the extracellular milieu, cytoplasm and nucleus, and it has distinct functions in each environment. Previously, we studied the intracellular localization of TRX-1 and its relationship with the activation of the p21Ras-ERK1/2 MAP Kinases signaling pathway. In situations where this pathway was activated by stress conditions evoked by a nitrosothiol, S-nitroso-N-acetylpenicillamine (SNAP), TRX-1 accumulated in the nuclear compartment due to nitrosylation of p21Ras and activation of downstream ERK1/2 MAP kinases. Presently, we demonstrate that ERK1/2 MAP Kinases activation and spatial distribution within cells trigger TRX-1 nuclear translocation through down-regulation of the physiological inhibitor of TRX-1, Thioredoxin Interacting Protein (TXNIP). Once activated by the oxidants, SNAP and H₂O₂, the ERK1/2 MAP kinases migrate to the nucleus. This is correlated with down-regulation of TXNIP. In the presence of the MEK inhibitors (PD98059 or UO126), or in cells transfected with the Protein Enriched in Astrocytes (PEA-15), a cytoplasmic anchor of ERK1/2 MAP kinases, TRX-1 nuclear migration and TXNIP down-regulation are no longer observed in cells exposed to oxidants. On the other hand, over-expression of TXNIP abolishes nuclear migration of TRX-1 under nitrosative/oxidative stress conditions, whereas gene silencing of TXNIP facilitates nuclear migration even in the absence of stress conditions. Studies based on the TXNIP promoter support this regulation. In conclusion, changes in TRX-1 compartmentalization under nitrosative/oxidative stress conditions are dependent on the expression levels of TXNIP, which are regulated by cellular compartmentalization and activation of the ERK1/2 MAP kinases.

Iron-Inducible Nuclear Translocation of a Myb3 Transcription Factor in the Protozoan Parasite Trichomonas vaginalis

PubMed Central

Hsu, Hong-Ming; Lee, Yu; Indra, Dharmu; Wei, Shu-Yi; Liu, Hsing-Wei; Chang, Lung-Chun; Chen, Chinpan; Ong, Shiou-Jeng

2012-01-01

In Trichomonas vaginalis, a novel nuclear localization signal spanning the folded R2R3 DNA-binding domain of a Myb2 protein was previously identified. To study whether a similar signal is used for nuclear translocation by other Myb proteins, nuclear translocation of Myb3 was examined in this report. When overexpressed, hemagglutinin-tagged Myb3 was localized to nuclei of transfected cells, with a cellular distribution similar to that of endogenous Myb3. Fusion to a bacterial tetracycline repressor, R2R3, of Myb3 that spans amino acids (aa) 48 to 156 was insufficient for nuclear translocation of the fusion protein, unless its C terminus was extended to aa 167. The conserved isoleucine in helix 2 of R2R3, which is important for Myb2's structural integrity in maintaining DNA-binding activity and nuclear translocation, was also vital for the former activity of Myb3, but less crucial for the latter. Sequential nuclear influx and efflux of Myb3, which require further extension of the nuclear localization signal to aa 180, were immediately induced after iron repletion. Sequence elements that regulate nuclear translocation with cytoplasmic retention, nuclear influx, and nuclear efflux were identified within the C-terminal tail. These results suggest that the R2R3 DNA-binding domain also serves as a common module for the nuclear translocation of both Myb2 and Myb3, but there are intrinsic differences between the two nuclear localization signals. PMID:23042127

Novel mode of phosphorylation-triggered reorganization of the nuclear lamina during nuclear egress of human cytomegalovirus.

PubMed

Milbradt, Jens; Webel, Rike; Auerochs, Sabrina; Sticht, Heinrich; Marschall, Manfred

2010-04-30

The nucleocytoplasmic egress of viral capsids is a rate-limiting step in the replication of the human cytomegalovirus (HCMV). As reported recently, an HCMV-specific nuclear egress complex is composed of viral and cellular proteins, in particular protein kinases with the capacity to induce destabilization of the nuclear lamina. Viral protein kinase pUL97 and cellular protein kinase C (PKC) play important roles by phosphorylating several types of nuclear lamins. Using pUL97 mutants, we show that the lamin-phosphorylating activity of pUL97 is associated with a reorganization of nuclear lamin A/C. Either pUL97 or PKC has the potential to induce distinct punctate lamina-depleted areas at the periphery of the nuclear envelope, which were detectable in transiently transfected and HCMV-infected cells. Using recombinant HCMV, which produces green fluorescent protein-labeled viral capsids, the direct transition of viral capsids through these areas could be visualized. This process was sensitive to an inhibitor of pUL97/PKC activity. The pUL97-mediated phosphorylation of lamin A/C at Ser(22) generated a novel binding motif for the peptidyl-prolyl cis/trans-isomerase Pin1. In HCMV-infected fibroblasts, the physiological localization of Pin1 was altered, leading to recruitment of Pin1 to viral replication centers and to the nuclear lamina. The local increase in Pin1 peptidyl-prolyl cis/trans-isomerase activity may promote conformational modulation of lamins. Thus, we postulate a novel phosphorylation-triggered mechanism for the reorganization of the nuclear lamina in HCMV-infected cells.

Novel Mode of Phosphorylation-triggered Reorganization of the Nuclear Lamina during Nuclear Egress of Human Cytomegalovirus*

PubMed Central

Milbradt, Jens; Webel, Rike; Auerochs, Sabrina; Sticht, Heinrich; Marschall, Manfred

2010-01-01

The nucleocytoplasmic egress of viral capsids is a rate-limiting step in the replication of the human cytomegalovirus (HCMV). As reported recently, an HCMV-specific nuclear egress complex is composed of viral and cellular proteins, in particular protein kinases with the capacity to induce destabilization of the nuclear lamina. Viral protein kinase pUL97 and cellular protein kinase C (PKC) play important roles by phosphorylating several types of nuclear lamins. Using pUL97 mutants, we show that the lamin-phosphorylating activity of pUL97 is associated with a reorganization of nuclear lamin A/C. Either pUL97 or PKC has the potential to induce distinct punctate lamina-depleted areas at the periphery of the nuclear envelope, which were detectable in transiently transfected and HCMV-infected cells. Using recombinant HCMV, which produces green fluorescent protein-labeled viral capsids, the direct transition of viral capsids through these areas could be visualized. This process was sensitive to an inhibitor of pUL97/PKC activity. The pUL97-mediated phosphorylation of lamin A/C at Ser22 generated a novel binding motif for the peptidyl-prolyl cis/trans-isomerase Pin1. In HCMV-infected fibroblasts, the physiological localization of Pin1 was altered, leading to recruitment of Pin1 to viral replication centers and to the nuclear lamina. The local increase in Pin1 peptidyl-prolyl cis/trans-isomerase activity may promote conformational modulation of lamins. Thus, we postulate a novel phosphorylation-triggered mechanism for the reorganization of the nuclear lamina in HCMV-infected cells. PMID:20202933

JPRS Report, Nuclear Developments

DTIC Science & Technology

1988-06-03

arranged according to degree of severity, and action plans will be developed for necessary measures appropriate to each level. Nuclear Disaster Chief...For the purpose of shielding the country as much as possible from the damages of nuclear accidents, first, a " Nuclear Disaster Headquarters" will be...formed within TAEC to oversee operations called for by the " Nuclear Disaster Guidelines," and coordination of the activities designed to meet an

Phospholipid Regulation of the Nuclear Receptor Superfamily

PubMed Central

Crowder, Mark K.; Seacrist, Corey D.; Blind, Raymond D.

2016-01-01

Nuclear receptors are ligand-activated transcription factors whose diverse biological functions are classically regulated by cholesterol-based small molecules. Over the past few decades, a growing body of evidence has demonstrated that phospholipids and other similar amphipathic molecules can also specifically bind and functionally regulate the activity of certain nuclear receptors, suggesting a critical role for these non-cholesterol-based molecules in transcriptional regulation. Phosphatidylcholines, phosphoinositides and sphingolipids are a few of the many phospholipid like molecules shown to quite specifically regulate nuclear receptors in mouse models, cell lines and in vitro. More recent evidence has also shown that certain nuclear receptors can “present” a bound phospholipid headgroup to key lipid signaling enzymes, which can then modify the phospholipid headgroup with very unique kinetic properties. Here, we review the broad array of phospholipid / nuclear receptor interactions, from the perspective of the chemical nature of the phospholipid, and the cellular abundance of the phospholipid. We also view the data in the light of well established paradigms for phospholipid mediated transcriptional regulation, as well as newer models of how phospholipids might effect transcription in the acute regulation of complex nuclear signaling pathways. Thus, this review provides novel insight into the new, non-membrane associated roles nuclear phospholipids play in regulating complex nuclear events, centered on the nuclear receptor superfamily of transcription factors. PMID:27838257

Nuclear starburst activity induced by elongated bulges in spiral galaxies

NASA Astrophysics Data System (ADS)

Kim, Eunbin; Kim, Sungsoo S.; Choi, Yun-Young; Lee, Gwang-Ho; de Grijs, Richard; Lee, Myung Gyoon; Hwang, Ho Seong

2018-06-01

We study the effects of bulge elongation on the star formation activity in the centres of spiral galaxies using the data from the Sloan Digital Sky Survey Data Release 7. We construct a volume-limited sample of face-on spiral galaxies with Mr < -19.5 mag at 0.02 ≤z< 0.055 by excluding barred galaxies, where the aperture of the SDSS spectroscopic fibre covers the bulges of the galaxies. We adopt the ellipticity of bulges measured by Simard et al. (2011) who performed two-dimensional bulge+disc decompositions using the SDSS images of galaxies, and identify nuclear starbursts using the fibre specific star formation rates derived from the SDSS spectra. We find a statistically significant correlation between bulge elongation and nuclear starbursts in the sense that the fraction of nuclear starbursts increases with bulge elongation. This correlation is more prominent for fainter and redder galaxies, which exhibit higher ratios of elongated bulges. We find no significant environmental dependence of the correlation between bulge elongation and nuclear starbursts. These results suggest that non-axisymmetric bulges can efficiently feed the gas into the centre of galaxies to trigger nuclear starburst activity.

MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Teng, E-mail: tengyu33@yahoo.com; Ji, Jiang; Guo, Yong-li

2013-11-08

Highlights: •Curcumin activates MST1 in melanoma cells. •MST1 mediates curcumin-induced apoptosis of melanoma cells. •ROS production is involved in curcumin-induced MST1 activation. •MST1 mediates curcumin-induced JNK activation in melanoma cells. •MST1 mediates curcumin-induced Foxo3a nuclear translocation and Bim expression. -- Abstract: Different groups including ours have shown that curcumin induces melanoma cell apoptosis, here we focused the role of mammalian Sterile 20-like kinase 1 (MST1) in it. We observed that curcumin activated MST1-dependent apoptosis in cultured melanoma cells. MST1 silencing by RNA interference (RNAi) suppressed curcumin-induced cell apoptosis, while MST1 over-expressing increased curcumin sensitivity. Meanwhile, curcumin induced reactive oxygen speciesmore » (ROS) production in melanoma cells, and the ROS scavenger, N-acetyl-cysteine (NAC), almost blocked MST1 activation to suggest that ROS might be required for MST1 activation by curcumin. c-Jun N-terminal protein kinase (JNK) activation by curcumin was dependent on MST1, since MST1 inhibition by RNAi or NAC largely inhibited curcumin-induced JNK activation. Further, curcumin induced Foxo3 nuclear translocation and Bim-1 (Foxo3 target gene) expression in melanoma cells, such an effect by curcumin was inhibited by MST1 RNAi. In conclusion, we suggested that MST1 activation by curcumin mediates JNK activation, Foxo3a nuclear translocation and apoptosis in melanoma cells.« less

Retinoic Acid Inducible Gene 1 Protein (RIG1)-like Receptor Pathway is Required for Efficient Nuclear Reprogramming

PubMed Central

Sayed, Nazish; Ospino, Frank; Himmati, Farhan; Lee, Jieun; Chanda, Palas; Mocarski, Edward S.; Cooke, John P.

2017-01-01

We have revealed a critical role for innate immune signaling in nuclear reprogramming to pluripotency, and in the nuclear reprogramming required for somatic cell transdifferentiation. Activation of innate immune signaling causes global changes in the expression and activity of epigenetic modifiers to promote epigenetic plasticity. In our previous papers, we focused on the role of toll-like receptor 3 (TLR3) in this signaling pathway. Here we define the role of another innate immunity pathway known to participate in the response to viral RNA, the retinoic acid-inducible gene 1 receptor (RIG-1)-like receptor (RLR) pathway. This pathway is represented by the sensors of viral RNA, RIG-1, LGP2 and MDA5. We first found that TLR3 deficiency only causes a partial inhibition of nuclear reprogramming to pluripotency in mouse tail-tip fibroblasts, which motivated us to determine the contribution of RLR. We found that knockdown of iPS-1, the common adaptor protein for the RLR family, substantially reduced nuclear reprogramming induced by retroviral or by mmRNA expression of Oct 4, Sox2, KLF4 and cMYC (OSKM). Importantly a double knockdown of both RLR and TLR3 pathway led to a further decrease in iPSC colonies suggesting an additive effect of both these pathways on nuclear reprogramming. Furthermore, in murine embryonic fibroblasts expressing a dox-inducible cassette of the genes encoding OSKM, an RLR agonist increased the yield of iPSCs. Similarly, the RLR agonist enhanced nuclear reprogramming by cell permeant peptides of the Yamanaka factors. Finally, in the dox-inducible system, RLR activation promotes activating histone marks in the promoter region of pluripotency genes. To conclude, innate immune signaling mediated by RLR plays a critical role in nuclear reprogramming. Manipulation of innate immune signaling may facilitate nuclear reprogramming to achieve pluripotency. PMID:28276156

Historically Black Colleges and Universities Nuclear Energy Training Program: Summary of program activities, fiscal year 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1987-04-27

The Historically Black Colleges and Universities Nuclear Energy Training (HBCU NET) Program, funded by DOE, Office of Nuclear Energy and administered by ORAU, began in February 1984. The program provides support for training, study, research participation, and academic enrichment of students and faculty at designated HBCUs in nuclear science, nuclear engineering, and other nuclear-related technologes and disciplines. The program is composed of undergraduate scholarships, graduate fellowships, student and faculty research participation, and an annual student training institute.

EXAMINING THE ROLE AND RESEARCH CHALLENGES OF SOCIAL MEDIA AS A TOOL FOR NONPROLIFERATION AND ARMS CONTROL TREATY VERIFICATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, Michael J.; Cramer, Nicholas O.; Benz, Jacob M.

