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

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.

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.

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

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

Activation analysis study on Li-ion batteries for nuclear forensic applications

NASA Astrophysics Data System (ADS)

Johnson, Erik B.; Whitney, Chad; Holbert, Keith E.; Zhang, Taipeng; Stannard, Tyler; Christie, Anthony; Harper, Peter; Anderson, Blake; Christian, James F.

2015-06-01

The nuclear materials environment has been increasing significantly in complexity over the past couple of decades. The prevention of attacks from nuclear weapons is becoming more difficult, and nuclear forensics is a deterrent by providing detailed information on any type of nuclear event for proper attribution. One component of the nuclear forensic analysis is a measurement of the neutron spectrum. As an example, the neutron component provides information on the composition of the weapons, whether boosting is involved or the mechanisms used in creating a supercritical state. As 6Li has a large cross-section for thermal neutrons, the lithium battery is a primary candidate for assessing the neutron spectrum after detonation. The absorption process for 6Li yields tritium, which can be measured at a later point after the nuclear event, as long as the battery can be processed in a manner to successfully extract the tritium content. In addition, measuring the activated constituents after exposure provides a means to reconstruct the incident neutron spectrum. The battery consists of a spiral or folded layers of material that have unique, energy dependent interactions associated with the incident neutron flux. A detailed analysis on the batteries included a pre-irradiated mass spectrometry analysis to be used as input for neutron spectrum reconstruction. A set of batteries were exposed to a hard neutron spectrum delivered by the University of Massachusetts, Lowell research reactor Fast Neutron Irradiator (FNI). The gamma spectra were measured from the batteries within a few days and within a week after the exposure to obtain sufficient data on the activated materials in the batteries. The activity was calculated for a number of select isotopes, indicating the number of associated neutron interactions. The results from tritium extraction are marginal. A measurable increase in detected particles (gammas and betas) below 50 keV not self-attenuated by the battery was observed

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

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

Investigating The Nuclear Activity Of Barred Spirals: The case of NGC 1672

NASA Astrophysics Data System (ADS)

Jenkins, Leigh; Brandt, N.; Colbert, E.; Levan, A.; Roberts, T.; Ward, M.; Zezas, A.

2008-03-01

We present new results from Chandra and XMM-Newton X-ray observations of the nearby barred spiral galaxy NGC1672. It shows dramatic nuclear and extra-nuclear star formation activity, including starburst regions located either end of its prominent bar. Using new X-ray imaging and spectral information, together with supporting multiwavelength data, we show for the first time that NGC1672 possesses a faint, hard, central X-ray source surrounded by a circumnuclear starburst ring that dominates the X-ray emission in the region, presumably triggered and sustained by gas and dust driven inwards along the galactic bar. The faint central source may represent low-level AGN activity, or alternatively emission associated with star-formation in the nucleus. More generally, we present some preliminary results on a Chandra archival search for low-luminosity AGN activity in barred galaxies.

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

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.

Experimental Nuclear Physics Activity in Italy

NASA Astrophysics Data System (ADS)

Chiavassa, E.; de Marco, N.

2003-04-01

The experimental Nuclear Physics activity of the Italian researchers is briefly reviewed. The experiments, that are financially supported by the INFN, are done in strict collaboration by more than 500 INFN and University researchers. The experiments cover all the most important field of the modern Nuclear Physics with probes extremely different in energy and interactions. Researches are done in all the four National Laboratories of the INFN even if there is a deeper involvement of the two national laboratories expressly dedicated to Nuclear Physics: the LNL (Laboratorio Nazionale di Legnaro) and LNS (Laboratorio Nazionale del Sud) where nuclear spectroscopy and reaction dynamics are investigated. All the activities with electromagnetic probes develops in abroad laboratories as TJNAF, DESY, MAMI, ESFR and are dedicated to the studies of the spin physics and of the nucleon resonance; hypernuclear and kaon physics is investigated at LNF. A strong community of researchers work in the relativistic and ultra-relativistic heavy ions field in particular at CERN with the SPS Pb beam and in the construction of the ALICE detector for heavy-ion physics at the LHC collider. Experiments of astrophysical interest are done with ions of very low energy; in particular the LUNA accelerator facility at LNGS (Laboratorio Nazionale del Gran Sasso) succeeded measuring cross section at solar energies, below or near the solar Gamow peak. Interdisciplinary researches on anti-hydrogen atom spectroscopy and on measurements of neutron cross sections of interest for ADS development are also supported.

Active Nuclear Import of Membrane Proteins Revisited

PubMed Central

Laba, Justyna K.; Steen, Anton; Popken, Petra; Chernova, Alina; Poolman, Bert; Veenhoff, Liesbeth M.

2015-01-01

It is poorly understood how membrane proteins destined for the inner nuclear membrane pass the crowded environment of the Nuclear Pore Complex (NPC). For the Saccharomyces cerevisiae proteins Src1/Heh1 and Heh2, a transport mechanism was proposed where the transmembrane domains diffuse through the membrane while the extralumenal domains encoding a nuclear localization signal (NLS) and intrinsically disordered linker (L) are accompanied by transport factors and travel through the NPC. Here, we validate the proposed mechanism and explore and discuss alternative interpretations of the data. First, to disprove an interpretation where the membrane proteins become membrane embedded only after nuclear import, we present biochemical and localization data to support that the previously used, as well as newly designed reporter proteins are membrane-embedded irrespective of the presence of the sorting signals, the specific transmembrane domain (multipass or tail anchored), independent of GET, and also under conditions that the proteins are trapped in the NPC. Second, using the recently established size limit for passive diffusion of membrane proteins in yeast, and using an improved assay, we confirm active import of polytopic membrane protein with extralumenal soluble domains larger than those that can pass by diffusion on similar timescales. This reinforces that NLS-L dependent active transport is distinct from passive diffusion. Thirdly, we revisit the proposed route through the center of the NPC and conclude that the previously used trapping assay is, unfortunately, poorly suited to address the route through the NPC, and the route thus remains unresolved. Apart from the uncertainty about the route through the NPC, the data confirm active, transport factor dependent, nuclear transport of membrane-embedded mono- and polytopic membrane proteins in baker’s yeast. PMID:26473931

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)

Galaxy interactions and strength of nuclear activity

NASA Technical Reports Server (NTRS)

Simkin, S. M.

1990-01-01

Analysis of data in the literature for differential velocities and projected separations of nearby Seyfert galaxies with possible companions shows a clear difference in projected separations between type 1's and type 2's. This kinematic difference between the two activity classes reinforces other independent evidence that their different nuclear characteristics are related to a non-nuclear physical distinction between the two classes. The differential velocities and projected separations of the galaxy pairs in this sample yield mean galaxy masses, sizes, and mass to light ratios which are consistent with those found by the statistical methods of Karachentsev. Although the galaxy sample discussed here is too small and too poorly defined to provide robust support for these conclusions, the results strongly suggest that nuclear activity in Seyfert galaxies is associated with gravitational perturbations from companion galaxies, and that there are physical distinctions between the host companions of Seyfert 1 and Seyfert 2 nuclei which may depend both on the environment and the structure of the host galaxy itself.

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

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.

Nuclear removal during terminal lens fiber cell differentiation requires CDK1 activity: appropriating mitosis-related nuclear disassembly

PubMed Central

Chaffee, Blake R.; Shang, Fu; Chang, Min-Lee; Clement, Tracy M.; Eddy, Edward M.; Wagner, Brad D.; Nakahara, Masaki; Nagata, Shigekazu; Robinson, Michael L.; Taylor, Allen

2014-01-01

Lens epithelial cells and early lens fiber cells contain the typical complement of intracellular organelles. However, as lens fiber cells mature they must destroy their organelles, including nuclei, in a process that has remained enigmatic for over a century, but which is crucial for the formation of the organelle-free zone in the center of the lens that assures clarity and function to transmit light. Nuclear degradation in lens fiber cells requires the nuclease DNase IIβ (DLAD) but the mechanism by which DLAD gains access to nuclear DNA remains unknown. In eukaryotic cells, cyclin-dependent kinase 1 (CDK1), in combination with either activator cyclins A or B, stimulates mitotic entry, in part, by phosphorylating the nuclear lamin proteins leading to the disassembly of the nuclear lamina and subsequent nuclear envelope breakdown. Although most post-mitotic cells lack CDK1 and cyclins, lens fiber cells maintain these proteins. Here, we show that loss of CDK1 from the lens inhibited the phosphorylation of nuclear lamins A and C, prevented the entry of DLAD into the nucleus, and resulted in abnormal retention of nuclei. In the presence of CDK1, a single focus of the phosphonuclear mitotic apparatus is observed, but it is not focused in CDK1-deficient lenses. CDK1 deficiency inhibited mitosis, but did not prevent DNA replication, resulting in an overall reduction of lens epithelial cells, with the remaining cells possessing an abnormally large nucleus. These observations suggest that CDK1-dependent phosphorylations required for the initiation of nuclear membrane disassembly during mitosis are adapted for removal of nuclei during fiber cell differentiation. PMID:25139855

A new equation of state for core-collapse supernovae based on realistic nuclear forces and including a full nuclear ensemble

NASA Astrophysics Data System (ADS)

Furusawa, S.; Togashi, H.; Nagakura, H.; Sumiyoshi, K.; Yamada, S.; Suzuki, H.; Takano, M.