Traditional arms control treaty verification activities typically involve a combination of technical measurements via physical and chemical sensors, state declarations, political agreements, and on-site inspections involving international subject matter experts. However, the ubiquity of the internet, and the electronic sharing of data that it enables, has made available a wealth of open source information with the potential to benefit verification efforts. Open source information is already being used by organizations such as the International Atomic Energy Agency to support the verification of state-declared information, prepare inspectors for in-field activities, and to maintain situational awareness . The recent explosion in socialmore » media use has opened new doors to exploring the attitudes, moods, and activities around a given topic. Social media platforms, such as Twitter, Facebook, and YouTube, offer an opportunity for individuals, as well as institutions, to participate in a global conversation at minimal cost. Social media data can also provide a more data-rich environment, with text data being augmented with images, videos, and location data. The research described in this paper investigates the utility of applying social media signatures as potential arms control and nonproliferation treaty verification tools and technologies, as determined through a series of case studies. The treaty relevant events that these case studies touch upon include detection of undeclared facilities or activities, determination of unknown events recorded by the International Monitoring System (IMS), and the global media response to the occurrence of an Indian missile launch. The case studies examine how social media can be used to fill an information gap and provide additional confidence to a verification activity. The case studies represent, either directly or through a proxy, instances where social media information may be available that could potentially augment the evaluation of an event. The goal of this paper is to instigate a discussion within the verification community as to where and how social media can be effectively utilized to complement and enhance traditional treaty verification efforts. In addition, this paper seeks to identify areas of future research and development necessary to adapt social media analytic tools and techniques, and to form the seed for social media analytics to aid and inform arms control and nonproliferation policymakers and analysts. While social media analysis (as well as open source analysis as a whole) will not ever be able to replace traditional arms control verification measures, they do supply unique signatures that can augment existing analysis.« less

10 CFR 770.1 - What is the purpose of this part?

Code of Federal Regulations, 2013 CFR

2013-01-01

... Energy DEPARTMENT OF ENERGY TRANSFER OF REAL PROPERTY AT DEFENSE NUCLEAR FACILITIES FOR ECONOMIC... or lease real property at defense nuclear facilities for economic development. (b) This part also... DOE activities at the defense nuclear facility. ...

Genetics Home Reference: anhidrotic ectodermal dysplasia with immune deficiency

MedlinePlus

... The proteins produced from these two genes regulate nuclear factor-kappa-B. Nuclear factor-kappa-B is a group of related ... proteins with impaired function, which reduces activation of nuclear factor-kappa-B. These changes disrupt certain signaling ...

Host and viral determinants for MxB restriction of HIV-1 infection.

PubMed

Matreyek, Kenneth A; Wang, Weifeng; Serrao, Erik; Singh, Parmit Kumar; Levin, Henry L; Engelman, Alan

2014-10-25

Interferon-induced cellular proteins play important roles in the host response against viral infection. The Mx family of dynamin-like GTPases, which include MxA and MxB, target a wide variety of viruses. Despite considerable evidence demonstrating the breadth of antiviral activity of MxA, human MxB was only recently discovered to specifically inhibit lentiviruses. Here we assess both host and viral determinants that underlie MxB restriction of HIV-1 infection. Heterologous expression of MxB in human osteosarcoma cells potently inhibited HIV-1 infection (~12-fold), yet had little to no effect on divergent retroviruses. The anti-HIV effect manifested as a partial block in the formation of 2-long terminal repeat circle DNA and hence nuclear import, and we accordingly found evidence for an additional post-nuclear entry block. A large number of previously characterized capsid mutations, as well as mutations that abrogated integrase activity, counteracted MxB restriction. MxB expression suppressed integration into gene-enriched regions of chromosomes, similar to affects observed previously when cells were depleted for nuclear transport factors such as transportin 3. MxB activity did not require predicted GTPase active site residues or a series of unstructured loops within the stalk domain that confer functional oligomerization to related dynamin family proteins. In contrast, we observed an N-terminal stretch of residues in MxB to harbor key determinants. Protein localization conferred by a nuclear localization signal (NLS) within the N-terminal 25 residues, which was critical, was fully rescuable by a heterologous NLS. Consistent with this observation, a heterologous nuclear export sequence (NES) abolished full-length MxB activity. We additionally mapped sub-regions within amino acids 26-90 that contribute to MxB activity, finding sequences present within residues 27-50 particularly important. MxB inhibits HIV-1 by interfering with minimally two steps of infection, nuclear entry and post-nuclear trafficking and/or integration, without destabilizing the inherent catalytic activity of viral preintegration complexes. Putative MxB GTPase active site residues and stalk domain Loop 4 -- both previously shown to be necessary for MxA function -- were dispensable for MxB antiviral activity. Instead, we highlight subcellular localization and a yet-determined function(s) present in the unique MxB N-terminal region to be required for HIV-1 restriction.

Review of CBRN Medical and Operational Terminologies in NATO CBRN Publications

DTIC Science & Technology

2016-08-01

repository for NATO terminology and is used to search terms, abbreviations, and definitions found in NATO documents, communications, and activities of all...21 is a compilation of terminology used in NATO chemical, biological, radiological, and nuclear defense activities , documentation, and communications...informational constructs, activities , and functionality necessary for: 1. Reporting of all chemical, biological or radiological incidents and nuclear

The Air Force Nuclear Engineering Center Structural Activation and Integrity Evaluation

DTIC Science & Technology

1990-03-01

Vi1 List of Figures Figure Page 1. Inside Piqua Nuclear Power Facility containment building on top of the entombed reactor core ... 5...5. Predicted activity percentage of individual materials in the AFNEC ..... ........................ 21 6. Predicted radioisotope activity percentage...of total radioisotopic inventory within entombment at 20 years after shutdown ......................... 23 iv List of Tables Table Page 1. ORIGEN2

76 FR 52698 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-23

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2011-0181] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: Nuclear Regulatory Commission (NRC). ACTION: Notice of pending... administration of the byproduct material or the radiation there from to human beings or animals. Possession of...

75 FR 39054 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-07

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0234] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: U.S. Nuclear Regulatory Commission (NRC). ACTION: Notice of pending NRC..., or wishing to participate in a license application review for the potential geologic repository. 5...

75 FR 45676 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2010-0235] Agency Information Collection Activities: Proposed Collection; Comment Request AGENCY: U.S. Nuclear Regulatory Commission (NRC). ACTION: Notice of...: Applications for new licenses and amendments may be submitted at any time. Applications for renewal are...

75 FR 37841 - Agency Information Collection Activities: Proposed Collection; Comment Request

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DOE Office of Scientific and Technical Information (OSTI.GOV)

Vins, M.

This contribution overviews neutron spectrum measurement, which was done on training reactor VR-1 Sparrow with a new nuclear fuel. Former nuclear fuel IRT-3M was changed for current nuclear fuel IRT-4M with lower enrichment of 235U (enrichment was reduced from former 36% to 20%) in terms of Reduced Enrichment for Research and Test Reactors (RERTR) Program. Neutron spectrum measurement was obtained by irradiation of activation foils at the end of pipe of rabit system and consecutive deconvolution of obtained saturated activities. Deconvolution was performed by computer iterative code SAND-II with 620 groups' structure. All gamma measurements were performed on Canberra HPGe.more » Activation foils were chosen according physical and nuclear parameters from the set of certificated foils. The Resulting differential flux at the end of pipe of rabit system agreed well with typical spectrum of light water reactor. Measurement of neutron spectrum has brought better knowledge about new reactor core C1 and improved methodology of activation measurement. (author)« less

Isotopic signature of atmospheric xenon released from light water reactors.

PubMed

Kalinowski, Martin B; Pistner, Christoph

2006-01-01

A global monitoring system for atmospheric xenon radioactivity is being established as part of the International Monitoring System to verify compliance with the Comprehensive Nuclear-Test-Ban Treaty (CTBT). The isotopic activity ratios of (135)Xe, (133m)Xe, (133)Xe and (131m)Xe are of interest for distinguishing nuclear explosion sources from civilian releases. Simulations of light water reactor (LWR) fuel burn-up through three operational reactor power cycles are conducted to explore the possible xenon isotopic signature of nuclear reactor releases under different operational conditions. It is studied how ratio changes are related to various parameters including the neutron flux, uranium enrichment and fuel burn-up. Further, the impact of diffusion and mixing on the isotopic activity ratio variability are explored. The simulations are validated with reported reactor emissions. In addition, activity ratios are calculated for xenon isotopes released from nuclear explosions and these are compared to the reactor ratios in order to determine whether the discrimination of explosion releases from reactor effluents is possible based on isotopic activity ratios.

A Novel Nuclear Trafficking Module Regulates the Nucleocytoplasmic Localization of the Rabies Virus Interferon Antagonist, P Protein*

PubMed Central

Oksayan, Sibil; Wiltzer, Linda; Rowe, Caitlin L.; Blondel, Danielle; Jans, David A.; Moseley, Gregory W.

2012-01-01

Regulated nucleocytoplasmic transport of proteins is central to cellular function and dysfunction during processes such as viral infection. Active protein trafficking into and out of the nucleus is dependent on the presence within cargo proteins of intrinsic specific modular signals for nuclear import (nuclear localization signals, NLSs) and export (nuclear export signals, NESs). Rabies virus (RabV) phospho (P) protein, which is largely responsible for antagonising the host anti-viral response, is expressed as five isoforms (P1–P5). The subcellular trafficking of these isoforms is thought to depend on a balance between the activities of a dominant N-terminal NES (N-NES) and a distinct C-terminal NLS (C-NLS). Specifically, the N-NES-containing isoforms P1 and P2 are cytoplasmic, whereas the shorter P3–P5 isoforms, which lack the N-NES, are believed to be nuclear through the activity of the C-NLS. Here, we show for the first time that RabV P contains an additional strong NLS in the N-terminal region (N-NLS), which, intriguingly, overlaps with the N-NES. This arrangement represents a novel nuclear trafficking module where the N-NLS is inactive in P1 but becomes activated in P3, concomitant with truncation of the N-NES, to become the principal targeting signal conferring nuclear accumulation. Understanding this unique switch arrangement of overlapping, co-regulated NES/NLS sequences is vital to delineating the critical role of RabV P protein in viral infection. PMID:22700958

Irregular migration and informal economy in Southern and Central-Eastern Europe: breaking the vicious cycle?

PubMed

Maroukis, Thanos; Iglicka, Krystyna; Gmaj, Katarzyna

2011-01-01

The flexible and cheap labour that European “post-industrial” economies are in need of is often facilitated by undeclared labour. The undocumented migrant, from his/her part, relatively easily finds work that suits his -- at least initial -- plans. What lies behind this nexus between irregular migration and informal economy? To what extent can this nexus be attributed to the structural features of the so-called “secondary”, as opposed to “primary”, labour market? And how does migration policy correlate with this economic context and lead to the entrapment of migrants in irregularity? Finally, can this vicious cycle of interests and life-strategies be broken and what does the experience of the migrants indicate in this respect? This paper addresses these questions via an exploration of the grounds upon which irregular migration and the shadow economy complement each other in southern Europe (SE) and central and Eastern Europe (CEE) (two regions at different points in the migration cycle). In doing so, the dynamic character of the nexus between informal economy and irregular migration will come to the fore, and the abstract identity of the “average” undocumented migrant will be deconstructed.

Cocaine adulteration.

PubMed

Kudlacek, Oliver; Hofmaier, Tina; Luf, Anton; Mayer, Felix P; Stockner, Thomas; Nagy, Constanze; Holy, Marion; Freissmuth, Michael; Schmid, Rainer; Sitte, Harald H

2017-10-01

Cocaine is a naturally occurring and illicitly used psychostimulant drug. Cocaine acts at monoaminergic neurotransmitter transporters to block uptake of the monoamines, dopamine, serotonin and norepinephrine. The resulting increase of monoamines in the extracellular space underlies the positively reinforcing effects that cocaine users seek. In turn, this increase in monoamines underlies the development of addiction, and can also result in a number of severe side effects. Currently, cocaine is one of the most common illicit drugs available on the European market. However, cocaine is increasingly sold in impure forms. This trend is driven by cocaine dealers seeking to increase their profit margin by mixing ("cutting") cocaine with numerous other compounds ("adulterants"). Importantly, these undeclared compounds put cocaine consumers at risk, because consumers are not aware of the additional potential threats to their health. This review describes adulterants that have been identified in cocaine sold on the street market. Their typical pharmacological profile and possible reasons why these compounds can be used as cutting agents will be discussed. Since a subset of these adulterants has been found to exert effects similar to cocaine itself, we will discuss levamisole, the most frequently used cocaine cutting agent today, and its metabolite aminorex. Copyright © 2017. Published by Elsevier B.V.

Advanced DNA- and Protein-based Methods for the Detection and Investigation of Food Allergens.

PubMed

Prado, M; Ortea, I; Vial, S; Rivas, J; Calo-Mata, P; Barros-Velázquez, J

2016-11-17

Currently, food allergies are an important health concern worldwide. The presence of undeclared allergenic ingredients or the presence of traces of allergens due to contamination during food processing poses a great health risk to sensitized individuals. Therefore, reliable analytical methods are required to detect and identify allergenic ingredients in food products. The present review addresses the recent developments regarding the application of DNA- and protein-based methods for the detection of allergenic ingredients in foods. The fitness-for-purpose of reviewed methodology will be discussed, and future trends will be highlighted. Special attention will be given to the evaluation of the potential of newly developed and promising technologies that can improve the detection and identification of allergenic ingredients in foods, such as the use of biosensors and/or nanomaterials to improve detection limits, specificity, ease of use, or to reduce the time of analysis. Such rapid food allergen test methods are required to facilitate the reliable detection of allergenic ingredients by control laboratories, to give the food industry the means to easily determine whether its product has been subjected to cross-contamination and, simultaneously, to identify how and when this cross-contamination occurred.

Using a portable ion mobility spectrometer to screen dietary supplements for sibutramine.

PubMed

Dunn, Jamie D; Gryniewicz-Ruzicka, Connie M; Kauffman, John F; Westenberger, Benjamin J; Buhse, Lucinda F

2011-02-20

In response to recent incidents of undeclared sibutramine, an appetite suppressant found in dietary supplements, we developed a method to detect sibutramine using hand-held ion mobility spectrometers with an analysis time of 15 s. Ion mobility spectrometry is a high-throughput and sensitive technique that has been used for illicit drug, explosive, volatile organic compound and chemical warfare detection. We evaluated a hand-held ion mobility spectrometer as a tool for the analysis of supplement extracts containing sibutramine. The overall instrumental limit of detection of five portable ion mobility spectrometers was 2 ng of sibutramine HCl. When sample extractions containing 30 ng/μl or greater of sibutramine were analyzed, saturation of the ionization chamber of the spectrometer occurred and the instrument required more than three cleaning cycles to remove the drug. Hence, supplement samples suspected of containing sibutramine should be prepared at concentrations of 2-20 ng/μl. To obtain this target concentration range for products containing unknown amounts of sibutramine, we provided a simple sample preparation procedure, allowing the U.S. Food and Drug Administration or other agencies to screen products using the portable ion mobility spectrometer. Published by Elsevier B.V.

DNA damage-induced nuclear translocation of Apaf-1 is mediated by nucleoporin Nup107

PubMed Central

Jagot-Lacoussiere, Léonard; Faye, Audrey; Bruzzoni-Giovanelli, Heriberto; Villoutreix, Bruno O; Rain, Jean-Christophe; Poyet, Jean-Luc

2015-01-01

Beside its central role in the mitochondria-dependent cell death pathway, the apoptotic protease activating factor 1 (Apaf-1) is involved in the DNA damage response through cell-cycle arrest induced by genotoxic stress. This non-apoptotic function requires a nuclear translocation of Apaf-1 during the G1-to-S transition. However, the mechanisms that trigger the nuclear accumulation of Apaf-1 upon DNA damage remain to be investigated. Here we show that the main 4 isoforms of Apaf-1 can undergo nuclear translocation and restore Apaf-1 deficient MEFs cell cycle arrest in the S phase following genotoxic stress through activation of Chk-1. Interestingly, DNA damage-dependent nuclear accumulation of Apaf-1 occurs independently of p53 and the retinoblastoma (pRb) pathway. We demonstrated that Apaf-1 associates with the nucleoporin Nup107 and this association is necessary for Apaf-1 nuclear import. The CED-4 domain of Apaf-1 directly binds to the central domain of Nup107 in an ATR-regulated, phosphorylation-dependent manner. Interestingly, expression of the Apaf-1-interacting domain of Nup107 interfered with Apaf-1 nuclear translocation upon genotoxic stress, resulting in a marked reduction of Chk-1 activation and cell cycle arrest. Thus, our results confirm the crucial role of Apaf-1 nuclear relocalization in mediating cell-cycle arrest induced by genotoxic stress and implicate Nup107 as a critical regulator of the DNA damage-induced intra-S phase checkpoint response. PMID:25695197

Methamphetamine toxicity-induced calcineurin activation, nuclear translocation of nuclear factor of activated T-cells and elevation of cyclooxygenase 2 levels are averted by calpastatin overexpression in neuroblastoma SH-SY5Y cells.