2017-09-01

We have constructed a nuclear equation of state (EOS) that includes a full nuclear ensemble for use in core-collapse supernova simulations. It is based on the EOS for uniform nuclear matter that two of the authors derived recently, applying a variational method to realistic two- and three-body nuclear forces. We have extended the liquid drop model of heavy nuclei, utilizing the mass formula that accounts for the dependences of bulk, surface, Coulomb and shell energies on density and/or temperature. As for light nuclei, we employ a quantum-theoretical mass evaluation, which incorporates the Pauli- and self-energy shifts. In addition to realistic nuclear forces, the inclusion of in-medium effects on the full ensemble of nuclei makes the new EOS one of the most realistic EOSs, which covers a wide range of density, temperature and proton fraction that supernova simulations normally encounter. We make comparisons with the FYSS EOS, which is based on the same formulation for the nuclear ensemble but adopts the relativistic mean field theory with the TM1 parameter set for uniform nuclear matter. The new EOS is softer than the FYSS EOS around and above nuclear saturation densities. We find that neutron-rich nuclei with small mass numbers are more abundant in the new EOS than in the FYSS EOS because of the larger saturation densities and smaller symmetry energy of nuclei in the former. We apply the two EOSs to 1D supernova simulations and find that the new EOS gives lower electron fractions and higher temperatures in the collapse phase owing to the smaller symmetry energy. As a result, the inner core has smaller masses for the new EOS. It is more compact, on the other hand, due to the softness of the new EOS and bounces at higher densities. It turns out that the shock wave generated by core bounce is a bit stronger initially in the simulation with the new EOS. The ensuing outward propagations of the shock wave in the outer core are very similar in the two simulations, which

Liver X receptor regulates hepatic nuclear O-GlcNAc signaling and carbohydrate responsive element-binding protein activity[S

PubMed Central

Bindesbøll, Christian; Fan, Qiong; Nørgaard, Rikke C.; MacPherson, Laura; Ruan, Hai-Bin; Wu, Jing; Pedersen, Thomas Å.; Steffensen, Knut R.; Yang, Xiaoyong; Matthews, Jason; Mandrup, Susanne; Nebb, Hilde I.; Grønning-Wang, Line M.

2015-01-01

Liver X receptor (LXR)α and LXRβ play key roles in hepatic de novo lipogenesis through their regulation of lipogenic genes, including sterol regulatory element-binding protein (SREBP)-1c and carbohydrate responsive element-binding protein (ChREBP). LXRs activate lipogenic gene transcription in response to feeding, which is believed to be mediated by insulin. We have previously shown that LXRs are targets for glucose-hexosamine-derived O-linked β-N-acetylglucosamine (O-GlcNAc) modification enhancing their ability to regulate SREBP-1c promoter activity in vitro. To elucidate insulin-independent effects of feeding on LXR-mediated lipogenic gene expression in vivo, we subjected control and streptozotocin-treated LXRα/β+/+ and LXRα/β−/− mice to a fasting-refeeding regime. We show that under hyperglycemic and hypoinsulinemic conditions, LXRs maintain their ability to upregulate the expression of glycolytic and lipogenic enzymes, including glucokinase (GK), SREBP-1c, ChREBPα, and the newly identified shorter isoform ChREBPβ. Furthermore, glucose-dependent increases in LXR/retinoid X receptor-regulated luciferase activity driven by the ChREBPα promoter was mediated, at least in part, by O-GlcNAc transferase (OGT) signaling in Huh7 cells. Moreover, we show that LXR and OGT interact and colocalize in the nucleus and that loss of LXRs profoundly reduced nuclear O-GlcNAc signaling and ChREBPα promoter binding activity in vivo. In summary, our study provides evidence that LXRs act as nutrient and glucose metabolic sensors upstream of ChREBP by modulating GK expression, nuclear O-GlcNAc signaling, and ChREBP expression and activity. PMID:25724563

The pathomechanism of cytochrome c oxidase deficiency includes nuclear DNA damage.

PubMed

Douiev, Liza; Saada, Ann

2018-06-07

Mitochondrial cytochrome c oxidase (COX, respiratory chain complex IV), contributes to ATP production via oxidative phosphorylation (OXPHOS). Clinical presentation of COX deficiency is heterogeneous ranging from mild to severe neuromuscular diseases. Anemia is among the symptoms and we have previously reported Fanconi anemia like features in COX4-1 deficiency, suggesting genomic instability and our preliminary results detected nuclear double stranded DNA breaks (DSB). We now quantified the DSB by phospho histone H2AX Ser139 staining of COX4-1 and COX6B1 deficient fibroblasts (225% and 215% of normal, respectively) and confirmed their occurrence by neutral comet assay. We further explored the mechanism of DNA damage by studying normal fibroblasts treated with micromolar concentrations of cyanide (KCN). Present results demonstrate elevated nuclear DSB in cells treated with 50 μM KCN for 24 h (170% of normal) in high-glucose medium conditions where ROS and ATP remain normal, although Glutathione content was partially decreased. In glucose-free and serum-free medium, where growth is hampered, DSB were not elevated. Additionally we demonstrate the benefit of nicotinamide riboside (NR) which ameliorated DSB in COX4-1, COX6B1 and KCN treated cells (130%, 154% and 87% of normal cells, respectively). Conversely a negative effect of a poly[ADP-ribose] polymerase (PARP) inhibitor was found. Although additional investigation is needed, our findings raise the possibility that the pathomechanism of COX deficiency and possibly also in other OXPHOS defects, include nuclear DNA damage resulting from nicotinamide adenine dinucleotide (NAD + ) deficit combined with a replicative state, rather than oxidative stress and energy depletion. Copyright © 2018 Elsevier B.V. All rights reserved.

NUA Activities at the Plant Nuclear Pore

PubMed Central

Xu, Xianfeng Morgan; Rose, Annkatrin

2007-01-01

NUA (Nuclear Pore Anchor), the Arabidopsis homolog of Tpr (Translocated Promoter Region), is one of the few nuclear pore proteins conserved between animals, yeast and plants. In the May issue of Plant Cell, we report that null mutants of NUA show a pleiotropic, early flowering phenotype accompanied by changes in SUMo and RNA homeostasis. We have shown that the early flowering phenotype is caused by changed abundances of flowering time regulators involved in several pathways. Arabidopsis nua mutants phenocopy mutants lacking the ESD4 (EARlY IN ShoRT DAYS 4) SUMo protease, similar to mutants of their respective yeast homologs. however, in contrast to the comparable yeast mutants, ESD4 does not appear to be delocalized from the nuclear pore in nua mutants. Taken together, our experimental data suggests a role for NUA in controlling mRNA export from the nucleus as well as SUMo protease activity at the nuclear pore, comparable but not identical to its homologs in other eukaryotes. Furthermore, characterization of NUA illustrates a potential link at the nuclear pore between SUMo modification, RNA homeostasis and plant developmental control. PMID:19704557

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

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…

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.

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 ...

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

p21 Activated kinase 1: Nuclear activity and its role during DNA damage repair.