PubMed

Chetsawang, Jirapa; Nudmamud-Thanoi, Sutisa; Phonchai, Ruchee; Abubakar, Zuroida; Govitrapong, Piyarat; Chetsawang, Banthit

2018-06-23

Methamphetamine (METH) is an addictive stimulant drug that has many negative consequences, including toxic effects to the brain. Recently, the induction of inflammatory processes has been identified as a potential contributing factor to induce neuronal cell degeneration. It has been demonstrated that the expression of inflammatory agents, such as cyclooxygenase 2 (COX-2), depends on the activation of calcineurin (CaN) and nuclear factor of activated T-cells (NFAT). Moreover, the excessive elevation in cytosolic Ca 2+ levels activates the cell death process, including calpain activation in neurons, which was diminished by the overexpression of the calpain inhibitor protein, calpastatin. However, it is unclear whether calpain mediates CaN-NFAT activation in the neurotoxic process. In the present study, we observed that the toxic high dose of METH-treated neuroblastoma SH-SY5Y cells significantly decreased cell viability but increased apoptotic cell death, the active cleaved form of calcineurin, the nuclear translocation of NFAT, and COX-2 levels. Nevertheless, these toxic effects were diminished in METH-treated calpastatin-overexpressing SH-SY5Y cells. These findings might emphasize the role of calpastatin against METH-induced toxicity by a mechanism related to calpain-dependent CaN-NFAT activation-induced COX-2 expression. Copyright © 2018. Published by Elsevier B.V.

Ferulic acid (FA) abrogates γ-radiation induced oxidative stress and DNA damage by up-regulating nuclear translocation of Nrf2 and activation of NHEJ pathway.

PubMed

Das, Ujjal; Manna, Krishnendu; Khan, Amitava; Sinha, Mahuya; Biswas, Sushobhan; Sengupta, Aaveri; Chakraborty, Anindita; Dey, Sanjit

2017-01-01

The present study was aimed to evaluate the radioprotective effect of ferulic acid (FA), a naturally occurring plant flavonoid in terms of DNA damage and damage related alterations of repair pathways by gamma radiation. FA was administered at a dose of 50 mg/kg body weight for five consecutive days prior to exposing the swiss albino mice to a single dose of 10 Gy gamma radiation. Ionising radiation induces oxidative damage manifested by decreased expression of Cu, Zn-SOD (SOD stands for super oxide dismutase), Mn-SOD and catalase. Gamma radiation promulgated reactive oxygen species (ROS) mediated DNA damage and modified repair pathways. ROS enhanced nuclear translocation of p53, activated ATM (ataxia telangiectasia-mutated protein), increased expression of GADD45a (growth arrest and DNA-damage-inducible protein) gene and inactivated Non homologous end joining (NHEJ) repair pathway. The comet formation in irradiated mice peripheral blood mononuclear cells (PBMC) reiterated the DNA damage in IR exposed groups. FA pretreatment significantly prevented the comet formation and regulated the nuclear translocation of p53, inhibited ATM activation and expression of GADD45a gene. FA promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and activated NHEJ repair pathway to overcome ROS mediated oxidative stress and DNA damage. Therefore, the current study stated that FA can challenge the oxidative stress by (i) inducing nuclear translocation of Nrf2, (ii) scavenging ROS, and (iii) activating NHEJ DNA repair process.

77 FR 75452 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

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2011-11-21

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NSR&D Program Fiscal Year (FY) 2015 Call for Proposals Mitigation of Seismic Risk at Nuclear Facilities using Seismic Isolation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Coleman, Justin

2015-02-01

Seismic isolation (SI) has the potential to drastically reduce seismic response of structures, systems, or components (SSCs) and therefore the risk associated with large seismic events (large seismic event could be defined as the design basis earthquake (DBE) and/or the beyond design basis earthquake (BDBE) depending on the site location). This would correspond to a potential increase in nuclear safety by minimizing the structural response and thus minimizing the risk of material release during large seismic events that have uncertainty associated with their magnitude and frequency. The national consensus standard America Society of Civil Engineers (ASCE) Standard 4, Seismic Analysismore » of Safety Related Nuclear Structures recently incorporated language and commentary for seismically isolating a large light water reactor or similar large nuclear structure. Some potential benefits of SI are: 1) substantially decoupling the SSC from the earthquake hazard thus decreasing risk of material release during large earthquakes, 2) cost savings for the facility and/or equipment, and 3) applicability to both nuclear (current and next generation) and high hazard non-nuclear facilities. Issue: To date no one has evaluated how the benefit of seismic risk reduction reduces cost to construct a nuclear facility. Objective: Use seismic probabilistic risk assessment (SPRA) to evaluate the reduction in seismic risk and estimate potential cost savings of seismic isolation of a generic nuclear facility. This project would leverage ongoing Idaho National Laboratory (INL) activities that are developing advanced (SPRA) methods using Nonlinear Soil-Structure Interaction (NLSSI) analysis. Technical Approach: The proposed study is intended to obtain an estimate on the reduction in seismic risk and construction cost that might be achieved by seismically isolating a nuclear facility. The nuclear facility is a representative pressurized water reactor building nuclear power plant (NPP) structure. Figure 1: Project activities The study will consider a representative NPP reinforced concrete reactor building and representative plant safety system. This study will leverage existing research and development (R&D) activities at INL. Figure 1 shows the proposed study steps with the steps in blue representing activities already funded at INL and the steps in purple the activities that would be funded under this proposal. The following results will be documented: 1) Comparison of seismic risk for the non-seismically isolated (non-SI) and seismically isolated (SI) NPP, and 2) an estimate of construction cost savings when implementing SI at the site of the generic NPP.« less

Fission Activities of the Nuclear Reactions Group in Uppsala

NASA Astrophysics Data System (ADS)

Al-Adili, A.; Alhassan, E.; Gustavsson, C.; Helgesson, P.; Jansson, K.; Koning, A.; Lantz, M.; Mattera, A.; Prokofiev, A. V.; Rakopoulos, V.; Sjöstrand, H.; Solders, A.; Tarrío, D.; Österlund, M.; Pomp, S.

This paper highlights some of the main activities related to fission of the nuclear reactions group at Uppsala University. The group is involved for instance in fission yield experiments at the IGISOL facility, cross-section measurements at the NFS facility, as well as fission dynamics studies at the IRMM JRC-EC. Moreover, work is ongoing on the Total Monte Carlo (TMC) methodology and on including the GEF fission code into the TALYS nuclear reaction code. Selected results from these projects are discussed.

Thin layer activation techniques at the U-120 cyclotron of Bucharest

NASA Astrophysics Data System (ADS)

Constantinescu, B.; Ivanov, E. A.; Pascovici, G.; Popa-Simil, L.; Racolta, P. M.

1994-05-01

The Thin Layer Activation (TLA) technique is a nuclear method especially used for different types of wear (or corrosion) investigations. Experimental results for selection criteria of nuclear reactions for various tribological studies, using the IPNE U-120 classical variable energy Cyclotron are presented. Measuring methods for the main types of wear phenomena and home made instrumentations dedicated for TLA industrial applications are also reported. Some typical TLA tribological applications, a nuclear scanning method to obtain wear profile of piston-rings are presented as well.

Nuclear Science Teaching Aids and Activities.

ERIC Educational Resources Information Center

Woodburn, John H.

This publication is a sourcebook for science teachers. It provides guides for basic laboratory work in nuclear energy, suggesting various teacher and student demonstrations. Ideas for science clubs, science fairs, and project research seminars are presented. Problem-solving activities for both science and mathematics classes are included, as well…

10 CFR 4.510 - Self-evaluation.

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Nuclear data activities at the n_TOF facility at CERN

NASA Astrophysics Data System (ADS)

Gunsing, F.; Aberle, O.; Andrzejewski, J.; Audouin, L.; Bécares, V.; Bacak, M.; Balibrea-Correa, J.; Barbagallo, M.; Barros, S.; Bečvář, F.; Beinrucker, C.; Belloni, F.; Berthoumieux, E.; Billowes, J.; Bosnar, D.; Brugger, M.; Caamaño, M.; Calviño, F.; Calviani, M.; Cano-Ott, D.; Cardella, R.; Casanovas, A.; Castelluccio, D. M.; Cerutti, F.; Chen, Y. H.; Chiaveri, E.; Colonna, N.; Cortés-Giraldo, M. A.; Cortés, G.; Cosentino, L.; Damone, L. A.; Deo, K.; Diakaki, M.; Domingo-Pardo, C.; Dressler, R.; Dupont, E.; Durán, I.; Fernández-Domínguez, B.; Ferrari, A.; Ferreira, P.; Finocchiaro, P.; Frost, R. J. W.; Furman, V.; Ganesan, S.; García, A. R.; Gawlik, A.; Gheorghe, I.; Glodariu, T.; Gonçalves, I. F.; González, E.; Goverdovski, A.; Griesmayer, E.; Guerrero, C.; Göbel, K.; Harada, H.; Heftrich, T.; Heinitz, S.; Hernández-Prieto, A.; Heyse, J.; Jenkins, D. G.; Jericha, E.; Käppeler, F.; Kadi, Y.; Katabuchi, T.; Kavrigin, P.; Ketlerov, V.; Khryachkov, V.; Kimura, A.; Kivel, N.; Kokkoris, M.; Krtička, M.; Leal-Cidoncha, E.; Lederer, C.; Leeb, H.; Lerendegui, J.; Licata, M.; Lo Meo, S.; Lonsdale, S. J.; Losito, R.; Macina, D.; Marganiec, J.; Martínez, T.; Masi, A.; Massimi, C.; Mastinu, P.; Mastromarco, M.; Matteucci, F.; Maugeri, E. A.; Mazzone, A.; Mendoza, E.; Mengoni, A.; Milazzo, P. M.; Mingrone, F.; Mirea, M.; Montesano, S.; Musumarra, A.; Nolte, R.; Oprea, A.; Palomo-Pinto, F. R.; Paradela, C.; Patronis, N.; Pavlik, A.; Perkowski, J.; Porras, I.; Praena, J.; Quesada, J. M.; Rajeev, K.; Rauscher, T.; Reifarth, R.; Riego-Perez, A.; Robles, M.; Rout, P.; Radeck, D.; Rubbia, C.; Ryan, J. A.; Sabaté-Gilarte, M.; Saxena, A.; Schillebeeckx, P.; Schmidt, S.; Schumann, D.; Sedyshev, P.; Smith, A. G.; Stamatopoulos, A.; Suryanarayana, S. V.; Tagliente, G.; Tain, J. L.; Tarifeño-Saldivia, A.; Tarrío, D.; Tassan-Got, L.; Tsinganis, A.; Valenta, S.; Vannini, G.; Variale, V.; Vaz, P.; Ventura, A.; Vlachoudis, V.; Vlastou, R.; Wallner, A.; Warren, S.; Weigand, M.; Weiss, C.; Wolf, C.; Woods, P. J.; Wright, T.; Žugec, P.

2016-10-01

Nuclear data in general, and neutron-induced reaction cross sections in particular, are important for a wide variety of research fields. They play a key role in the safety and criticality assessment of nuclear technology, not only for existing power reactors but also for radiation dosimetry, medical applications, the transmutation of nuclear waste, accelerator-driven systems, fuel cycle investigations and future reactor systems as in Generation IV. Applications of nuclear data are also related to research fields as the study of nuclear level densities and stellar nucleosynthesis. Simulations and calculations of nuclear technology applications largely rely on evaluated nuclear data libraries. The evaluations in these libraries are based both on experimental data and theoretical models. Experimental nuclear reaction data are compiled on a worldwide basis by the international network of Nuclear Reaction Data Centres (NRDC) in the EXFOR database. The EXFOR database forms an important link between nuclear data measurements and the evaluated data libraries. CERN's neutron time-of-flight facility n_TOF has produced a considerable amount of experimental data since it has become fully operational with the start of the scientific measurement programme in 2001. While for a long period a single measurement station (EAR1) located at 185 m from the neutron production target was available, the construction of a second beam line at 20 m (EAR2) in 2014 has substantially increased the measurement capabilities of the facility. An outline of the experimental nuclear data activities at CERN's neutron time-of-flight facility n_TOF will be presented.

Dual function of the nuclear export signal of the Borna disease virus nucleoprotein in nuclear export activity and binding to viral phosphoprotein.

PubMed

Yanai, Mako; Sakai, Madoka; Makino, Akiko; Tomonaga, Keizo

2017-07-11

Borna disease virus (BoDV), which has a negative-sense, single-stranded RNA genome, causes persistent infection in the cell nucleus. The nuclear export signal (NES) of the viral nucleoprotein (N) consisting of leucine at positions 128 and 131 and isoleucine at positions 133 and 136 overlaps with one of two predicted binding sites for the viral phosphoprotein (P). A previous study demonstrated that higher expression of BoDV-P inhibits nuclear export of N; however, the function of N NES in the interaction with P remains unclear. We examined the subcellular localization, viral polymerase activity, and P-binding ability of BoDV-N NES mutants. We also characterized a recombinant BoDV (rBoDV) harboring an NES mutation of N. BoDV-N with four alanine-substitutions in the leucine and isoleucine residues of the NES impaired its cytoplasmic localization and abolished polymerase activity and P-binding ability. Although an alanine-substitution at position 131 markedly enhanced viral polymerase activity as determined by a minigenome assay, rBoDV harboring this mutation showed expression of viral RNAs and proteins relative to that of wild-type rBoDV. Our results demonstrate that BoDV-N NES has a dual function in BoDV replication, i.e., nuclear export of N and an interaction with P, affecting viral polymerase activity in the nucleus.

Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harnicarova, Andrea; Kozubek, Stanislav; Pachernik, Jiri

2006-12-10

Using sequential RNA-DNA fluorescence in situ hybridization, the nuclear arrangement of both the active and inactive c-myc gene as well as its transcription was investigated in colon cancer HT-29 cells induced to differentiate into enterocytes. Cytogenetic studies revealed the presence of two chromosomes 8 in HT-29 cells, of which the one containing c-myc gene amplicons was substantially larger and easily distinguished from the normal chromosome. This observation enabled detection of both activity and nuclear localization of c-myc genes in single cells and in individual chromosome territories. Similar transcriptional activity of the c-myc gene was observed in both the normal andmore » derivative chromosome 8 territories showing no influence of the amplification on the c-myc gene expression. Our experiments demonstrate strikingly specific nuclear and territorial arrangements of active genes as compared with inactive ones: on the periphery of their territories facing to the very central region of the cell nucleus. Nuclear arrangement of c-myc genes and transcripts was conserved during cell differentiation and, therefore, independent of the level of differentiation-specific c-myc gene expression. However, after the induction of differentiation, a more internal territorial location was found for the single copy c-myc gene of normal chromosome 8, while amplicons conserved their territorial topography.« less

Nuclear Function of Smad7 Promotes Myogenesis▿

PubMed Central

Miyake, Tetsuaki; Alli, Nezeka S.; McDermott, John C.