PubMed

Pérez-Yépez, Eloy Andrés; Saldívar-Cerón, Héctor Iván; Villamar-Cruz, Olga; Pérez-Plasencia, Carlos; Arias-Romero, Luis Enrique

2018-05-01

p21-activated kinase 1 (PAK1) is a serine/threonine kinase activated by the small GTPases Rac1 and Cdc42. It is located in the chromosome 11q13 and is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme plays a pivotal role in the control of a number of fundamental cellular processes by phosphorylating its downstream substrates. In addition to its role in the cytoplasm, it is well documented that PAK1 also plays crucial roles in the nucleus participating in mitotic events and gene expression through its association and/or phosphorylation of several transcription factors, transcriptional co-regulators and cell cycle-related proteins, including Aurora kinase A (AURKA), polo-like kinase 1 (PLK1), the forkhead transcription factor (FKHR), estrogen receptor α (ERα), and Snail. More recently, PAK signaling has emerged as a component of the DNA damage response (DDR) as PAK1 activity influences the cellular sensitivity to ionizing radiation and promotes the expression of several genes involved in the Fanconi Anemia/BRCA pathway. This review will focus on the nuclear functions of PAK1 and its role in the regulation of DNA damage repair. Copyright © 2018 Elsevier B.V. All rights reserved.

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...

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.

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.

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...

Nuclear design of a very-low-activation fusion reactor

NASA Astrophysics Data System (ADS)

Cheng, E. T.; Hopkins, G. R.

1983-06-01

The nuclear design aspects of using very-low-activation materials, such as SiC, MgO, and aluminum for fusion-reactor first wall, blanket, and shield applications were investigated. In addition to the advantage of very-low radioactive inventory, it was found that the very-low-activation fusion reactor can also offer an adequate tritium-breeding ratio and substantial amount of blanket nuclear heating as a conventional-material-structured reactor does. The most-stringent design constraint found in a very-low-activation fusion reactor is the limited space available in the inboard region of a Tokamak concept for shielding to protect the superconducting toroidal field coil. A reference design was developed which mitigates the constraint by adopting a removable tungsten shield design that retains the inboard dimensions and gives the same shield performance as the reference STARFIRE Tokamak reactor design.

Uncertainty-driven nuclear data evaluation including thermal (n,α) applied to 59Ni

NASA Astrophysics Data System (ADS)

Helgesson, P.; Sjöstrand, H.; Rochman, D.

2017-11-01

This paper presents a novel approach to the evaluation of nuclear data (ND), combining experimental data for thermal cross sections with resonance parameters and nuclear reaction modeling. The method involves sampling of various uncertain parameters, in particular uncertain components in experimental setups, and provides extensive covariance information, including consistent cross-channel correlations over the whole energy spectrum. The method is developed for, and applied to, 59Ni, but may be used as a whole, or in part, for other nuclides. 59Ni is particularly interesting since a substantial amount of 59Ni is produced in thermal nuclear reactors by neutron capture in 58Ni and since it has a non-threshold (n,α) cross section. Therefore, 59Ni gives a very important contribution to the helium production in stainless steel in a thermal reactor. However, current evaluated ND libraries contain old information for 59Ni, without any uncertainty information. The work includes a study of thermal cross section experiments and a novel combination of this experimental information, giving the full multivariate distribution of the thermal cross sections. In particular, the thermal (n,α) cross section is found to be 12.7 ± . 7 b. This is consistent with, but yet different from, current established values. Further, the distribution of thermal cross sections is combined with reported resonance parameters, and with TENDL-2015 data, to provide full random ENDF files; all of this is done in a novel way, keeping uncertainties and correlations in mind. The random files are also condensed into one single ENDF file with covariance information, which is now part of a beta version of JEFF 3.3. Finally, the random ENDF files have been processed and used in an MCNP model to study the helium production in stainless steel. The increase in the (n,α) rate due to 59Ni compared to fresh stainless steel is found to be a factor of 5.2 at a certain time in the reactor vessel, with a relative

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,...

Nuclear Rocket Facility Decommissioning Project: Controlled Explosive Demolition of Neutron Activated Shield Wall

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

Michael R. Kruzic

2007-09-16

Located in Area 25 of the Nevada Test Site (NTS), the Test Cell A (TCA) Facility was used in the early to mid-1960s for the testing of nuclear rocket engines, as part of the Nuclear Rocket Development Program, to further space travel. Nuclear rocket testing resulted in the activation of materials around the reactors and the release of fission products and fuel particles in the immediate area. Identified as Corrective Action Unit 115, the TCA facility was decontaminated and decommissioned (D&D) from December 2004 to July 2005 using the Streamlined Approach for Environmental Restoration (SAFER) process, under the ''Federal Facilitymore » Agreement and Consent Order''. The SAFER process allows environmental remediation and facility closure activities (i.e., decommissioning) to occur simultaneously provided technical decisions are made by an experienced decision maker within the site conceptual site model, identified in the Data Quality Objective process. Facility closure involved a seven-step decommissioning strategy. Key lessons learned from the project included: (1) Targeted preliminary investigation activities provided a more solid technical approach, reduced surprises and scope creep, and made the working environment safer for the D&D worker. (2) Early identification of risks and uncertainties provided opportunities for risk management and mitigation planning to address challenges and unanticipated conditions. (3) Team reviews provided an excellent mechanism to consider all aspects of the task, integrated safety into activity performance, increase team unity and ''buy-in'' and promoted innovative and time saving ideas. (4) Development of CED protocols ensured safety and control. (5) The same proven D&D strategy is now being employed on the larger ''sister'' facility, Test Cell C.« less

Nuclear Mitochondrial DNA Activates Replication in Saccharomyces cerevisiae

PubMed Central

Chatre, Laurent; Ricchetti, Miria

2011-01-01

The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS) consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in. PMID:21408151

Nuclear mitochondrial DNA activates replication in Saccharomyces cerevisiae.

PubMed

Chatre, Laurent; Ricchetti, Miria

2011-03-08

The nuclear genome of eukaryotes is colonized by DNA fragments of mitochondrial origin, called NUMTs. These insertions have been associated with a variety of germ-line diseases in humans. The significance of this uptake of potentially dangerous sequences into the nuclear genome is unclear. Here we provide functional evidence that sequences of mitochondrial origin promote nuclear DNA replication in Saccharomyces cerevisiae. We show that NUMTs are rich in key autonomously replicating sequence (ARS) consensus motifs, whose mutation results in the reduction or loss of DNA replication activity. Furthermore, 2D-gel analysis of the mrc1 mutant exposed to hydroxyurea shows that several NUMTs function as late chromosomal origins. We also show that NUMTs located close to or within ARS provide key sequence elements for replication. Thus NUMTs can act as independent origins, when inserted in an appropriate genomic context or affect the efficiency of pre-existing origins. These findings show that migratory mitochondrial DNAs can impact on the replication of the nuclear region they are inserted in.

An Overview of the Nuclear Electric Xenon Ion System (NEXIS) Activity

NASA Technical Reports Server (NTRS)

Randolph, Thomas M.; Polk, James E., Jr.

2004-01-01

The Nuclear Electric Xenon Ion System (NEXIS) research and development activity within NASA's Project Prometheus, was one of three proposals selected by NASA to develop thruster technologies for long life, high power, high specific impulse nuclear electric propulsion systems that would enable more robust and ambitious science exploration missions to the outer solar system. NEXIS technology represents a dramatic improvement in the state-of-the-art for ion propulsion and is designed to achieve propellant throughput capabilities >= 2000 kg and efficiencies >= 78% while increasing the thruster power to >= 20 kW and specific impulse to >= 6000 s. The NEXIS technology uses erosion resistant carbon-carbon grids, a graphite keeper, a new reservoir hollow cathode, a 65-cm diameter chamber masked to produce a 57-cm diameter ion beam, and a shared neutralizer architecture to achieve these goals. The accomplishments of the NEXIS activity so far include performance testing of a laboratory model thruster, successful completion of a proof of concept reservoir cathode 2000 hour wear test, structural and thermal analysis of a completed development model thruster design, fabrication of most of the development model piece parts, and the nearly complete vacuum facility modifications to allow long duration wear testing of high power ion thrusters.

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.

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.

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

Nuclear Thermal Rocket Element Environmental Simulator (NTREES) Upgrade Activities

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.

2014-01-01

Over the past year the Nuclear Thermal Rocket Element Environmental Simulator (NTREES) has been undergoing a significant upgrade beyond its initial configuration. The NTREES facility is designed to perform realistic non-nuclear testing of nuclear thermal rocket (NTR) fuel elements and fuel materials. Although the NTREES facility cannot mimic the neutron and gamma environment of an operating NTR, it can simulate the thermal hydraulic environment within an NTR fuel element to provide critical information on material performance and compatibility. The first phase of the upgrade activities which was completed in 2012 in part consisted of an extensive modification to the hydrogen system to permit computer controlled operations outside the building through the use of pneumatically operated variable position valves. This setup also allows the hydrogen flow rate to be increased to over 200 g/sec and reduced the operation complexity of the system. The second stage of modifications to NTREES which has just been completed expands the capabilities of the facility significantly. In particular, the previous 50 kW induction power supply has been replaced with a 1.2 MW unit which should allow more prototypical fuel element temperatures to be reached. The water cooling system was also upgraded to so as to be capable of removing 100% of the heat generated during. This new setup required that the NTREES vessel be raised onto a platform along with most of its associated gas and vent lines. In this arrangement, the induction heater and water systems are now located underneath the platform. In this new configuration, the 1.2 MW NTREES induction heater will be capable of testing fuel elements and fuel materials in flowing hydrogen at pressures up to 1000 psi at temperatures up to and beyond 3000 K and at near-prototypic reactor channel power densities. NTREES is also capable of testing potential fuel elements with a variety of propellants, including hydrogen with additives to inhibit

THE AIMS AND ACTIVITIES OF THE INTERNATIONAL NETWORK OF NUCLEAR STRUCTURE AND DECAY DATA EVALUATORS.

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

NICHOLS,A.L.; TULI, J.K.

International Network of Nuclear Structure and Decay Data (NSDD) Evaluators consists of a number of evaluation groups and data service centers in several countries that appreciate the merits of working together to maintain and ensure the quality and comprehensive content of the ENSDF database (Evaluated Nuclear Structure Data File). Biennial meetings of the network are held under the auspices of the International Atomic Energy Agency (IAEA) to assign evaluation responsibilities, monitor progress, discuss improvements and emerging difficulties, and agree on actions to be undertaken by individual members. The evaluated data and bibliographic details are made available to users via variousmore » media, such as the journals ''Nuclear Physics A'' and ''Nuclear Data Sheets'', the World Wide Web, on CD-ROM, wall charts of the nuclides and ''Nuclear Wallet Cards''. While the ENSDF master database is maintained by the US National Nuclear Data Center at the Brookhaven National Laboratory, these data are also available from other nuclear data centers including the IAEA Nuclear Data Section. The Abdus Salam International Centre for Theoretical Physics (ICTP), Trieste, Italy, in cooperation with the IAEA, organizes workshops on NSDD at regular intervals. The primary aims of these particular workshops are to provide hands-on training in the data evaluation processes, and to encourage new evaluators to participate in NSDD activities. The technical contents of these NSDD workshops are described, along with the rationale for the inclusion of various topics.« less

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.

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.

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

The nuclear-factor kappaB pathway is activated in pterygium.

PubMed

Siak, Jay Jyh Kuen; Ng, See Liang; Seet, Li-Fong; Beuerman, Roger W; Tong, Louis

2011-01-05

Pterygium is a prevalent ocular surface disease with unknown pathogenesis. The authors investigated the role of nuclear factor kappa B (NF-κB) transcription factors in pterygium. Surgically excised primary pterygia were studied compared with uninvolved conjunctiva tissues. NF-κB activation was evaluated using Western blot analysis, ELISA, and DNA-binding assays. Primary pterygium fibroblasts were treated with TNF-α (20 ng/mL), and NF-κB activation was evaluated using immunocytochemistry, Western blot analysis, phospho-IκBα ELISA, and DNA-binding assays. TNF-α stimulation of NF-κB target genes RelB, NFKB2, RANTES, MCP-1, ENA-78, MMP-1, MMP-2, and MMP-3 in pterygium fibroblasts was compared with that in primary tenon fibroblasts by real-time PCR. Phosphorylation of IκBα (Ser32) was increased in pterygia tissues compared with uninvolved conjunctiva tissues, as determined by Western blot analysis and ELISA. IκBα expression was decreased, whereas nuclear RelA and p50 DNA-binding capacities were increased. Within 30 minutes of treatment with TNF-α, pterygium fibroblasts showed increased IκBα phosphorylation and nuclear translocation of RelA and p50. Treatment with TNF-α beyond 12 hours resulted in increased nuclear expression of RelB, p100, and p52. Furthermore, the upregulation of RANTES, MCP-1, ENA-78, MMP-1, MMP-2, and MMP-3 expression was more pronounced in TNF-α-treated pterygium fibroblasts than in tenon fibroblasts. The NF-κB pathway is shown for the first time to be activated in pterygia tissues compared with normal conjunctiva tissues. Stimulation by the inflammatory cytokine TNF-α can activate both canonical and noncanonical NF-κB pathways in pterygium fibroblasts with concomitant upregulation of NF-κB target genes.

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.

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

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.

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.

Nuclear Rocket Facility Decommissioning Project: Controlled Explosive Demolition of Neutron-Activated Shield Wall

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

Michael R. Kruzic

2008-06-01

Located in Area 25 of the Nevada Test Site (NTS), the Test Cell A (TCA) Facility (Figure 1) was used in the early to mid-1960s for testing of nuclear rocket engines, as part of the Nuclear Rocket Development Program, to further space travel. Nuclear rocket testing resulted in the activation of materials around the reactors and the release of fission products and fuel particles. The TCA facility, known as Corrective Action Unit 115, was decontaminated and decommissioned (D&D) from December 2004 to July 2005 using the Streamlined Approach for Environmental Restoration (SAFER) process, under the Federal Facility Agreement and Consentmore » Order. The SAFER process allows environmental remediation and facility closure activities (i.e., decommissioning) to occur simultaneously, provided technical decisions are made by an experienced decision maker within the site conceptual site model. Facility closure involved a seven-step decommissioning strategy. First, preliminary investigation activities were performed, including review of process knowledge documentation, targeted facility radiological and hazardous material surveys, concrete core drilling and analysis, shield wall radiological characterization, and discrete sampling, which proved to be very useful and cost-effective in subsequent decommissioning planning and execution and worker safety. Second, site setup and mobilization of equipment and personnel were completed. Third, early removal of hazardous materials, including asbestos, lead, cadmium, and oil, was performed ensuring worker safety during more invasive demolition activities. Process piping was to be verified void of contents. Electrical systems were de-energized and other systems were rendered free of residual energy. Fourth, areas of high radiological contamination were decontaminated using multiple methods. Contamination levels varied across the facility. Fixed beta/gamma contamination levels ranged up to 2 million disintegrations per minute (dpm)/100

The link between tidal interaction and nuclear activity in galaxies

NASA Technical Reports Server (NTRS)

Lin, D. N. C.; Pringle, J. E.; Rees, M. J.

1988-01-01

It is considered how nuclear activity in galaxies may be induced by the tidal perturbation of companion galaxies. It is suggested that if the central regions of the galaxies contain marginally self-gravitating disks of gas, trailing spiral density waves, triggered by nonaxisymmetric gravitational instability, lead to efficient angular momentum transport. If the net effect of the external perturbation is to increase the effect of self-gravity in the gas, then the result is to induce a considerable increase in the mass accretion rate into the central region on a relatively short time scale. With a simple prescription, the evolution of self-gravitating accretion disks is examined in this context. These results are discussed in the context of the frequent occurrence of nuclear activity in interacting galaxies.

Macroenvironmental factors including GDP per capita and physical activity in Europe.