2010-01-01

In the “canonical” view of transforming growth factor β (TGF-β) signaling, Smad7 plays an inhibitory role. While Smad7 represses Smad3 activation by TGF-β, it does not reverse the inhibitory effect of TGF-β on myogenesis, suggesting a different function in myogenic cells. We previously reported a promyogenic role of Smad7 mediated by an interaction with MyoD. Based on this association, we hypothesized a possible nuclear function of Smad7 independent of its role at the level of the receptor. We therefore engineered a chimera of Smad7 with a nuclear localization signal (NLS), which serves to prevent and therefore bypass binding to the TGF-β receptor while concomitantly constitutively localizing Smad7 to the nucleus. This Smad7-NLS did not repress Smad3 activation by TGF-β but did retain its ability to enhance myogenic gene activation and phenotypic myogenesis, indicating that the nuclear, receptor-independent function of Smad7 is sufficient to promote myogenesis. Furthermore, Smad7 physically interacts with MyoD and antagonizes the repressive effects of active MEK on MyoD. Reporter and myogenic conversion assays indicate a pivotal regulation of MyoD transcriptional properties by the balance between Smad7 and active MEK. Thus, Smad7 has a nuclear coactivator function that is independent of TGF-β signaling and necessary to promote myogenic differentiation. PMID:19995910

Balanced nuclear and cytoplasmic activities of EDS1 are required for a complete plant innate immune response.

PubMed

García, Ana V; Blanvillain-Baufumé, Servane; Huibers, Robin P; Wiermer, Marcel; Li, Guangyong; Gobbato, Enrico; Rietz, Steffen; Parker, Jane E

2010-07-01

An important layer of plant innate immunity to host-adapted pathogens is conferred by intracellular nucleotide-binding/oligomerization domain-leucine rich repeat (NB-LRR) receptors recognizing specific microbial effectors. Signaling from activated receptors of the TIR (Toll/Interleukin-1 Receptor)-NB-LRR class converges on the nucleo-cytoplasmic immune regulator EDS1 (Enhanced Disease Susceptibility1). In this report we show that a receptor-stimulated increase in accumulation of nuclear EDS1 precedes or coincides with the EDS1-dependent induction and repression of defense-related genes. EDS1 is capable of nuclear transport receptor-mediated shuttling between the cytoplasm and nucleus. By enhancing EDS1 export from inside nuclei (through attachment of an additional nuclear export sequence (NES)) or conditionally releasing EDS1 to the nucleus (by fusion to a glucocorticoid receptor (GR)) in transgenic Arabidopsis we establish that the EDS1 nuclear pool is essential for resistance to biotrophic and hemi-biotrophic pathogens and for transcriptional reprogramming. Evidence points to post-transcriptional processes regulating receptor-triggered accumulation of EDS1 in nuclei. Changes in nuclear EDS1 levels become equilibrated with the cytoplasmic EDS1 pool and cytoplasmic EDS1 is needed for complete resistance and restriction of host cell death at infection sites. We propose that coordinated nuclear and cytoplasmic activities of EDS1 enable the plant to mount an appropriately balanced immune response to pathogen attack.

Nerve growth factor (NGF) regulates activity of nuclear factor of activated T-cells (NFAT) in neurons via the phosphatidylinositol 3-kinase (PI3K)-Akt-glycogen synthase kinase 3β (GSK3β) pathway.

PubMed

Kim, Man-Su; Shutov, Leonid P; Gnanasekaran, Aswini; Lin, Zhihong; Rysted, Jacob E; Ulrich, Jason D; Usachev, Yuriy M

2014-11-07

The Ca(2+)/calcineurin-dependent transcription factor nuclear factor of activated T-cells (NFAT) plays an important role in regulating many neuronal functions, including excitability, axonal growth, synaptogenesis, and neuronal survival. NFAT can be activated by action potential firing or depolarization that leads to Ca(2+)/calcineurin-dependent dephosphorylation of NFAT and its translocation to the nucleus. Recent data suggest that NFAT and NFAT-dependent functions in neurons can also be potently regulated by NGF and other neurotrophins. However, the mechanisms of NFAT regulation by neurotrophins are not well understood. Here, we show that in dorsal root ganglion sensory neurons, NGF markedly facilitates NFAT-mediated gene expression induced by mild depolarization. The effects of NGF were not associated with changes in [Ca(2+)]i and were independent of phospholipase C activity. Instead, the facilitatory effect of NGF depended on activation of the PI3K/Akt pathway downstream of the TrkA receptor and on inhibition of glycogen synthase kinase 3β (GSK3β), a protein kinase known to phosphorylate NFAT and promote its nuclear export. Knockdown or knockout of NFATc3 eliminated this facilitatory effect. Simultaneous monitoring of EGFP-NFATc3 nuclear translocation and [Ca(2+)]i changes in dorsal root ganglion neurons indicated that NGF slowed the rate of NFATc3 nuclear export but did not affect its nuclear import rate. Collectively, our data suggest that NGF facilitates depolarization-induced NFAT activation by stimulating PI3K/Akt signaling, inactivating GSK3β, and thereby slowing NFATc3 export from the nucleus. We propose that NFAT serves as an integrator of neurotrophin action and depolarization-driven calcium signaling to regulate neuronal gene expression. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Nerve Growth Factor (NGF) Regulates Activity of Nuclear Factor of Activated T-cells (NFAT) in Neurons via the Phosphatidylinositol 3-Kinase (PI3K)-Akt-Glycogen Synthase Kinase 3β (GSK3β) Pathway*

PubMed Central

Kim, Man-Su; Shutov, Leonid P.; Gnanasekaran, Aswini; Lin, Zhihong; Rysted, Jacob E.; Ulrich, Jason D.; Usachev, Yuriy M.

2014-01-01

The Ca2+/calcineurin-dependent transcription factor nuclear factor of activated T-cells (NFAT) plays an important role in regulating many neuronal functions, including excitability, axonal growth, synaptogenesis, and neuronal survival. NFAT can be activated by action potential firing or depolarization that leads to Ca2+/calcineurin-dependent dephosphorylation of NFAT and its translocation to the nucleus. Recent data suggest that NFAT and NFAT-dependent functions in neurons can also be potently regulated by NGF and other neurotrophins. However, the mechanisms of NFAT regulation by neurotrophins are not well understood. Here, we show that in dorsal root ganglion sensory neurons, NGF markedly facilitates NFAT-mediated gene expression induced by mild depolarization. The effects of NGF were not associated with changes in [Ca2+]i and were independent of phospholipase C activity. Instead, the facilitatory effect of NGF depended on activation of the PI3K/Akt pathway downstream of the TrkA receptor and on inhibition of glycogen synthase kinase 3β (GSK3β), a protein kinase known to phosphorylate NFAT and promote its nuclear export. Knockdown or knockout of NFATc3 eliminated this facilitatory effect. Simultaneous monitoring of EGFP-NFATc3 nuclear translocation and [Ca2+]i changes in dorsal root ganglion neurons indicated that NGF slowed the rate of NFATc3 nuclear export but did not affect its nuclear import rate. Collectively, our data suggest that NGF facilitates depolarization-induced NFAT activation by stimulating PI3K/Akt signaling, inactivating GSK3β, and thereby slowing NFATc3 export from the nucleus. We propose that NFAT serves as an integrator of neurotrophin action and depolarization-driven calcium signaling to regulate neuronal gene expression. PMID:25231981

10 CFR 70.22 - Contents of applications.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 2 2011-01-01 2011-01-01 false Contents of applications. 70.22 Section 70.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR MATERIAL License... alien, foreign corporation, or foreign government; (2) The activity for which the special nuclear...

10 CFR 70.22 - Contents of applications.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Contents of applications. 70.22 Section 70.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR MATERIAL License... alien, foreign corporation, or foreign government; (2) The activity for which the special nuclear...

10 CFR 70.22 - Contents of applications.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 2 2013-01-01 2013-01-01 false Contents of applications. 70.22 Section 70.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR MATERIAL License... alien, foreign corporation, or foreign government; (2) The activity for which the special nuclear...

10 CFR 70.22 - Contents of applications.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 2 2014-01-01 2014-01-01 false Contents of applications. 70.22 Section 70.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR MATERIAL License... alien, foreign corporation, or foreign government; (2) The activity for which the special nuclear...

10 CFR 70.22 - Contents of applications.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 2 2012-01-01 2012-01-01 false Contents of applications. 70.22 Section 70.22 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING OF SPECIAL NUCLEAR MATERIAL License... alien, foreign corporation, or foreign government; (2) The activity for which the special nuclear...

Analysis of the resilience of team performance during a nuclear emergency response exercise.

PubMed

Gomes, José Orlando; Borges, Marcos R S; Huber, Gilbert J; Carvalho, Paulo Victor R

2014-05-01

The current work presents results from a cognitive task analysis (CTA) of a nuclear disaster simulation. Audio-visual records were collected from an emergency room team composed of individuals from 26 different agencies as they responded to multiple scenarios in a simulated nuclear disaster. This simulation was part of a national emergency response training activity for a nuclear power plant located in a developing country. The objectives of this paper are to describe sources of resilience and brittleness in these activities, identify cues of potential improvements for future emergency simulations, and leveraging the resilience of the emergency response system in case of a real disaster. Multiple CTA techniques were used to gain a better understanding of the cognitive dimensions of the activity and to identify team coordination and crisis management patterns that emerged from the simulation exercises. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

131I INTERNAL CONTAMINATION AND COMMITTED DOSE ASSESSMENT AMONG NUCLEAR MEDICINE MEDICAL PERSONNEL.

PubMed

Brudecki, K; Kluczewska-Galka, A; Mróz, T; Jarzab, B; Zagrodzki, P; Janowski, P

2018-05-01

This study presents 131I thyroid activity measurements of 56 employees of the Department of Nuclear Medicine and Endocrine Oncology, Centre for Oncology in Gliwice. The research instrument was a whole-body spectrometer. In 44 out of 56 examined staff members, the determined 131I activity was found to be above the detection limit. The measured activities ranged from 6 ± 2 to 457 ± 118 Bq. The maximum estimated committed effective dose reached was 1.5 mSv/y. The results were compared with previous measurements conducted in another Polish nuclear medical unit. From this comparison, we can see that radiological safety among nuclear medicine personnel can be improved by appropriate work organisation. Reducing exposure of workers can be achieved by properly organised turnovers concerning the most vulnerable worksites. In addition, to lower the radiation risk, it is essential to comply strictly with the isolation regime for the patients.

OFF-SITE ENVIRONMENTAL MONITORING REPORT: RADIATION MONITORING AROUND UNITED STATES NUCLEAR TEST AREAS, CALENDAR YEAR 1986

EPA Science Inventory

The principal activity at the NTS is testing of nuclear devices, though other related projects are also conducted. The principal activities of the Off-Site Radiological Safety Program are routine environmental monitoring for radioactive materials in various media and for radiatio...

75 FR 66394 - Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-28

... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2010-0262] Agency Information Collection Activities: Submission for the Office of Management and Budget (OMB) Review; Comment Request AGENCY: Nuclear Regulatory.... 10. Abstract: NRC Form 4 is used to record the summary of a radiation worker's cumulative...

10 CFR 820.11 - Information requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Information requirements. 820.11 Section 820.11 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES General § 820.11 Information requirements. (a) Any information pertaining to a nuclear activity provided to DOE by any person or maintained by...

Learning Activity Package, Physical Science. LAP Numbers 8, 9, 10, and 11.

ERIC Educational Resources Information Center

Williams, G. J.

These four units of the Learning Activity Packages (LAPs) for individualized instruction in physical science cover nuclear reactions, alpha and beta particles, atomic radiation, medical use of nuclear energy, fission, fusion, simple machines, Newton's laws of motion, electricity, currents, electromagnetism, Oersted's experiment, sound, light,…

10 CFR 4.541-4.548 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.541-4.548 Section 4.541-4.548 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.541-4.548 [Reserved] ...

10 CFR 4.552-4.559 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.552-4.559 Section 4.552-4.559 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.552-4.559 [Reserved] ...

10 CFR 4.504-4.509 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.504-4.509 Section 4.504-4.509 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.504-4.509 [Reserved] ...

10 CFR 4.531-4.539 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.531-4.539 Section 4.531-4.539 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.531-4.539 [Reserved] ...

10 CFR 4.561-4.569 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.561-4.569 Section 4.561-4.569 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.561-4.569 [Reserved] ...

10 CFR 4.512-4.529 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.512-4.529 Section 4.512-4.529 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.512-4.529 [Reserved] ...

10 CFR 4.571-4.999 - [Reserved

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false [Reserved] 4.571-4.999 Section 4.571-4.999 Energy NUCLEAR REGULATORY COMMISSION NONDISCRIMINATION IN FEDERALLY ASSISTED PROGRAMS OR ACTIVITIES RECEIVING FEDERAL... Programs or Activities Conducted by the U.S. Nuclear Regulatory Commission §§ 4.571-4.999 [Reserved] ...

IMPORTANCE OF GLUTATHIONE IN THE ACQUISITION AND MAINTENANCE OF SPERM NUCLEAR DECONDENSING ACTIVITY IN MATURING HAMSTER OOCYTES

EPA Science Inventory

Sperm nuclear decondensing activity in mammalian oocytes is dependent upon the maturational state of the oocyte. It is maximal in mature, metaphase II oocytes and minimal or absent in immature germinal vesicle (GV) and fertilized pronuclear oocytes. Previous studies suggested tha...

10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Evidentiary matters. 820.8 Section 820.8 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES General § 820.8 Evidentiary matters. (a... matter related to a DOE nuclear activity or for any decision required by this part. A DOE Official may...

10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Evidentiary matters. 820.8 Section 820.8 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES General § 820.8 Evidentiary matters. (a... matter related to a DOE nuclear activity or for any decision required by this part. A DOE Official may...

10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Evidentiary matters. 820.8 Section 820.8 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES General § 820.8 Evidentiary matters. (a... matter related to a DOE nuclear activity or for any decision required by this part. A DOE Official may...

10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Evidentiary matters. 820.8 Section 820.8 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES General § 820.8 Evidentiary matters. (a... matter related to a DOE nuclear activity or for any decision required by this part. A DOE Official may...

10 CFR 820.8 - Evidentiary matters.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Evidentiary matters. 820.8 Section 820.8 Energy DEPARTMENT OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES General § 820.8 Evidentiary matters. (a... matter related to a DOE nuclear activity or for any decision required by this part. A DOE Official may...

10 CFR 830.2 - Exclusions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Exclusions. 830.2 Section 830.2 Energy DEPARTMENT OF ENERGY NUCLEAR SAFETY MANAGEMENT § 830.2 Exclusions. This part does not apply to: (a) Activities that are... 1974, as amended; and (e) Activities related to the launch approval and actual launch of nuclear energy...

10 CFR 830.2 - Exclusions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Exclusions. 830.2 Section 830.2 Energy DEPARTMENT OF ENERGY NUCLEAR SAFETY MANAGEMENT § 830.2 Exclusions. This part does not apply to: (a) Activities that are... 1974, as amended; and (e) Activities related to the launch approval and actual launch of nuclear energy...