PubMed

Cameron, Adrian J; Van Stralen, Maartje M; Kunst, Anton E; Te Velde, Saskia J; Van Lenthe, Frank J; Salmon, Jo; Brug, Johannes

2013-02-01

Socioeconomic inequalities in physical activity at the individual level are well reported. Whether inequalities in economic development and other macroenvironmental variables between countries are also related to physical activity at the country level is comparatively unstudied. We examined the relationship between country-level data on macroenvironmental factors (gross domestic product (GDP) per capita, public sector expenditure on health, percentage living in urban areas, and cars per 1000 population) with country-level physical activity prevalence obtained from previous pan-European studies. Studies that assessed leisuretime physical activity (n = 3 studies including 27 countries in adults, n = 2 studies including 28 countries in children) and total physical activity (n = 3 studies in adults including 16 countries) were analyzed separately as were studies among adults and children. Strong and consistent positive correlations were observed between country prevalence of leisure-time physical activity and country GDP per capita in adults (average r = 0.70; all studies, P G 0.05). In multivariate analysis, country prevalence of leisure-time physical activity among adults remained associated with country GDP per capita (two of three studies) but not urbanization or educational attainment. Among school-age populations, no association was found between country GDP per capita and country prevalence of leisure-time physical activity. In those studies that assessed total physical activity (which also includes occupational and transport physical activity), no association with country GDP per capita was observed. Clear differences in national leisure-time physical activity levels throughout Europe may be a consequence of economic development. Lack of economic development of some countries in Europe may make increasing leisure-time physical activity more difficult. Further examination of the link between country GDP per capita and national physical activity levels (across

Phosphorylated Nuclear Receptor CAR Forms a Homodimer To Repress Its Constitutive Activity for Ligand Activation

PubMed Central

Shizu, Ryota; Osabe, Makoto; Perera, Lalith; Moore, Rick; Sueyoshi, Tatsuya

2017-01-01

ABSTRACT The nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and the development of diseases, including diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase 2A (PP2A) dephosphorylates threonine 38 to activate CAR. Here we demonstrate that CAR undergoes homodimer-monomer conversion to regulate this dephosphorylation. By coexpression of two differently tagged CAR proteins in Huh-7 cells, mouse primary hepatocytes, and mouse livers, coimmunoprecipitation and two-dimensional gel electrophoresis revealed that CAR can form a homodimer in a configuration in which the PP2A/RACK1 binding site is buried within its dimer interface. Epidermal growth factor (EGF) was found to stimulate CAR homodimerization, thus constraining CAR in its inactive form. The agonistic ligand CITCO binds directly to the CAR homodimer and dissociates phosphorylated CAR into its monomers, exposing the PP2A/RACK1 binding site for dephosphorylation. Phenobarbital, which is not a CAR ligand, binds the EGF receptor, reversing the EGF signal to monomerize CAR for its indirect activation. Thus, the homodimer-monomer conversion is the underlying molecular mechanism that regulates CAR activation, by placing phosphorylated threonine 38 as the common target for both direct and indirect activation of CAR. PMID:28265001

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

Mobile robotics application in the nuclear industry

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

Jones, S.L.; White, J.R.

1995-03-01

Mobile robots have been developed to perform hazardous operations in place of human workers. Applications include nuclear plant inspection/maintenance, decontamination and decommissioning police/military explosive ordinance disposal (EOD), hostage/terrorist negotiations and fire fighting. Nuclear facilities have proven that robotic applications can be cost-effective solutions to reducing personnel exposure and plant downtime. The first applications of mobile robots in the nuclear industry began in the early 1980`s, with the first vehicles being one of a kind machines or adaptations of commercial EOD robots. These activities included efforts by numerous commercial companies, the U.S. Nuclear Regulatory Commission, EPRI, and several national laboratories. Somemore » of these efforts were driven by the recovery and cleanup activities at TMI which demonstrated the potential and need for a remote means of performing surveillance and maintenance tasks in nuclear plants. The use of these machines is now becoming commonplace in nuclear facilities throughout the world. The hardware maturity and the confidence of the users has progressed to the point where the applications of mobile robots is not longer considered a novelty. These machines are being used in applications where the result is to help achieve more aggressive goals for personnel radiation exposure and plant availability, perform tasks more efficiently, and allow plant operators to retrieve information from areas previously considered inaccessible. Typical examples include surveillance in high radiation areas (during operation and outage activities), radiation surveys, waste handling, and decontamination evolutions. This paper will discuss this evolution including specific applications experiences, examples of currently available technology, and the benefits derived from the use of mobile robotic vehicles in commercial nuclear power facilities.« less

Induced starburst and nuclear activity: Faith, facts, and theory

NASA Technical Reports Server (NTRS)

Shlosman, Isaac

1990-01-01

The problem of the origin of starburst and nuclear (nonstellar) activity in galaxies is reviewed. A physical understanding of the mechanism(s) that induce both types of activity requires one to address the following issues: (1) what is the source of fuel that powers starbursts and active galactic nuclei; and (2) how is it channeled towards the central regions of host galaxies? As a possible clue, the author examines the role of non-axisymmetric perturbations of galactic disks and analyzes their potential triggers. Global gravitational instabilities in the gas on scales approx. 100 pc appear to be crucial for fueling the active galactic nuclei.

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.

Active interrogation using low-energy nuclear reactions

NASA Astrophysics Data System (ADS)

Antolak, Arlyn; Doyle, Barney; Leung, Ka-Ngo; Morse, Daniel; Provencio, Paula

2005-09-01

High-energy photons and neutrons can be used to interrogate for heavily shielded fissile materials inside sealed cargo containers by detecting their prompt and/or delayed fission signatures. The FIND (Fissmat Inspection for Nuclear Detection) active interrogation system is based on a dual neutron+gamma source that uses low-energy (< 500 keV) proton- or deuteron-induced nuclear reactions to produce high intensities of mono-energetic gamma rays and/or neutrons. The source can be operated in either pulsed (e.g., to detect delayed photofission neutrons and gammas) or continuous (e.g., detecting prompt fission signatures) modes. For the gamma-rays, the source target can be segmented to incorporate different (p,γ) isotopes for producing gamma-rays at selective energies, thereby improving the probability of detection. The design parameters for the FIND system are discussed and preliminary accelerator-based measurements of gamma and neutron yields, background levels, and fission signals for several target materials under consideration are presented.

Multidirectional Efficacy of Biologically Active Nitro Compounds Included in Medicines.

PubMed

Olender, Dorota; Żwawiak, Justyna; Zaprutko, Lucjusz

2018-05-29

The current concept in searching for new bioactive products, including mainly original active substances with potential application in pharmacy and medicine, is based on compounds with a previously determined structure, well-known properties, and biological activity profile. Nowadays, many commonly used drugs originated from natural sources. Moreover, some natural materials have become the source of leading structures for processing further chemical modifications. Many organic compounds with great therapeutic significance have the nitro group in their structure. Very often, nitro compounds are active substances in many well-known preparations belonging to different groups of medicines that are classified according to their pharmacological potencies. Moreover, the nitro group is part of the chemical structure of veterinary drugs. In this review, we describe many bioactive substances with the nitro group, divided into ten categories, including substances with exciting activity and that are currently undergoing clinical trials.

Role of YAP activation in nuclear receptor CAR-mediated proliferation of mouse hepatocytes.

PubMed

Abe, Taiki; Amaike, Yuto; Shizu, Ryota; Takahashi, Miki; Kano, Makoto; Hosaka, Takuomi; Sasaki, Takamitsu; Kodama, Susumu; Matsuzawa, Atsushi; Yoshinari, Kouichi

2018-06-08

Constitutive androstane receptor (CAR) is a xenobiotic-responsive nuclear receptor that is highly expressed in the liver. CAR activation induces hepatocyte proliferation and hepatocarcinogenesis in rodents, but the mechanisms remain unclear. In this study, we investigated the association of CAR-dependent cell proliferation with Yes-associated protein (YAP), which is a transcriptional cofactor controlling organ size and cell growth through the interaction with various transcriptional factors including TEAD. In mouse livers, TCPOBOP (a mouse CAR activator) treatment increased the nuclear YAP accumulation and mRNA levels of YAP target genes as well as cell-cycle related genes along with liver hypertrophy and verteporfin (an inhibitor of YAP/TEAD interaction) cotreatment tended to attenuate them. Furthermore, in cell-based reporter gene assays, CAR activation enhanced the YAP/TEAD-dependent transcription. To investigate the role of YAP/TEAD activation in the CAR-dependent hepatocyte proliferation, we sought to establish an in vitro system completely reproducing CAR-dependent cell proliferation. Since CAR was only slightly expressed in cultured mouse primary hepatocytes compared to mouse livers and no proliferation was observed after treatment with TCPOBOP, we overexpressed CAR using mouse CAR expressing adenovirus (Ad-mCAR-V5) in mouse primary hepatocytes. Ad-mCAR-V5 infection and TCPOBOP treatment induced hepatocyte proliferation. Similar results were obtained with immortalized normal mouse hepatocytes as well. In the established in vitro system, CAR-dependent proliferation was strongly inhibited by Yap knockdown and completely abolished by verteporfin treatment. Our present results obtained in in vivo and in vitro experiments suggest that YAP/TEAD activation plays key roles in CAR-dependent proliferation of murine hepatocytes.

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

Nuclear Science References Database

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

Pritychenko, B., E-mail: pritychenko@bnl.gov; Běták, E.; Singh, B.