10 CFR 830.2 - Exclusions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Exclusions. 830.2 Section 830.2 Energy DEPARTMENT OF ENERGY NUCLEAR SAFETY MANAGEMENT § 830.2 Exclusions. This part does not apply to: (a) Activities that are... 1974, as amended; and (e) Activities related to the launch approval and actual launch of nuclear energy...

10 CFR 830.2 - Exclusions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Exclusions. 830.2 Section 830.2 Energy DEPARTMENT OF ENERGY NUCLEAR SAFETY MANAGEMENT § 830.2 Exclusions. This part does not apply to: (a) Activities that are... 1974, as amended; and (e) Activities related to the launch approval and actual launch of nuclear energy...

10 CFR 830.2 - Exclusions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Exclusions. 830.2 Section 830.2 Energy DEPARTMENT OF ENERGY NUCLEAR SAFETY MANAGEMENT § 830.2 Exclusions. This part does not apply to: (a) Activities that are... 1974, as amended; and (e) Activities related to the launch approval and actual launch of nuclear energy...

Nuclear Theft: Real and Imagined Dangers

DTIC Science & Technology

1976-03-01

are utilized in connection with fossil fuel energy research and development programs and related activities conducted by the Bureau of Mines "energy... development associated with the U.S. nuclear weapons program . Addition- ally, ERDA conducts related programs which include power reactor design... development , nuclear propulsion, and other systems associated with space programs . The military and ERDA enjoy a symbiotic relationship in that nuclear

Science, Society, and America's Nuclear Waste: Nuclear Waste, Unit 1. Teacher Guide. Second Edition.

ERIC Educational Resources Information Center

Department of Energy, Washington, DC. Office of Civilian Radioactive Waste Management, Washington, DC.

This guide is Unit 1 of the four-part series Science, Society, and America's Nuclear Waste produced by the U.S. Department of Energy's Office of Civilian Radioactive Waste Management. The goal of this unit is to help students establish the relevance of the topic of nuclear waste to their everyday lives and activities. Particular attention is…

Nuclear rocket propulsion technology - A joint NASA/DOE project

NASA Technical Reports Server (NTRS)

Clark, John S.

1991-01-01

NASA and the DOE have initiated critical technology development for nuclear rocket propulsion systems for SEI human and robotic missions to the moon and to Mars. The activities and project plan of the interagency project planning team in FY 1990 and 1991 are summarized. The project plan includes evolutionary technology development for both nuclear thermal and nuclear electric propulsion systems.

75 FR 59158 - Earth Day Commitment/Friends of the Coast, Beyond Nuclear, Seacoast Anti-Pollution League, C-10...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... state that active proposals for more than 3,000 megawatts of wind power are currently on the books in... projected over 20 years what wind power will then be available, in part because wind power projects are... public about the connections between nuclear power and nuclear weapons. Beyond Nuclear has members who...

Localization of proteasomes and proteasomal proteolysis in the mammalian interphase cell nucleus by systematic application of immunocytochemistry.

PubMed

Scharf, Andrea; Rockel, Thomas Dino; von Mikecz, Anna

2007-06-01

Proteasomes are ATP-driven, multisubunit proteolytic machines that degrade endogenous proteins into peptides and play a crucial role in cellular events such as the cell cycle, signal transduction, maintenance of proper protein folding and gene expression. Recent evidence indicates that the ubiquitin-proteasome system is an active component of the cell nucleus. A characteristic feature of the nucleus is its organization into distinct domains that have a unique composition of macromolecules and dynamically form as a response to the requirements of nuclear function. Here, we show by systematic application of different immunocytochemical procedures and comparison with signature proteins of nuclear domains that during interphase endogenous proteasomes are localized diffusely throughout the nucleoplasm, in speckles, in nuclear bodies, and in nucleoplasmic foci. Proteasomes do not occur in the nuclear envelope region or the nucleolus, unless nucleoplasmic invaginations expand into this nuclear body. Confirmedly, proteasomal proteolysis is detected in nucleoplasmic foci, but is absent from the nuclear envelope or nucleolus. The results underpin the idea that the ubiquitin-proteasome system is not only located, but also proteolytically active in distinct nuclear domains and thus may be directly involved in gene expression, and nuclear quality control.

Cdk1 Activates Pre-mitotic Nuclear Envelope Dynein Recruitment and Apical Nuclear Migration in Neural Stem Cells.

PubMed

Baffet, Alexandre D; Hu, Daniel J; Vallee, Richard B

2015-06-22

Dynein recruitment to the nuclear envelope is required for pre-mitotic nucleus-centrosome interactions in nonneuronal cells and for apical nuclear migration in neural stem cells. In each case, dynein is recruited to the nuclear envelope (NE) specifically during G2 via two nuclear pore-mediated mechanisms involving RanBP2-BicD2 and Nup133-CENP-F. The mechanisms responsible for cell-cycle control of this behavior are unknown. We now find that Cdk1 serves as a direct master controller for NE dynein recruitment in neural stem cells and HeLa cells. Cdk1 phosphorylates conserved sites within RanBP2 and activates BicD2 binding and early dynein recruitment. Late recruitment is triggered by a Cdk1-induced export of CENP-F from the nucleus. Forced NE targeting of BicD2 overrides Cdk1 inhibition, fully rescuing dynein recruitment and nuclear migration in neural stem cells. These results reveal how NE dynein recruitment is cell-cycle regulated and identify the trigger mechanism for apical nuclear migration in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Iso standardization of theoretical activity evaluation method for low and intermediate level activated waste generated at nuclear power plants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Makoto Kashiwagi; Garamszeghy, Mike; Lantes, Bertrand

Disposal of low-and intermediate-level activated waste generated at nuclear power plants is being planned or carried out in many countries. The radioactivity concentrations and/or total quantities of long-lived, difficult-to-measure nuclides (DTM nuclides), such as C-14, Ni-63, Nb-94, α emitting nuclides etc., are often restricted by the safety case for a final repository as determined by each country's safety regulations, and these concentrations or amounts are required to be known and declared. With respect to waste contaminated by contact with process water, the Scaling Factor method (SF method), which is empirically based on sampling and analysis data, has been applied asmore » an important method for determining concentrations of DTM nuclides. This method was standardized by the International Organization for Standardization (ISO) and published in 2007 as ISO21238 'Scaling factor method to determine the radioactivity of low and intermediate-level radioactive waste packages generated at nuclear power plants' [1]. However, for activated metal waste with comparatively high concentrations of radioactivity, such as may be found in reactor control rods and internal structures, direct sampling and radiochemical analysis methods to evaluate the DTM nuclides are limited by access to the material and potentially high personnel radiation exposure. In this case, theoretical calculation methods in combination with empirical methods based on remote radiation surveys need to be used to best advantage for determining the disposal inventory of DTM nuclides while minimizing exposure to radiation workers. Pursuant to this objective a standard for the theoretical evaluation of the radioactivity concentration of DTM nuclides in activated waste, is in process through ISO TC85/SC5 (ISO Technical Committee 85: Nuclear energy, nuclear technologies, and radiological protection; Subcommittee 5: Nuclear fuel cycle). The project team for this ISO standard was formed in 2011 and is composed of experts from 11 countries. The project team has been conducting technical discussions on theoretical methods for determining concentrations of radioactivity, and has developed the draft International Standard of ISO16966 'Theoretical activation calculation method to evaluate the radioactivity of activated waste generated at nuclear reactors' [2]. This paper describes the international standardization process developed by the ISO project team, and outlines the following two theoretical activity evaluation methods:? Point method? Range method. (authors)« less

Telomere-surrounding regions are transcription-permissive 3D nuclear compartments in human cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quina, Ana Sofia; Instituto Gulbenkian de Ciencia, 2781-901 Oeiras; Parreira, Leonor

2005-07-01

Positioning of genes relative to nuclear heterochromatic compartments is thought to help regulate their transcriptional activity. Given that human subtelomeric regions are rich in highly expressed genes, we asked whether human telomeres are related to transcription-permissive nuclear compartments. To address this question, we investigated in the nuclei of normal human lymphocytes the spatial relations of two constitutively expressed genes (ACTB and RARA) and three nuclear transcripts (ACTB, IL2RA and TCRB) to telomeres and centromeres, as a function of gene activity and transcription levels. We observed that genes and gene transcripts locate close to telomere clusters and away from chromocenters uponmore » activation of transcription. These findings, together with the observation that SC35 domains, which are enriched in pre-mRNA processing factors, are in close proximity to telomeres, indicate that telomere-neighboring regions are permissive to gene expression in human cells. Therefore, the associations of telomeres observed in the interphase nucleus might contribute, as opposed to chromocenters, for the establishment of transcription-permissive 3D nuclear compartments.« less

Cloning of the transgenic pigs expressing human decay accelerating factor and N-acetylglucosaminyltransferase III.

PubMed

Fujimura, Tatsuya; Kurome, Mayuko; Murakami, Hiroshi; Takahagi, Yoichi; Matsunami, Katsuyoshi; Shimanuki, Shinichi; Suzuki, Kohei; Miyagawa, Shuji; Shirakura, Ryota; Shigehisa, Tamotsu; Nagashima, Hiroshi

2004-01-01

The present paper describes production of cloned pigs from fibroblast cells of transgenic pigs expressing human decay accelerating factor (DAF, CD55) and N-acetylglucosaminyltransferase III (GnT-III) that remodels sugar-chain biosynthesis. Two nuclear transfer protocols were used: a two-step activation (TA) method and a delayed activation (DA) method. Enucleated in vitro-matured oocytes and donor cells were electrically fused in a calcium-containing medium by TA method or in a calcium-free medium by DA method, followed by electrical activation 1-1.5 h later, respectively. In vitro blastocyst formation rates of nuclear transferred embryos reconstructed by TA and DA method were 8% and 14%, respectively. As a result of embryo transfer of the reconstructed embryos made by each method into recipient pigs, both gave rise to cloned piglets. These cloned pigs expressed transgene as much as their nuclear donor cells. In conclusions, (1) pig cloning can be carried out by TA or DA nuclear transfer methods, (2) expression of transgenes can be maintained to cloned pigs from the nuclear donor cells derived from transgenic animals.

Modulation of NRF2 signaling pathway by nuclear receptors: implications for cancer.

PubMed

Namani, Akhileshwar; Li, Yulong; Wang, Xiu Jun; Tang, Xiuwen

2014-09-01

Nuclear factor-erythroid 2 p45-related factor 2 (NRF2, also known as Nfe2l2) plays a critical role in regulating cellular defense against electrophilic and oxidative stress by activating the expression of an array of antioxidant response element-dependent genes. On one hand, NRF2 activators have been used in clinical trials for cancer prevention and the treatment of diseases associated with oxidative stress; on the other hand, constitutive activation of NRF2 in many types of tumors contributes to the survival and growth of cancer cells, as well as resistance to anticancer therapy. In this review, we provide an overview of the NRF2 signaling pathway and discuss its role in carcinogenesis. We also introduce the inhibition of NRF2 by nuclear receptors. Further, we address the biological significance of regulation of the NRF2 signaling pathway by nuclear receptors in health and disease. Finally, we discuss the possible impact of NRF2 inhibition by nuclear receptors on cancer therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Radiation sensors for medical, industrial and environmental applications: how to engage with schools and the general public

NASA Astrophysics Data System (ADS)

Seitz, B.; Campos Rivera, N.; Gray, R.; Powell, A.; Thomson, F.

2018-01-01

Radiation, radiation detection and radiation protection are topics in physics and its applications which generate a wide interest in the public. This interest is either generated through medical procedures, applications of nuclear energy or nuclear accidents. The technical nature of these topics usually means that they are not well covered in the normal education stream, opening many opportunities to engage with schools and the general public to showcase the latest developments and their applications. The detection of radiation is at the very heart of understanding radiation, its fascination and associated fears. The outreach group of the nuclear physics group at the University of Glasgow demonstrates a number of successful outreach activities centred around radiation detection and described in this paper, focusing on activities delivered to a variety of audiences and related to applied nuclear physics work within our group. These concentrate on the application of novel sensor technologies for nuclear decommissioning, medical imaging modalities and the monitoring of environmental radioactivity. The paper will provide some necessary background material as well as practical instructions for some of the activities developed.

The Cell Nucleus Serves as a Mechanotransducer of Tissue Damage-Induced Inflammation.

PubMed

Enyedi, Balázs; Jelcic, Mark; Niethammer, Philipp

2016-05-19

Tissue damage activates cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (AA), which is oxidized to proinflammatory eicosanoids by 5-lipoxygenase (5-LOX) on the nuclear envelope. How tissue damage is sensed to activate cPLA2 is unknown. We investigated this by live imaging in wounded zebrafish larvae, where damage of the fin tissue causes osmotic cell swelling at the wound margin and the generation of a chemotactic eicosanoid signal. Osmotic swelling of cells and their nuclei activates cPla2 by translocating it from the nucleoplasm to the nuclear envelope. Elevated cytosolic Ca(2+) was necessary but not sufficient for cPla2 translocation, and nuclear swelling was required in parallel. cPla2 translocation upon nuclear swelling was reconstituted in isolated nuclei and appears to be a simple physical process mediated by tension in the nuclear envelope. Our data suggest that the nucleus plays a mechanosensory role in inflammation by transducing cell swelling and lysis into proinflammatory eicosanoid signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

The locus control region is required for association of the murine β-globin locus with engaged transcription factories during erythroid maturation

PubMed Central

Ragoczy, Tobias; Bender, M.A.; Telling, Agnes; Byron, Rachel; Groudine, Mark

2006-01-01

We have examined the relationship between nuclear localization and transcriptional activity of the endogenous murine β-globin locus during erythroid differentiation. Murine fetal liver cells were separated into distinct erythroid maturation stages by fluorescence-activated cell sorting, and the nuclear position of the locus was determined at each stage. We find that the β-globin locus progressively moves away from the nuclear periphery with increasing maturation. Contrary to the prevailing notion that the nuclear periphery is a repressive compartment in mammalian cells, βmajor-globin expression begins at the nuclear periphery prior to relocalization. However, relocation of the locus to the nuclear interior with maturation is accompanied by an increase in βmajor-globin transcription. The distribution of nuclear polymerase II (Pol II) foci also changes with erythroid differentiation: Transcription factories decrease in number and contract toward the nuclear interior. Moreover, both efficient relocalization of the β-globin locus from the periphery and its association with hyperphosphorylated Pol II transcription factories require the locus control region (LCR). These results suggest that the LCR-dependent association of the β-globin locus with transcriptionally engaged Pol II foci provides the driving force for relocalization of the locus toward the nuclear interior during erythroid maturation. PMID:16705039

Structure and Activities of Nuclear Medicine in Kuwait.