2014-06-15

The Nuclear Science References (NSR) database together with its associated Web interface, is the world's only comprehensive source of easily accessible low- and intermediate-energy nuclear physics bibliographic information for more than 210,000 articles since the beginning of nuclear science. The weekly-updated NSR database provides essential support for nuclear data evaluation, compilation and research activities. The principles of the database and Web application development and maintenance are described. Examples of nuclear structure, reaction and decay applications are specifically included. The complete NSR database is freely available at the websites of the National Nuclear Data Center (http://www.nndc.bnl.gov/nsr) and the International Atomic Energymore » Agency (http://www-nds.iaea.org/nsr)« less

Molecular hydrogen: An abundant energy source for bacterial activity in nuclear waste repositories

NASA Astrophysics Data System (ADS)

Libert, M.; Bildstein, O.; Esnault, L.; Jullien, M.; Sellier, R.

A thorough understanding of the energy sources used by microbial systems in the deep terrestrial subsurface is essential since the extreme conditions for life in deep biospheres may serve as a model for possible life in a nuclear waste repository. In this respect, H 2 is known as one of the most energetic substrates for deep terrestrial subsurface environments. This hydrogen is produced from abiotic and biotic processes but its concentration in natural systems is usually maintained at very low levels due to hydrogen-consuming bacteria. A significant amount of H 2 gas will be produced within deep nuclear waste repositories, essentially from the corrosion of metallic components. This will consequently improve the conditions for microbial activity in this specific environment. This paper discusses different study cases with experimental results to illustrate the fact that microorganisms are able to use hydrogen for redox processes (reduction of O 2, NO3-, Fe III) in several waste disposal conditions. Consequences of microbial activity include: alteration of groundwater chemistry and shift in geochemical equilibria, gas production or consumption, biocorrosion, and potential modifications of confinement properties. In order to quantify the impact of hydrogen bacteria, the next step will be to determine the kinetic rate of the reactions in realistic conditions.

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

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

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

Annual report to Congress. Department of Energy activities relating to the Defense Nuclear Facilities Safety Board, calendar year 2000

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

None

2001-03-01

This Annual Report to the Congress describes the Department of Energy's activities in response to formal recommendations and other interactions with the Defense Nuclear Facilities Safety Board. During 2000, the Department completed its implementation and proposed closure of one Board recommendation and completed all implementation plan milestones associated with two additional Board recommendations. Also in 2000, the Department formally accepted two new Board recommendations and developed implementation plans in response to those recommendations. The Department also made significant progress with a number of broad-based safety initiatives. These include initial implementation of integrated safety management at field sites and within headquartersmore » program offices, issuance of a nuclear safety rule, and continued progress on stabilizing excess nuclear materials to achieve significant risk reduction.« less

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

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

Nuclear receptors and nonalcoholic fatty liver disease1

PubMed Central

Cave, Matthew C.; Clair, Heather B.; Hardesty, Josiah E.; Falkner, K. Cameron; Feng, Wenke; Clark, Barbara J.; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A.; McClain, Craig J.; Prough, Russell A.

2016-01-01

Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

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.

Activation of postnatal neural stem cells requires nuclear receptor TLX.

PubMed

Niu, Wenze; Zou, Yuhua; Shen, Chengcheng; Zhang, Chun-Li

2011-09-28

Neural stem cells (NSCs) continually produce new neurons in postnatal brains. However, the majority of these cells stay in a nondividing, inactive state. The molecular mechanism that is required for these cells to enter proliferation still remains largely unknown. Here, we show that nuclear receptor TLX (NR2E1) controls the activation status of postnatal NSCs in mice. Lineage tracing indicates that TLX-expressing cells give rise to both activated and inactive postnatal NSCs. Surprisingly, loss of TLX function does not result in spontaneous glial differentiation, but rather leads to a precipitous age-dependent increase of inactive cells with marker expression and radial morphology for NSCs. These inactive cells are mispositioned throughout the granular cell layer of the dentate gyrus during development and can proliferate again after reintroduction of ectopic TLX. RNA-seq analysis of sorted NSCs revealed a TLX-dependent global expression signature, which includes the p53 signaling pathway. TLX regulates p21 expression in a p53-dependent manner, and acute removal of p53 can rescue the proliferation defect of TLX-null NSCs in culture. Together, these findings suggest that TLX acts as an essential regulator that ensures the proliferative ability of postnatal NSCs by controlling their activation through genetic interaction with p53 and other signaling pathways.

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

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

Controlling Nuclear Jaks and Stats for Specific Gene Activation by Ifn γ and Other Cytokines: A Possible Steroid-like Connection

PubMed Central

Johnson, Howard M.; Noon-Song, Ezra; Ahmed, Chulbul M.

2011-01-01

The mechanism of specific gene activation by cytokines that use JAK/STAT signalling pathway is unknown. There are four different types of JAKs and seven different types of STATs. In the classical model of signaling, ligand interacts solely with the receptor extracellular domain, which triggers JAK activation at the receptor cytoplasmic domain. Activated STATs are then said to carry out nuclear events of specific gene activation, including associated epigenetic changes that cause heterochromatin destabilization. Ligand, receptor, and JAKs play no further role in the classical model. Given the limited number of STATs and the activation of the same STATs by cytokines with different functions, the mechanism of the specificity of their signalling is not obvious. Focusing on gamma interferon (IFNγ), we have shown that ligand, receptor, and activated JAKs are involved in nuclear events that are associated with specific gene activation. In this model, receptor subunit IFNGR1 functions as a transcription/cotranscription factor and the JAKs are involved in key epigenetic events that are required for specific gene activation. The model has implications for gene activation in cancer as well as stem cell differentiation. PMID:22924155

Controlling Nuclear Jaks and Stats for Specific Gene Activation by Ifn γ and Other Cytokines: A Possible Steroid-like Connection.

PubMed

Johnson, Howard M; Noon-Song, Ezra; Ahmed, Chulbul M

2011-09-03

The mechanism of specific gene activation by cytokines that use JAK/STAT signalling pathway is unknown. There are four different types of JAKs and seven different types of STATs. In the classical model of signaling, ligand interacts solely with the receptor extracellular domain, which triggers JAK activation at the receptor cytoplasmic domain. Activated STATs are then said to carry out nuclear events of specific gene activation, including associated epigenetic changes that cause heterochromatin destabilization. Ligand, receptor, and JAKs play no further role in the classical model. Given the limited number of STATs and the activation of the same STATs by cytokines with different functions, the mechanism of the specificity of their signalling is not obvious. Focusing on gamma interferon (IFNγ), we have shown that ligand, receptor, and activated JAKs are involved in nuclear events that are associated with specific gene activation. In this model, receptor subunit IFNGR1 functions as a transcription/cotranscription factor and the JAKs are involved in key epigenetic events that are required for specific gene activation. The model has implications for gene activation in cancer as well as stem cell differentiation.

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.

Annual report to Congress: Department of Energy activities relating to the Defense Nuclear Facilities Safety Board, Calendar Year 1999

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

None

2000-02-01

This is the tenth Annual Report to the Congress describing Department of Energy activities in response to formal recommendations and other interactions with the Defense Nuclear Facilities Safety Board (Board). The Board, an independent executive-branch agency established in 1988, provides advice and recommendations to the Secretary of Energy regarding public health and safety issues at the Department's defense nuclear facilities. The Board also reviews and evaluates the content and implementation of health and safety standards, as well as other requirements, relating to the design, construction, operation, and decommissioning of the Department's defense nuclear facilities. During 1999, Departmental activities resulted inmore » the closure of nine Board recommendations. In addition, the Department has completed all implementation plan milestones associated with three Board recommendations. One new Board recommendation was received and accepted by the Department in 1999, and a new implementation plan is being developed to address this recommendation. The Department has also made significant progress with a number of broad-based initiatives to improve safety. These include expanded implementation of integrated safety management at field sites, opening of a repository for long-term storage of transuranic wastes, and continued progress on stabilizing excess nuclear materials to achieve significant risk reduction.« less

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.

Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

PubMed

Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

2005-04-01

Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P < 0.001), Smad4 (P = 0.002), and kangai 1 (P < 0.001) expression. An in vitro study showed that NF-kappaB activity in gastric cancer cells is controlled by and controls Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

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

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

Loss of Drosophila A-type lamin C initially causes tendon abnormality including disintegration of cytoskeleton and nuclear lamina in muscular defects.