PubMed

Elgazzar, Abdelhamid H; Owunwanne, Azuwuike; Alenezi, Saud

2016-07-01

The practice of nuclear medicine in Kuwait began in 1965 as a clinic for treating thyroid diseases. The practice developed gradually and until 1981 when the Faculty of Medicine established the Division of Nuclear Medicine in the Department of Radiology, which later became a separate department responsible for establishing and managing the practice in all hospitals of Kuwait. In 1987, a nuclear medicine residency program was begun and it is administered by Kuwait Institute for Medical Specializations originally as a 4-year but currently as a 5-year program. Currently there are 11 departments in the ministry of health hospitals staffed by 49 qualified attending physicians, mostly the diplomats of the Kuwait Institute for Medical Specializations nuclear medicine residency program, 4 academic physicians, 2 radiopharmacists, 2 physicists, and 130 technologists. These departments are equipped with 33 dual-head gamma cameras, 10 SPET/CT, 5 PET/CT, 2 cyclotrons, 1 breast-specific gamma imaging, 1 positron-emitting mammography, 10 thyroid uptake units, 8 technegas machines, 7 PET infusion systems, and 8 treadmills. Activities of nuclear medicine in Kuwait include education and training, clinical service, and research. Education includes nuclear medicine technology program in the Faculty of Allied Health Sciences, the 5-year residency program, medical school teaching distributed among different modules of the integrated curriculum with 14 didactic lecture, and other teaching sessions in nuclear medicine MSc program, which run concurrently with the first part of the residency program. The team of Nuclear Medicine in Kuwait has been active in research and has published more than 300 paper, 11 review articles, 12 book chapters, and 17 books in addition to 36 grants and 2 patents. A PhD program approved by Kuwait University Council would begin in 2016. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of balance of tritium activity in waste water from nuclear power plants and at selected monitoring sites in the Vltava River, Elbe River and Jihlava (Dyje) River catchments in the Czech Republic.

PubMed

Hanslík, Eduard; Marešová, Diana; Juranová, Eva; Sedlářová, Barbora

2017-12-01

During the routine operation, nuclear power plants discharge waste water containing a certain amount of radioactivity, whose main component is the artificial radionuclide tritium. The amounts of tritium released into the environment are kept within the legal requirements, which minimize the noxious effects of radioactivity, but the activity concentration is well measurable in surface water of the recipient. This study compares amount of tritium activity in waste water from nuclear power plants and the tritium activity detected at selected relevant sites of surface water quality monitoring. The situation is assessed in the catchment of the Vltava and Elbe Rivers, affected by the Temelín Nuclear Power Plant as well as in the Jihlava River catchment (the Danube River catchment respectively), where the waste water of the Dukovany Nuclear Power Plant is discharged. The results show a good agreement of the amount of released tritium stated by the power plant operator and the tritium amount detected in the surface water and highlighted the importance of a robust independent monitoring of tritium discharged from a nuclear power plant which could be carried out by water management authorities. The outputs of independent monitoring allow validating the values reported by a polluter and expand opportunities of using tritium as e.g. tracer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nuclear Forensics and Radiochemistry: Cross Sections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rundberg, Robert S.

The neutron activation of components in a nuclear device can provide useful signatures of weapon design or sophistication. This lecture will cover some of the basics of neutron reaction cross sections. Nuclear reactor cross sections will also be presented to illustrate the complexity of convolving neutron energy spectra with nuclear excitation functions to calculate useful effective reactor cross sections. Deficiencies in the nuclear database will be discussed along with tools available at Los Alamos to provide new neutron cross section data.

Expression of DNAJB12 or DNAJB14 Causes Coordinate Invasion of the Nucleus by Membranes Associated with a Novel Nuclear Pore Structure

PubMed Central

Goodwin, Edward C.; Motamedi, Nasim; Lipovsky, Alex; Fernández-Busnadiego, Rubén; DiMaio, Daniel

2014-01-01

DNAJB12 and DNAJB14 are transmembrane proteins in the endoplasmic reticulum (ER) that serve as co-chaperones for Hsc70/Hsp70 heat shock proteins. We demonstrate that over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, which we designate DJANGOS for DNAJ-associated nuclear globular structures. DJANGOS contain DNAJB12, DNAJB14, Hsc70 and markers of the ER lumen and ER and nuclear membranes. Strikingly, they are evenly distributed underneath the nuclear envelope and are of uniform size in any one nucleus. DJANGOS are composed primarily of single-walled membrane tubes and sheets that connect to the nuclear envelope via a unique configuration of membranes, in which the nuclear pore complex appears anchored exclusively to the outer nuclear membrane, allowing both the inner and outer nuclear membranes to flow past the circumference of the nuclear pore complex into the nucleus. DJANGOS break down rapidly during cell division and reform synchronously in the daughter cell nuclei, demonstrating that they are dynamic structures that undergo coordinate formation and dissolution. Genetic studies showed that the chaperone activity of DNAJ/Hsc70 is required for the formation of DJANGOS. Further analysis of these structures will provide insight into nuclear pore formation and function, activities of molecular chaperones, and mechanisms that maintain membrane identity. PMID:24732912

Clonorchis sinensis excretory-secretory products regulate migration and invasion in cholangiocarcinoma cells via extracellular signal-regulated kinase 1/2/nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

PubMed

Pak, Jhang Ho; Shin, Jimin; Song, In-Sung; Shim, Sungbo; Jang, Sung-Wuk

2017-01-01

Matrix metalloproteinase-9 plays an important role in the invasion and metastasis of various types of cancer cells. We have previously reported that excretory-secretory products from Clonorchis sinensis increases matrix metalloproteinase-9 expression. However, the regulatory mechanisms through which matrix metalloproteinase-9 expression affects cholangiocarcinoma development remain unclear. In the current study, we examined the potential role of excretory-secretory products in regulating the migration and invasion of various cholangiocarcinoma cell lines. We demonstrated that excretory-secretory products significantly induced matrix metalloproteinase-9 expression and activity in a concentration-dependent manner. Reporter gene and chromatin immunoprecipitation assays showed that excretory-secretory products induced matrix metalloproteinase-9 expression by enhancing the activity of nuclear factor-kappa B. Moreover, excretory-secretory products induced the degradation and phosphorylation of IκBα and stimulated nuclear factor-kappa B p65 nuclear translocation, which was regulated by extracellular signal-regulated kinase 1/2. Taken together, our findings indicated that the excretory-secretory product-dependent enhancement of matrix metalloproteinase-9 activity and subsequent induction of IκBα and nuclear factor-kappa B activities may contribute to the progression of cholangiocarcinoma. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

United States Department of Energy, Nevada Operations Office, completion report Operation KLAXON, Fiscal Year 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-06-01

The U.S. Department of Energy, Nevada Operations Office (DOE/NV), Completion Report provides a summary of activities conducted at the Nevada Test Site (NTS) between October 1, 1992, and September 30, 1993, associated with Operation KLAXON. (In the past, each annual Completion Report dealt with a series of underground nuclear detonations; however, because no nuclear tests were conducted during FY 1993, this Report summarizes continuing nonnuclear and nuclear test readiness activities at the NTS sponsored by DOE/NV.) The report serves as a reference for those involved with the planning and execution of Operation KLAXON and also serves as a planning guidemore » for future operations. Information in the report covers the logistics and management of activities. Scientific information and data associated with NTS activities are presented in technical documents published by participating agencies. In September 1992, Congress legislated a nine-month moratorium on the testing of nuclear weapons. The bill also provided for a resumption of testing (with no more than five tests per year, or a total of 15 during the next three years) in July 1993, and mandated an end to nuclear testing, entirely, by 1996. President Bush signed the bill into law in October 1992.« less

A cellular reporter to evaluate CRM1 nuclear export activity: functional analysis of the cancer-related mutant E571K.

PubMed

García-Santisteban, Iraia; Arregi, Igor; Alonso-Mariño, Marián; Urbaneja, María A; Garcia-Vallejo, Juan J; Bañuelos, Sonia; Rodríguez, Jose A

2016-12-01

The exportin CRM1 binds nuclear export signals (NESs), and mediates active transport of NES-bearing proteins from the nucleus to the cytoplasm. Structural and biochemical analyses have uncovered the molecular mechanisms underlying CRM1/NES interaction. CRM1 binds NESs through a hydrophobic cleft, whose open or closed conformation facilitates NES binding and release. Several cofactors allosterically modulate the conformation of the NES-binding cleft through intramolecular interactions involving an acidic loop and a C-terminal helix in CRM1. This current model of CRM1-mediated nuclear export has not yet been evaluated in a cellular setting. Here, we describe SRV100, a cellular reporter to interrogate CRM1 nuclear export activity. Using this novel tool, we provide evidence further validating the model of NES binding and release by CRM1. Furthermore, using both SRV100-based cellular assays and in vitro biochemical analyses, we investigate the functional consequences of a recurrent cancer-related mutation, which targets a residue near CRM1 NES-binding cleft. Our data indicate that this mutation does not necessarily abrogate the nuclear export activity of CRM1, but may increase its affinity for NES sequences bearing a more negatively charged C-terminal end.

Uncoupling of acetylation from phosphorylation regulates FoxO1 function independent of its subcellular localization.

PubMed

Qiang, Li; Banks, Alexander S; Accili, Domenico

2010-08-27

The activity of transcription factor FoxO1 is regulated by phosphorylation-dependent nuclear exclusion and deacetylation-dependent nuclear retention. It is unclear whether and how these two post-translational modifications affect each other. To answer this question, we expressed FoxO1 cDNAs with combined mutations of phosphorylation and acetylation sites in HEK-293 cells and analyzed their subcellular localization patterns. We show that mutations mimicking the acetylated state (KQ series) render FoxO1 more sensitive to Akt-mediated phosphorylation and nuclear exclusion and can reverse the constitutively nuclear localization of phosphorylation-defective FoxO1. Conversely, mutations mimicking the deacetylated state (KR series) promote FoxO1 nuclear retention. Oxidative stress and the Sirt1 activator resveratrol are thought to promote FoxO1 deacetylation and nuclear retention, thus increasing its activity. Accordingly, FoxO1 deacetylation was required for the effect of oxidative stress (induced by H(2)O(2)) to retain FoxO1 in the nucleus. H(2)O(2) also inhibited FoxO1 phosphorylation on Ser-253 and Thr-24, the key insulin-regulated sites, irrespective of its acetylation. In contrast, the effect of resveratrol was independent of FoxO1 acetylation and its phosphorylation on Ser-253 and Thr-24, suggesting that resveratrol acts on FoxO1 in a Sirt1- and Akt-independent manner. The dissociation of deacetylation from dephosphorylation in H(2)O(2)-treated cells indicates that the two modifications can occur independently of each other. It can be envisaged that FoxO1 exists in multiple nuclear forms with distinct activities depending on the balance of acetylation and phosphorylation.

Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and glial cells in aging and stroke.

PubMed

Pirici, Daniel; Pirici, Ionica; Mogoanta, Laurentiu; Margaritescu, Otilia; Tudorica, Valerica; Margaritescu, Claudiu; Ion, Daniela A; Simionescu, Cristiana; Coconu, Marieta

2012-10-01

Matrix metalloproteinases (MMPs) are well-recognized denominators for extracellular matrix remodeling in the pathology of both ischemic and hemorrhagic strokes. Recent data on non-nervous system tissue showed intracellular and even intranuclear localizations for different MMPs, and together with this, a plethora of new functions have been proposed for these intracellular active enzymes, but are mostly related to apoptosis induction and malign transformation. In neurons and glial cells, on human tissue, animal models and cell cultures, different active MMPs have been also proven to be located in the intra-cytoplasmic or intra-nuclear compartments, with no clear-cut function. In the present study we show for the first time on human tissue the nuclear expression of MMP-9, mainly in neurons and to a lesser extent in astrocytes. We have studied ischemic and hemorrhagic stroke patients, as well as aged control patients. Age and ischemic suffering seemed to be the best predictors for an elevated MMP-9 nuclear expression, and there was no evidence of a clear-cut extracellular proteolytic activity for this compartment, as revealed by intact vascular basement membranes and assessment of vascular densities. More, the majority of the cells expressing MMP-9 in the nuclear compartment also co-expressed activated-caspase 3, indicating a possible link between nuclear MMP-9 localization and apoptosis in neuronal and glial cells following an ischemic or hemorrhagic event. These results, besides showing for the first time the nuclear localization of MMP-9 on a large series of human stroke and aged brain tissues, raise new questions regarding the unknown spectrum of the functions MMPs in human CNS pathology. © 2011 Japanese Society of Neuropathology.

Activation of muscarinic receptors in rat parotid acinar cells induces AQP5 trafficking to nuclei and apical plasma membrane.

PubMed

Cho, Gota; Bragiel, Aneta M; Wang, Di; Pieczonka, Tomasz D; Skowronski, Mariusz T; Shono, Masayuki; Nielsen, Søren; Ishikawa, Yasuko

2015-04-01

The subcellular distribution of aquaporin-5 (AQP5) in rat parotid acinar cells in response to muscarinic acetylcholine receptor (mAChR) activation remains unclear. Immunoconfocal and immunoelectron microscopy were used to visualize the distribution of AQP5 in parotid acinar cells. Western blotting was used to analyze AQP5 levels in membranes. To clarify the characteristics of membrane domains associated with AQP5, detergent solubility and sucrose-density flotation experiments were performed. Under control conditions, AQP5 was diffusely distributed on the apical plasma membrane (APM) and apical plasmalemmal region and throughout the cytoplasm. Upon mAChR activation, AQP5 was predominantly located in the nucleus, APM and lateral plasma membrane (LPM). Subsequently, localization of AQP5 in the nucleus, APM and LPM was decreased. Prolonged atropine treatment inhibited mAChR agonist-induced translocation of AQP5 to the nucleus, APM and LPM. AQP5 levels were enhanced in isolated nuclei and nuclear membranes prepared from parotid tissues incubated with mAChR agonist. mAChR agonist induced AQP5 levels in both soluble and insoluble nuclear fractions solubilized with Triton X-100 or Lubrol WX. Small amounts of AQP5 in nuclei were detected using low-density sucrose gradient. When AQP5 was present in the nuclear membrane, nuclear size decreased. The activation of mAChR induced AQP5 translocation to the nucleus, APM and LPM, and AQP5 may trigger water transport across the nuclear membrane and plasma membrane in rat parotid acinar cells. AQP5 translocates to the nuclear membrane and may trigger the movement of water, inducing shrinkage of the nucleus and the start of nuclear functions. Copyright © 2015 Elsevier B.V. All rights reserved.

Activity and subcellular compartmentalization of peroxisome proliferator-activated receptor alpha are altered by the centrosome-associated protein CAP350.

PubMed

Patel, Hansa; Truant, Ray; Rachubinski, Richard A; Capone, John P

2005-01-01

Peroxisome proliferator-activated nuclear hormone receptors (PPAR) are ligand-activated transcription factors that play pivotal roles in governing metabolic homeostasis and cell growth. PPARs are primarily in the nucleus but, under certain circumstances, can be found in the cytoplasm. We show here that PPAR(alpha) interacts with the centrosome-associated protein CAP350. CAP350 also interacts with PPAR(delta), PPAR(gamma) and liver-X-receptor alpha, but not with the 9-cis retinoic acid receptor, RXR(alpha). Immunofluorescence analysis indicated that PPAR(alpha) is diffusely distributed in the nucleus and excluded from the cytoplasm. However, in the presence of coexpressed CAP350, PPAR(alpha) colocalizes with CAP350 to discrete nuclear foci and to the centrosome, perinuclear region and intermediate filaments. In contrast, the subcellular distribution of RXR(alpha) or of thyroid hormone receptor alpha was not altered by coexpression of CAP350. An amino-terminal fragment of CAP350 was localized exclusively to nuclear foci and was sufficient to recruit PPAR(alpha) to these sites. Mutation of the single putative nuclear hormone receptor interacting signature motif LXXLL present in this fragment had no effect on its subnuclear localization but abrogated recruitment of PPAR(alpha) to nuclear foci. Surprisingly, mutation of the LXXLL motif in this CAP350 subfragment did not prevent its binding to PPAR(alpha) in vitro, suggesting that this motif serves some function other than PPAR(alpha) binding in recruiting PPAR(alpha) to nuclear spots. CAP350 inhibited PPAR(alpha)-mediated transactivation in an LXXLL-dependent manner, suggesting that CAP350 represses PPAR(alpha) function. Our findings implicate CAP350 in a dynamic process that recruits PPAR(alpha) to discrete nuclear and cytoplasmic compartments and suggest that altered intracellular compartmentalization represents a regulatory process that modulates PPAR function.

The nuclear aryl hydocarbon receptor is involved in regulation of DNA repair and cell survival following treatment with ionizing radiation.

PubMed

Dittmann, K H; Rothmund, M C; Paasch, A; Mayer, C; Fehrenbacher, B; Schaller, M; Frauenstein, K; Fritsche, E; Haarmann-Stemmann, T; Braeuning, A; Rodemann, H P

2016-01-05

In the present study, we explored the role of the aryl hydrocarbon receptor (AhR) for γ-H2AX associated DNA repair in response to treatment with ionizing radiation. Ionizing radiation was able to stabilize AhR protein and to induce a nuclear translocation in a similar way as described for exposure to aromatic hydrocarbons. A comparable AhR protein stabilization was obtained by treatment with hydroxyl-nonenal-generated by radiation-induced lipid peroxidation. AhR knockdown resulted in significant radio-sensitization of both A549- and HaCaT cells. Under these conditions an increased amount of residual γ-H2AX foci and a delayed decline of γ-H2AX foci was observed. Knockdown of the co-activator ARNT, which is essential for transcriptional activation of AhR target genes, reduced AhR-dependent CYP1A expression in response to irradiation, but was without effect on the amount of residual γ-H2AX foci. Nuclear AhR was found in complex with γ-H2AX, DNA-PK, ATM and Lamin A. AhR and γ-H2AX form together nuclear foci, which disappear during DNA repair. Presence of nuclear AhR protein is associated with ATM activation and chromatin relaxation indicated by acetylation of histone H3. Taken together, we could show, that beyond the function as a transcription factor the nuclear AhR is involved in the regulation of DNA repair. Reduction of nuclear AhR inhibits DNA-double stand repair and radiosensitizes cells. First hints for its molecular mechanism suggest a role during ATM activation and chromatin relaxation, both essential for DNA repair. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Overview of DOE space nuclear propulsion programs

NASA Technical Reports Server (NTRS)

Newhouse, Alan R.

1993-01-01

An overview of Department of Energy space nuclear propulsion programs is presented in outline and graphic form. DOE's role in the development and safety assurance of space nuclear propulsion is addressed. Testing issues and facilities are discussed along with development needs and recent research activities.

The Lifecycle of Bayesian Network Models Developed for Multi-Source Signature Assessment of Nuclear Programs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gastelum, Zoe N.; White, Amanda M.; Whitney, Paul D.

2013-06-04

The Multi-Source Signatures for Nuclear Programs project, part of Pacific Northwest National Laboratory’s (PNNL) Signature Discovery Initiative, seeks to computationally capture expert assessment of multi-type information such as text, sensor output, imagery, or audio/video files, to assess nuclear activities through a series of Bayesian network (BN) models. These models incorporate knowledge from a diverse range of information sources in order to help assess a country’s nuclear activities. The models span engineering topic areas, state-level indicators, and facility-specific characteristics. To illustrate the development, calibration, and use of BN models for multi-source assessment, we present a model that predicts a country’s likelihoodmore » to participate in the international nuclear nonproliferation regime. We validate this model by examining the extent to which the model assists non-experts arrive at conclusions similar to those provided by nuclear proliferation experts. We also describe the PNNL-developed software used throughout the lifecycle of the Bayesian network model development.« less

Nuclear Receptor Coactivator Function in Reproductive Physiology and Behavior

PubMed Central

Molenda, Heather A.; Kilts, Caitlin P.; Allen, Rachel L.; Tetel, Marc J.

2009-01-01

Gonadal steroid hormones act throughout the body to elicit changes in gene expression that result in profound effects on reproductive physiology and behavior. Steroid hormones exert many of these effects by binding to their respective intracellular receptors, which are members of a nuclear receptor superfamily of transcriptional activators. A variety of in vitro studies indicate that nuclear receptor coactivators are required for efficient transcriptional activity of steroid receptors. Many of these coactivators are found in a variety of steroid hormone-responsive reproductive tissues, including the reproductive tract, mammary gland, and brain. While many nuclear receptor coactivators have been investigated in vitro, we are only now beginning to understand their function in reproductive physiology and behavior. In this review, we discuss the general mechanisms of action of nuclear receptor coactivators in steroid-dependent gene transcription. We then review some recent and exciting findings on the function of nuclear receptor coactivators in steroid-dependent brain development and reproductive physiology and behavior. PMID:12855594

U.S. Department of Energy Office of Nuclear Technology Research and Eevelopment ((NTRD) comprehensive summary of QA assessments for FY17

DOE Office of Scientific and Technical Information (OSTI.GOV)

Trost, Alan L.

The U.S. Department of Energy (DOE) Office of Nuclear Energy (NE) has developed a research and development (R&D) roadmap for its research, development, and demonstration (RD&D) activities to ensure nuclear energy remains a compelling and viable energy option for the U.S. The roadmap defines NE RD&D activities and objectives that address the challenges to research, develop and demonstrate options to the current U.S commercial fuel cycle to enable the safe, secure, economic, and sustainable expansion of nuclear energy, while minimizing proliferation and terrorism risks expanding the use of nuclear power. The roadmap enables the development of technologies and other solutionsmore » that can improve the reliability, sustain the safety, and extend the life of current reactors. In addition, it will help to develop improvements in the affordability of the new reactors to enable nuclear energy to help meet the Administration’s energy security and climate change goals.« less

Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters.

PubMed

Cremer, Marion; Schmid, Volker J; Kraus, Felix; Markaki, Yolanda; Hellmann, Ines; Maiser, Andreas; Leonhardt, Heinrich; John, Sam; Stamatoyannopoulos, John; Cremer, Thomas

2017-08-07

The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an 'open' local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC-INC) form two spatially co-aligned and functionally interacting networks. Using 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[-] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[-]) are enriched toward the compacted interior of CDCs (INC). Our results add further evidence in support of the ANC-INC network model. The different 3D topographies of DHS[+] and DHS[-] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an 'open,' active and 'closed,' inactive state.

Blockade of Y177 and Nuclear Translocation of Bcr-Abl Inhibits Proliferation and Promotes Apoptosis in Chronic Myeloid Leukemia Cells.

PubMed

Li, Qianyin; Huang, Zhenglan; Gao, Miao; Cao, Weixi; Xiao, Qin; Luo, Hongwei; Feng, Wenli

2017-03-02

The gradual emerging of resistance to imatinib urgently calls for the development of new therapy for chronic myeloid leukemia (CML). The fusion protein Bcr-Abl, which promotes the malignant transformation of CML cells, is mainly located in the cytoplasm, while the c-Abl protein which is expressed in the nucleus can induce apoptosis. Based on the hetero-dimerization of FKBP (the 12-kDa FK506- and rapamycin-binding protein) and FRB (the FKBP-rapamycin binding domain of the protein kinase, mTOR) mediated by AP21967, we constructed a nuclear transport system to induce cytoplasmic Bcr-Abl into nuclear. In this study, we reported the construction of the nuclear transport system, and we demonstrated that FN3R (three nuclear localization signals were fused to FRBT2098L with a FLAG tag), HF2S (two FKBP domains were in tandem and fused to the SH2 domain of Grb2 with an HA tag) and Bcr-Abl form a complexus upon AP21967. Bcr-Abl was imported into the nucleus successfully by the nuclear transport system. The nuclear transport system inhibited CML cell proliferation through mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 5 (STAT5) pathways mainly by HF2S. It was proven that nuclear located Bcr-Abl induced CML cell (including imatinib-resistant K562G01 cells) apoptosis by activation of p73 and its downstream molecules. In summary, our study provides a new targeted therapy for the CML patients even with Tyrosine Kinase Inhibitor (TKI)-resistance.

Nuclear scaffold attachment stimulates, but is not essential for ARS activity in Saccharomyces cerevisiae: analysis of the Drosophila ftz SAR.

PubMed Central

Amati, B; Pick, L; Laroche, T; Gasser, S M

1990-01-01

Nuclei isolated from eukaryotic cells can be depleted of histones and most soluble nuclear proteins to isolate a structural framework called the nuclear scaffold. This structure maintains specific interactions with genomic DNA at sites known as scaffold attached regions (SARs), which are thought to be the bases of DNA loops. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, genomic ARS elements are recovered as SARs. In addition, SARs from Drosophila melanogaster bind to yeast nuclear scaffolds in vitro and a subclass of these promotes autonomous replication of plasmids in yeast. In the present report, we present fine mapping studies of the Drosophila ftz SAR, which has both SAR and ARS activities in yeast. The data establish a close relationship between the sequences involved in ARS activity and scaffold binding: ARS elements that can bind the nuclear scaffold in vitro promote more efficient plasmid replication in vivo, but scaffold association is not a strict prerequisite for ARS function. Efficient interaction with nuclear scaffolds from both yeast and Drosophila requires a minimal length of SAR DNA that contains reiteration of a narrow minor groove structure of the double helix. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2123454

The TACIS Nuclear Programme: Assistance in Upgrading Russian Nuclear Power Stations - An Overview of the Individual Projects in the Internet

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bieth, Michel; Schoels, Hubert

2006-07-01

The European Union' TACIS1 programme has been established for the New Independent States (NIS), among them in the Russian Federation since 1991. One priority of TACIS funding is Nuclear Safety. The European Commission has made available a total of 944 Million Euros for nuclear safety programmes covering the period 1991-2003. The TACIS nuclear safety programme is devoted to the improvement of the safety of Soviet designed nuclear installations in providing technology and safety culture transfer. JRC is carrying out works in the following areas: On-Site Assistance for TACIS operating Nuclear Power Plants; Design Safety and Dissemination of TACIS results; Reactormore » Pressure Vessel Embrittlement for VVER; Regulatory Assistance; Industrial Waste Management; Nuclear Safeguards; All TACIS projects, dealing with these areas of activity are now available in so called Project Description Sheets (PDS) or Project Results Sheets (PRS) in the Internet for everybody. JRC has created in the Internet an easy to open and to browse database which contains the result of works in relation to the above mentioned nuclear activities. This presentation gives an on-line overview of the app. 430 projects which have been implemented so far since the outset of the TACIS Nuclear Programme in the Russian Federation, which is representative to the other CIS countries, benefiting from the TACIS. The presentation will mainly consist of an on-line-demonstration of the TACIS Nuclear WEB Page, created by JRC. (authors)« less

Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

PubMed Central

Ok, Chi Young; Tzankov, Alexandar; Manyam, Ganiraju C.; Sun, Ruifan; Visco, Carlo; Zhang, Mingzhi; Montes-Moreno, Santiago; Dybkaer, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W.L.; van Krieken, J. Han; Huh, Jooryung; Ponzoni, Maurilio; Ferreri, Andrés J.M.; Møller, Michael B.; Wang, Jinfeng; Parsons, Ben M.; Winter, Jane N.; Piris, Miguel A.; Pham, Lan V.; Medeiros, L. Jeffrey; Young, Ken H.

2015-01-01

Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications. PMID:26324762

Orientia tsutsugamushi uses two Ank effectors to modulate NF-κB p65 nuclear transport and inhibit NF-κB transcriptional activation.

PubMed

Evans, Sean M; Rodino, Kyle G; Adcox, Haley E; Carlyon, Jason A

2018-05-01

Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that threatens over one billion people. Nuclear translocation of the transcription factor, NF-κB, is the central initiating cellular event in the antimicrobial response. Here, we report that NF-κB p65 nuclear accumulation and NF-κB-dependent transcription are inhibited in O. tsutsugamushi infected HeLa cells and/or primary macrophages, even in the presence of TNFα. The bacterium modulates p65 subcellular localization by neither degrading it nor inhibiting IκBα degradation. Rather, it exploits host exportin 1 to mediate p65 nuclear export, as this phenomenon is leptomycin B-sensitive. O. tsutsugamushi antagonizes NF-κB-activated transcription even when exportin 1 is inhibited and NF-κB consequently remains in the nucleus. Two ankyrin repeat-containing effectors (Anks), Ank1 and Ank6, each of which possess a C-terminal F-box and exhibit 58.5% amino acid identity, are linked to the pathogen's ability to modulate NF-κB. When ectopically expressed, both translocate to the nucleus, abrogate NF-κB-activated transcription in an exportin 1-independent manner, and pronouncedly reduce TNFα-induced p65 nuclear levels by exportin 1-dependent means. Flag-tagged Ank 1 and Ank6 co-immunoprecipitate p65 and exportin 1. Both also bind importin β1, a host protein that is essential for the classical nuclear import pathway. Importazole, which blocks importin β1 activity, abrogates Ank1 and Ank6 nuclear translocation. The Ank1 and Ank6 regions that bind importin β1 also mediate their transport into the nucleus. Yet, these regions are distinct from those that bind p65/exportin 1. The Ank1 and Ank6 F-box and the region that lies between it and the ankyrin repeat domain are essential for blocking p65 nuclear accumulation. These data reveal a novel mechanism by which O. tsutsugamushi modulates the activity and nuclear transport of NF-κB p65 and identify the first microbial proteins that co-opt both importin β1 and exportin 1 to antagonize a critical arm of the antimicrobial response.

Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

PubMed

Grant, Frederick D; Gelfand, Michael J; Drubach, Laura A; Treves, S Ted; Fahey, Frederic H

2015-04-01

Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients were age 5 years or younger. For 12 commonly performed pediatric nuclear medicine studies, updated radiation dose estimates can guide efforts to reduce radiation exposure and provide current information for discussing radiation exposure and risk with referring physicians, patients and families. There can be substantial differences in radiation exposure for the same procedure, depending upon which of these two guidelines is followed. This discordance identifies opportunities for harmonization of the guidelines, which may lead to further reduction in nuclear medicine radiation doses in children.

Modeling meiotic chromosome pairing: nuclear envelope attachment, telomere-led active random motion, and anomalous diffusion

PubMed Central

Marshall, Wallace F.; Fung, Jennifer C.

2016-01-01

The recognition and pairing of homologous chromosomes during meiosis is a complex physical and molecular process involving a combination of polymer dynamics and molecular recognition events. Two highly conserved features of meiotic chromosome behavior are the attachment of telomeres to the nuclear envelope and the active random motion of telomeres driven by their interaction with cytoskeletal motor proteins. Both of these features have been proposed to facilitate the process of homolog pairing, but exactly what role these features play in meiosis remains poorly understood. Here we investigate the roles of active motion and nuclear envelope tethering using a Brownian dynamics simulation in which meiotic chromosomes are represented by a Rouse polymer model subjected to tethering and active forces at the telomeres. We find that tethering telomeres to the nuclear envelope slows down pairing relative to the rates achieved by un-attached chromosomes, but that randomly-directed active forces applied to the telomeres speeds up pairing dramatically in a manner that depends on the statistical properties of the telomere force fluctuations. The increased rate of initial pairing cannot be explained by stretching out of the chromosome conformation but instead seems to correlate with anomalous diffusion of sub-telomeric regions. PMID:27046097

Modeling meiotic chromosome pairing: nuclear envelope attachment, telomere-led active random motion, and anomalous diffusion

NASA Astrophysics Data System (ADS)

Marshall, Wallace F.; Fung, Jennifer C.