PubMed

Uchino, Ryo; Nonaka, Yu-Ki; Horigome, Tuneyoshi; Sugiyama, Shin; Furukawa, Kazuhiro

2013-01-01

Lamins are the major components of nuclear envelope architecture, being required for both the structural and informational roles of the nuclei. Mutations of lamins cause a spectrum of diseases in humans, including muscular dystrophy. We report here that the loss of the A-type lamin gene, lamin C in Drosophila resulted in pupal metamorphic lethality caused by tendon defects, matching the characteristics of human A-type lamin revealed by Emery-Dreifuss muscular dystrophy (EDMD). In tendon cells lacking lamin C activity, overall cell morphology was affected and organization of the spectraplakin family cytoskeletal protein Shortstop which is prominently expressed in tendon cells gradually disintegrated, notably around the nucleus and in a manner correlating well with the degradation of musculature. Furthermore, lamin C null mutants were efficiently rescued by restoring lamin C expression to shortstop-expressing cells, which include tendon cells but exclude skeletal muscle cells. Thus the critical function of A-type lamin C proteins in Drosophila musculature is to maintain proper function and morphology of tendon cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Applications of neutron activation analysis in determination of natural and man-made radionuclides, including PA-231

NASA Astrophysics Data System (ADS)

Byrne, A. R.; Benedik, L.

1999-01-01

Neutron activation analysis (NAA), being essentially an isotopic and not an elemental method of analysis, is capable of determining a number of important radionuclides of radioecological interest by transformation into another, more easily quantifiable radionuclide. The nuclear characteristics which favour this technique may be summarized in an advantage factor relative to radiometric analysis of the original radioanalyte. Well known or hardly known examples include235U,238U,232Th,230Th,129I,99Tc,237Np and231Pa; a number of these are discussed and illustrated in analysis of real samples of environmental and biological origin. In particular, determination of231Pa by RNAA was performed using both postirradiation and preseparation methods. Application of INAA to enable the use of238U and232Th as endogenous (internal) radiotracers in alpha spectrometric analyses of uranium and thorium radioisotopes in radioecological studies is described, also allowing independent data sets to be obtained for quality control.

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

Nuclear Physics Activities in Asia and ANPhA

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

Sakai, H.

2011-05-06

On 18 July 2009 the Asian Nuclear Physics Association (ANPhA) has been officially launched in Beijing by the representatives from China, Korea, Japan and Vietnam. Since then Australia, India, Mongolia and Taiwan have joined to ANPhA and now the member country/region has increased to eight. Some activities and features on ANPhA are introduced. In addition, pleasant collaboration with Professor Arima by the author in regard to the Gamow-Teller quenching problem is also briefly mentioned.

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.

Role of osteoprotegerin/receptor activator of nuclear factor kappa B/receptor activator of nuclear factor kappa B ligand axis in nonalcoholic fatty liver disease.

PubMed

Pacifico, Lucia; Andreoli, Gian Marco; D'Avanzo, Miriam; De Mitri, Delia; Pierimarchi, Pasquale

2018-05-21

Concomitantly with the increase in the prevalences of overweight/obesity, nonalcoholic fatty liver disease (NAFLD) has worldwide become the main cause of chronic liver disease in both adults and children. Patients with fatty liver display features of metabolic syndrome (MetS), like insulin resistance (IR), glucose intolerance, hypertension and dyslipidemia. Recently, epidemiological studies have linked obesity, MetS, and NAFLD to decreased bone mineral density and osteoporosis, highlighting an intricate interplay among bone, adipose tissue, and liver. Osteoprotegerin (OPG), an important symbol of the receptor activator of nuclear factor-B ligand/receptor activator of nuclear factor kappa B/OPG system activation, typically considered for its role in bone metabolism, may also play critical roles in the initiation and perpetuation of obesity-related comorbidities. Clinical data have indicated that OPG concentrations are associated with hypertension, left ventricular hypertrophy, vascular calcification, endothelial dysfunction, and severity of liver damage in chronic hepatitis C. Nonetheless, the relationship between circulating OPG and IR as a key feature of MetS as well as between OPG and NAFLD remains uncertain. Thus, the aims of the present review are to provide the existent knowledge on these associations and to discuss briefly the underlying mechanisms linking OPG and NAFLD.

Activation of Postnatal Neural Stem Cells Requires Nuclear Receptor TLX

PubMed Central

Niu, Wenze; Zou, Yuhua; Shen, ChengCheng; Zhang, Chun-Li

2011-01-01

Neural stem cells (NSCs) continually produce new neurons in postnatal brains. However, the majority of these cells stay in a non-dividing, inactive state. The molecular mechanism that is required for these cells to enter proliferation still remains largely unknown. Here, we show that nuclear receptor TLX (NR2E1) controls the activation status of postnatal NSCs in mice. Lineage tracing indicates that TLX-expressing cells give rise to both activated and inactive postnatal NSCs. Surprisingly, loss of TLX function does not result in spontaneous glial differentiation, but rather leads to a precipitous age-dependent increase of inactive cells with marker expression and radial morphology for NSCs. These inactive cells are mis-positioned throughout the granular cell layer of the dentate gyrus during development and can proliferate again after reintroducing ectopic TLX. RNA-seq analysis of sorted NSCs revealed a TLX-dependent global expression signature, which includes the p53 signaling pathway. TLX regulates p21 expression in a p53-dependent manner and acute removal of p53 can rescue the proliferation defect of TLX-null NSCs in culture. Together, these findings suggest that TLX acts as an essential regulator that ensures the proliferative ability of postnatal NSCs by controlling their activation through genetic interaction with p53 and other signaling pathways. PMID:21957244

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.

Investigating the Nuclear Activity of Barred Spiral Galaxies: The Case of NGC 1672

NASA Astrophysics Data System (ADS)

Jenkins, L. P.; Brandt, W. N.; Colbert, E. J. M.; Koribalski, B.; Kuntz, K. D.; Levan, A. J.; Ojha, R.; Roberts, T. P.; Ward, M. J.; Zezas, A.

2011-06-01

We have performed an X-ray study of the nearby barred spiral galaxy NGC 1672, primarily to ascertain the effect of the bar on its nuclear activity. We use both Chandra and XMM-Newton observations to investigate its X-ray properties, together with supporting high-resolution optical imaging data from the Hubble Space Telescope (HST), infrared imaging from the Spitzer Space Telescope, and Australia Telescope Compact Array ground-based radio data. We detect 28 X-ray sources within the D 25 area of the galaxy; many are spatially correlated with star formation in the bar and spiral arms, and two are identified as background galaxies in the HST images. Nine of the X-ray sources are ultraluminous X-ray sources, with the three brightest (LX > 5 × 1039 erg s-1) located at the ends of the bar. With the spatial resolution of Chandra, we are able to show for the first time that NGC 1672 possesses a hard (Γ ~ 1.5) nuclear X-ray source with a 2-10 keV luminosity of 4 × 1038 erg s-1. This is surrounded by an X-ray-bright circumnuclear star-forming ring, comprised of point sources and hot gas, which dominates the 2-10 keV emission in the central region of the galaxy. The spatially resolved multiwavelength photometry indicates that the nuclear source is a low-luminosity active galactic nucleus (LLAGN), but with star formation activity close to the central black hole. A high-resolution multiwavelength survey is required to fully assess the impact of both large-scale bars and smaller-scale phenomena such as nuclear bars, rings, and nuclear spirals on the fueling of LLAGN.

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...

Annual report to Congress: Department of Energy activities relating to the Defense Nuclear Facilities Safety Board, calendar year 1998

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

NONE

1999-02-01

This is the ninth Annual Report to the Congress describing Department of Energy (Department) activities in response to formal recommendations and other interactions with the Defense Nuclear Facilities Safety Board (Board). The Board, an independent executive-branch agency established in 1988, provides advice and recommendations to the Secretary of energy regarding public health and safety issues at the Department`s defense nuclear facilities. The Board also reviews and evaluates the content and implementation of health and safety standards, as well as other requirements, relating to the design, construction, operation, and decommissioning of the Department`s defense nuclear facilities. The locations of the majormore » Department facilities are provided. During 1998, Departmental activities resulted in the proposed closure of one Board recommendation. In addition, the Department has completed all implementation plan milestones associated with four other Board recommendations. Two new Board recommendations were received and accepted by the Department in 1998, and two new implementation plans are being developed to address these recommendations. The Department has also made significant progress with a number of broad-based initiatives to improve safety. These include expanded implementation of integrated safety management at field sites, a renewed effort to increase the technical capabilities of the federal workforce, and a revised plan for stabilizing excess nuclear materials to achieve significant risk reduction.« less

Specific repression of β-globin promoter activity by nuclear ferritin

PubMed Central

Broyles, Robert H.; Belegu, Visar; DeWitt, Christina R.; Shah, Sandeep N.; Stewart, Charles A.; Pye, Quentin N.; Floyd, Robert A.