2016-04-01

The recognition and pairing of homologous chromosomes during meiosis is a complex physical and molecular process involving a combination of polymer dynamics and molecular recognition events. Two highly conserved features of meiotic chromosome behavior are the attachment of telomeres to the nuclear envelope and the active random motion of telomeres driven by their interaction with cytoskeletal motor proteins. Both of these features have been proposed to facilitate the process of homolog pairing, but exactly what role these features play in meiosis remains poorly understood. Here we investigate the roles of active motion and nuclear envelope tethering using a Brownian dynamics simulation in which meiotic chromosomes are represented by a Rouse polymer model subjected to tethering and active forces at the telomeres. We find that tethering telomeres to the nuclear envelope slows down pairing relative to the rates achieved by unattached chromosomes, but that randomly directed active forces applied to the telomeres speed up pairing dramatically in a manner that depends on the statistical properties of the telomere force fluctuations. The increased rate of initial pairing cannot be explained by stretching out of the chromosome conformation but instead seems to correlate with anomalous diffusion of sub-telomeric regions.

Platinum nanoparticles reduce ovariectomy-induced bone loss by decreasing osteoclastogenesis

PubMed Central

Kim, Woon-Ki; Kim, Jin-Chun; Park, Hyun-Jung; Sul, Ok-Joo; Lee, Mi-Hyun; Kim, Ji-Soon

2012-01-01

Platinum nanoparticles (PtNP) exhibit remarkable antioxidant activity. There is growing evidence concerning a positive relationship between oxidative stress and bone loss, suggesting that PtNP could protect against bone loss by modulating oxidative stress. Intragastric administration of PtNP reduced ovariectomy (OVX)-induced bone loss with a decreased level of activity and number of osteoclast (OC) in vivo. PtNP inhibited OC formation by impairing the receptor activator of nuclear factor-κB ligand (RANKL) signaling. This impairment was due to a decreased activation of nuclear factor-κB and a reduced level of nuclear factor in activated T-cells, cytoplasmic 1 (NFAT2). PtNP lowered RANKL-induced long lasting reactive oxygen species as well as intracellular concentrations of Ca2+ oscillation. Our data clearly highlight the potential of PtNP for the amelioration of bone loss after estrogen deficiency by attenuated OC formation. PMID:22525805

Shot BADGER, a test of the UPSHOT-KNOTHOLE Series, 18 April 1953. Technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Massie, J.; Maag, C.; Rohrer, S.

1982-01-12

This report describes the activities of DOD personnel in Shot BADGER, the sixth nuclear test in the UPSHOT-KNOTHOLE atmospheric nuclear weapons testing series. The test, conducted on 18 April 1953, involved military personnel in Exercise Desert Rock V, AFSWP, AFSWC, and AEC test activities. The largest activity was the 2d Marine Corps Provisional Atomic Exercise Brigade maneuver involving 2,167 Marines.

Identification of COUP-TFII Orphan Nuclear Receptor as a Retinoic Acid-Activated Receptor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kruse, Schoen W; Suino-Powell, Kelly; Zhou, X Edward

2010-01-12

The chicken ovalbumin upstream promoter-transcription factors (COUP-TFI and II) make up the most conserved subfamily of nuclear receptors that play key roles in angiogenesis, neuronal development, organogenesis, cell fate determination, and metabolic homeostasis. Although the biological functions of COUP-TFs have been studied extensively, little is known of their structural features or aspects of ligand regulation. Here we report the ligand-free 1.48 {angstrom} crystal structure of the human COUP-TFII ligand-binding domain. The structure reveals an autorepressed conformation of the receptor, where helix {alpha}10 is bent into the ligand-binding pocket and the activation function-2 helix is folded into the cofactor binding site,more » thus preventing the recruitment of coactivators. In contrast, in multiple cell lines, COUP-TFII exhibits constitutive transcriptional activity, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, and ligand binding, substantially reduce the COUP-TFII transcriptional activity. Importantly, retinoid acids are able to promote COUP-TFII to recruit coactivators and activate a COUP-TF reporter construct. Although the concentration needed is higher than the physiological levels of retinoic acids, these findings demonstrate that COUP-TFII is a ligand-regulated nuclear receptor, in which ligands activate the receptor by releasing it from the autorepressed conformation.« less

Hypericin-mediated sonodynamic therapy induces autophagy and decreases lipids in THP-1 macrophage by promoting ROS-dependent nuclear translocation of TFEB.

PubMed

Li, Xuesong; Zhang, Xin; Zheng, Longbin; Kou, Jiayuan; Zhong, Zhaoyu; Jiang, Yueqing; Wang, Wei; Dong, Zengxiang; Liu, Zhongni; Han, Xiaobo; Li, Jing; Tian, Ye; Zhao, Yajun; Yang, Liming

2016-12-22

Lipid catabolism disorder is the primary cause of atherosclerosis. Transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy to promote lipid degradation. Hypericin-mediated sonodynamic therapy (HY-SDT) has been proved non-invasively inducing THP-1-derived macrophage apoptosis; however, it is unknown whether macrophage autophagy could be triggered by HY-SDT to influence cellular lipid catabolism via regulating TFEB. Here, we report that HY-SDT resulted in the time-dependent THP-1-derived macrophage autophagy activation through AMPK/AKT/mTOR pathway. Besides, TFEB nuclear translocation in macrophage was triggered by HY-SDT to promote autophagy activation and lysosome regeneration which enhanced lipid degradation in response to atherogenic lipid stressors. Moreover, following HY-SDT, the ABCA1 expression level was increased to promote lipid efflux in macrophage, and the expression levels of CD36 and SR-A were decreased to inhibit lipid uptake, both of which were prevented by TFEB knockdown. These results indicated that TFEB nuclear translocation activated by HY-SDT was not only the key regulator of autophagy activation and lysosome regeneration in macrophage to promote lipolysis, but also had a crucial role in reverse cholesterol transporters to decrease lipid uptake and increase lipid efflux. Reactive oxygen species (ROS) were adequately generated in macrophage by HY-SDT. Further, ROS scavenger N-acetyl-l-cysteine abolished HY-SDT-induced TFEB nuclear translocation and autophagy activation, implying that ROS were the primary upstream factors responsible for these effects during HY-SDT. In summary, our data indicate that HY-SDT decreases lipid content in macrophage by promoting ROS-dependent nuclear translocation of TFEB to influence consequent autophagy activation and cholesterol transporters. Thus, HY-SDT may be beneficial for atherosclerosis via TFEB regulation to ameliorate lipid overload in atherosclerotic plaques.

An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death.

PubMed

Garcia-Belinchón, Mercè; Sánchez-Osuna, María; Martínez-Escardó, Laura; Granados-Colomina, Carla; Pascual-Guiral, Sònia; Iglesias-Guimarais, Victoria; Casanelles, Elisenda; Ribas, Judit; Yuste, Victor J

2015-08-21

Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as "apoptosis-necrosis continuum." To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

An Early and Robust Activation of Caspases Heads Cells for a Regulated Form of Necrotic-like Cell Death*

PubMed Central

Garcia-Belinchón, Mercè; Sánchez-Osuna, María; Martínez-Escardó, Laura; Granados-Colomina, Carla; Pascual-Guiral, Sònia; Iglesias-Guimarais, Victoria; Casanelles, Elisenda; Ribas, Judit; Yuste, Victor J.

2015-01-01

Apoptosis is triggered by the activation of caspases and characterized by chromatin condensation and nuclear fragmentation (type II nuclear morphology). Necrosis is depicted by a gain in cell volume (oncosis), swelling of organelles, plasma membrane leakage, and subsequent loss of intracellular contents. Although considered as different cell death entities, there is an overlap between apoptosis and necrosis. In this sense, mounting evidence suggests that both processes can be morphological expressions of a common biochemical network known as “apoptosis-necrosis continuum.” To gain insight into the events driving the apoptosis-necrosis continuum, apoptotically proficient cells were screened facing several apoptotic inducers for the absence of type II apoptotic nuclear morphologies. Chelerythrine was selected for further studies based on its cytotoxicity and the lack of apoptotic nuclear alterations. Chelerythrine triggered an early plasma membrane leakage without condensed chromatin aggregates. Ultrastructural analysis revealed that chelerythrine-mediated cytotoxicity was compatible with a necrotic-like type of cell death. Biochemically, chelerythrine induced the activation of caspases. Moreover, the inhibition of caspases prevented chelerythrine-triggered necrotic-like cell death. Compared with staurosporine, chelerythrine induced stronger caspase activation detectable at earlier times. After using a battery of chemicals, we found that high concentrations of thiolic antioxidants fully prevented chelerythrine-driven caspase activation and necrotic-like cell death. Lower amounts of thiolic antioxidants partially prevented chelerythrine-mediated cytotoxicity and allowed cells to display type II apoptotic nuclear morphology correlating with a delay in caspase-3 activation. Altogether, these data support that an early and pronounced activation of caspases can drive cells to undergo a form of necrotic-like regulated cell death. PMID:26124276

Nuclear hormone receptor coregulator: role in hormone action, metabolism, growth, and development.

PubMed

Mahajan, Muktar A; Samuels, Herbert H

2005-06-01

Nuclear hormone receptor coregulator (NRC) (also referred to as activating signal cointegrator-2, thyroid hormone receptor-binding protein, peroxisome proliferator activating receptor-interacting protein, and 250-kDa receptor associated protein) belongs to a growing class of nuclear cofactors widely known as coregulators or coactivators that are necessary for transcriptional activation of target genes. The NRC gene is also amplified and overexpressed in breast, colon, and lung cancers. NRC is a 2063-amino acid protein that harbors a potent N-terminal activation domain (AD1) and a second more centrally located activation domain (AD2) that is rich in Glu and Pro. Near AD2 is a receptor-interacting domain containing an LxxLL motif (LxxLL-1), which interacts with a wide variety of ligand-bound nuclear hormone receptors with high affinity. A second LxxLL motif (LxxLL-2) located in the C-terminal region of NRC is more restricted in its nuclear hormone receptor specificity. The intrinsic activation potential of NRC is regulated by a C-terminal serine, threonine, leucine-regulatory domain. The potential role of NRC as a cointegrator is suggested by its ability to enhance transcriptional activation of a wide variety of transcription factors and from its in vivo association with a number of known transcriptional regulators including CBP/p300. Recent studies in mice indicate that deletion of both NRC alleles leads to embryonic lethality resulting from general growth retardation coupled with developmental defects in the heart, liver, brain, and placenta. NRC(-/-) mouse embryo fibroblasts spontaneously undergo apoptosis, indicating the importance of NRC as a prosurvival and antiapoptotic gene. Studies with 129S6 NRC(+/-) mice indicate that NRC is a pleiotropic regulator that is involved in growth, development, reproduction, metabolism, and wound healing.

Emergency Support Function 15 Standard Operating Procedures

DTIC Science & Technology

2013-08-01

learned from numerous incidents to include the BP oil spill, the Fukushima nuclear incident, Hurricane Sandy and the Boston Marathon attack. Guidance is...Staffing  Operations  Activation  Incident Operations  Case Study - 2013 Boston Marathon Bombing  Case Study - 2011 Fukushima Nuclear Crisis...Quick Summary  Radiological Dispersal Device (RDD)  Improvised Nuclear Device (IND)  Federal Response  Case Studies – 2011 Fukushima Nuclear

Arachidonate 15-Lipoxygenase 2 as an Endogenous Inhibitor of Prostate Cancer Development

DTIC Science & Technology

2006-03-01

dehydrogenase; NHP, normal human prostate epithelial cells; PCa, prostate cancer; NLS, nuclear localization signal; PPAR -, peroxisome proliferator...cloned, i.e., 15-LOX2sv-a/b/c, are mostly excluded from the nucleus. A potential bi-partite nuclear localization signal (NLS...only partially involved in the nuclear import of 15-LOX2. To elucidate the relationship between nuclear localization , enzymatic activity, and tumor

Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver.

PubMed

Sadi, Gökhan; Bozan, Davut; Yildiz, Huseyin Bekir

2014-08-01

Resveratrol is a strong antioxidant that exhibits blood glucose-lowering effects, which might contribute to its usefulness in preventing complications associated with diabetes. The present study aimed to investigate resveratrol effects on catalase (CAT) and glutathione peroxidase (GPx) gene and protein expression, their phosphorylation states and activities in rat liver of STZ-induced diabetes. Diabetes increased the levels of total protein phosphorylation and p-CAT, while mRNA expression, protein levels, and activity were reduced. Although diabetes induced transcriptional repression over GPx, it did not affect the protein levels and activity. When resveratrol was administered to diabetic rats, an increase in activity was associated with an increase in p-GPx levels. Decrease in Sirtuin1 (SIRT1) and nuclear factor erythroid 2-related factor (Nrf2) and increase in nuclear factor kappa B (NFκB) gene expression in diabetes were associated with a decrease in CAT and GPx mRNA expression. A possible compensatory mechanism for reduced gene expression of antioxidant enzymes is proved to be nuclear translocation of redox-sensitive Nrf2 and NFκB in diabetes which is confirmed by the increase in nuclear and decrease in cytoplasmic protein levels of Nrf2 and NFκB. Taken together, these findings revealed that an increase in the oxidized state in diabetes intricately modified the cellular phosphorylation status and regulation of antioxidant enzymes. Gene regulation of antioxidant enzymes was accompanied by nuclear translocation of Nrf2 and NFκB. Resveratrol administration also activated a coordinated cytoprotective response against diabetes-induced changes in liver tissues.

Under the Nuclear Umbrella.

ERIC Educational Resources Information Center

Williams, Leon F.

1987-01-01

Entertains the thesis that social work has a stake in the technological-humanistic debate and should greet the recent and spectacular technological failures with protest and alarm. Discusses relationship of nuclear issue and social work, effects of nuclear issue on children, and Chernobyl. Advocates pacifism, activism, and a coherent conception of…

10 CFR 820.20 - Purpose and scope.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES Enforcement Process § 820.20 Purpose and scope... violations of the DOE Nuclear Safety Requirements, for determining, whether a violation has occurred, for... of a violation of: (1) Any DOE Nuclear Safety Requirement set forth in the Code of Federal...

10 CFR 820.20 - Purpose and scope.

Code of Federal Regulations, 2012 CFR

2012-01-01

... OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES Enforcement Process § 820.20 Purpose and scope... violations of the DOE Nuclear Safety Requirements, for determining, whether a violation has occurred, for... of a violation of: (1) Any DOE Nuclear Safety Requirement set forth in the Code of Federal...

10 CFR 820.20 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES Enforcement Process § 820.20 Purpose and scope... violations of the DOE Nuclear Safety Requirements, for determining, whether a violation has occurred, for... of a violation of: (1) Any DOE Nuclear Safety Requirement set forth in the Code of Federal...

10 CFR 820.20 - Purpose and scope.

Code of Federal Regulations, 2014 CFR

2014-01-01

... OF ENERGY PROCEDURAL RULES FOR DOE NUCLEAR ACTIVITIES Enforcement Process § 820.20 Purpose and scope... violations of the DOE Nuclear Safety Requirements, for determining, whether a violation has occurred, for... of a violation of: (1) Any DOE Nuclear Safety Requirement set forth in the Code of Federal...