2001-01-01

Developmental hemoglobin switching involves sequential globin gene activations and repressions that are incompletely understood. Earlier observations, described herein, led us to hypothesize that nuclear ferritin is a repressor of the adult β-globin gene in embryonic erythroid cells. Our data show that a ferritin-family protein in K562 cell nuclear extracts binds specifically to a highly conserved CAGTGC motif in the β-globin promoter at −153 to −148 bp from the cap site, and mutation of the CAGTGC motif reduces binding 20-fold in competition gel-shift assays. Purified human ferritin that is enriched in ferritin-H chains also binds the CAGTGC promoter segment. Expression clones of ferritin-H markedly repress β-globin promoter-driven reporter gene expression in cotransfected CV-1 cells in which the β-promoter has been stimulated with the transcription activator erythroid Krüppel-like factor (EKLF). We have constructed chloramphenicol acetyltransferase reporter plasmids containing either a wild-type or mutant β-globin promoter for the −150 CAGTGC motif and have compared the constructs for susceptibility to repression by ferritin-H in cotransfection assays. We find that stimulation by cotransfected EKLF is retained with the mutant promoter, whereas repression by ferritin-H is lost. Thus, mutation of the −150 CAGTGC motif not only markedly reduces in vitro binding of nuclear ferritin but also abrogates the ability of expressed ferritin-H to repress this promoter in our cell transfection assay, providing a strong link between DNA binding and function, and strong support for our proposal that nuclear ferritin-H is a repressor of the human β-globin gene. Such a repressor could be helpful in treating sickle cell and other genetic diseases. PMID:11481480

Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease.

PubMed

Brady, Graham F; Kwan, Raymond; Ulintz, Peter J; Nguyen, Phirum; Bassirian, Shirin; Basrur, Venkatesha; Nesvizhskii, Alexey I; Loomba, Rohit; Omary, M Bishr

2018-05-01

Nonalcoholic fatty liver disease (NAFLD) is becoming the major chronic liver disease in many countries. Its pathogenesis is multifactorial, but twin and familial studies indicate significant heritability, which is not fully explained by currently known genetic susceptibility loci. Notably, mutations in genes encoding nuclear lamina proteins, including lamins, cause lipodystrophy syndromes that include NAFLD. We hypothesized that variants in lamina-associated proteins predispose to NAFLD and used a candidate gene-sequencing approach to test for variants in 10 nuclear lamina-related genes in a cohort of 37 twin and sibling pairs: 21 individuals with and 53 without NAFLD. Twelve heterozygous sequence variants were identified in four lamina-related genes (ZMPSTE24, TMPO, SREBF1, SREBF2). The majority of NAFLD patients (>90%) had at least one variant compared to <40% of controls (P < 0.0001). When only insertions/deletions and changes in conserved residues were considered, the difference between the groups was similarly striking (>80% versus <25%; P < 0.0001). Presence of a lamina variant segregated with NAFLD independently of the PNPLA3 I148M polymorphism. Several variants were found in TMPO, which encodes the lamina-associated polypeptide-2 (LAP2) that has not been associated with liver disease. One of these, a frameshift insertion that generates truncated LAP2, abrogated lamin-LAP2 binding, caused LAP2 mislocalization, altered endogenous lamin distribution, increased lipid droplet accumulation after oleic acid treatment in transfected cells, and led to cytoplasmic association with the ubiquitin-binding protein p62/SQSTM1. Several variants in nuclear lamina-related genes were identified in a cohort of twins and siblings with NAFLD; one such variant, which results in a truncated LAP2 protein and a dramatic phenotype in cell culture, represents an association of TMPO/LAP2 variants with NAFLD and underscores the potential importance of the nuclear lamina in NAFLD

Dry, portable calorimeter for nondestructive measurement of the activity of nuclear fuel

DOEpatents

Beyer, Norman S.; Lewis, Robert N.; Perry, Ronald B.

1976-01-01

The activity of a quantity of heat-producing nuclear fuel is measured rapidly, accurately and nondestructively by a portable dry calorimeter comprising a preheater, an array of temperature-controlled structures comprising a thermally guarded temperature-controlled oven, and a calculation and control unit. The difference between the amounts of electric power required to maintain the oven temperature with and without nuclear fuel in the oven is measured to determine the power produced by radioactive disintegration and hence the activity of the fuel. A portion of the electronic control system is designed to terminate a continuing sequence of measurements when the standard deviation of the variations of the amount of electric power required to maintain oven temperature is within a predetermined value.

Everglades National Park Including Biscayne National Park. Activity Book.

ERIC Educational Resources Information Center

Ruehrwein, Dick

Intended to help elementary school children learn about the resources of the Everglades and Biscayne National Parks, this activity book includes information, puzzles, games, and quizzes. The booklet deals with concepts related to: (1) the seasons; (2) fire ecology; (3) water; (4) fish; (5) mammals; (6) mosquitos; (7) birds; (8) venomous snakes;…

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

Sample registration software for process automation in the Neutron Activation Analysis (NAA) Facility in Malaysia nuclear agency

NASA Astrophysics Data System (ADS)

Rahman, Nur Aira Abd; Yussup, Nolida; Salim, Nazaratul Ashifa Bt. Abdullah; Ibrahim, Maslina Bt. Mohd; Mokhtar, Mukhlis B.; Soh@Shaari, Syirrazie Bin Che; Azman, Azraf B.; Ismail, Nadiah Binti

2015-04-01

Neutron Activation Analysis (NAA) had been established in Nuclear Malaysia since 1980s. Most of the procedures established were done manually including sample registration. The samples were recorded manually in a logbook and given ID number. Then all samples, standards, SRM and blank were recorded on the irradiation vial and several forms prior to irradiation. These manual procedures carried out by the NAA laboratory personnel were time consuming and not efficient. Sample registration software is developed as part of IAEA/CRP project on `Development of Process Automation in the Neutron Activation Analysis (NAA) Facility in Malaysia Nuclear Agency (RC17399)'. The objective of the project is to create a pc-based data entry software during sample preparation stage. This is an effective method to replace redundant manual data entries that needs to be completed by laboratory personnel. The software developed will automatically generate sample code for each sample in one batch, create printable registration forms for administration purpose, and store selected parameters that will be passed to sample analysis program. The software is developed by using National Instruments Labview 8.6.

Investigating the Nuclear Activity of Barred Spiral Galaxies: The Case of NGC 1672

NASA Technical Reports Server (NTRS)

Jenkins, L. P.; Brandt, W. N.; Colbert, E. J.; Koribalski, B.; Kuntz, K. D.; Levan, A. J.; Ojha, R.; Roberts, T. P.; Ward, M. J.; Zezas, A.

2011-01-01

We have performed an X-ray study of the nearby barred spiral galaxy NGC 1672, primarily to ascertain the effect of the bar on its nuclear activity. We use both Chandra and XMM-Newton observations to investigate its X-ray properties, together with supporting high-resolution optical imaging data from the Hubble Space Telescope (HST) infrared imaging from the Spitzer Space Telescope, and Australia Telescope Compact Array ground-based radio data. We detect 28 X-ray sources within the D25 area of the galaxy; many are spatially correlated with star formation in the bar and spiral arms, and two are identified as background galaxies in the HST images. Nine of the X-ray sources are ultraluminous X-ray sources, with the three brightest (LX 5 * 10(exp 39) erg s(exp -1)) located at the ends of the bar. With the spatial resolution of Chandra, we are able to show for the first time that NGC 1672 possesses a hard (1.5) nuclear X-ray source with a 2-10 keV luminosity of 4 * 10(exp 38) erg s(exp -1). This is surrounded by an X-ray-bright circumnuclear star-forming ring, comprised of point sources and hot gas, which dominates the 2-10 keV emission in the central region of the galaxy. The spatially resolved multiwavelength photometry indicates that the nuclear source is a low-luminosity active galactic nucleus (LLAGN), but with star formation activity close to the central black hole. A high-resolution multiwavelength survey is required to fully assess the impact of both large-scale bars and smaller-scale phenomena such as nuclear bars, rings, and nuclear spirals on the fueling of LLAGN.

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.

The origin of the mid-infrared nuclear polarization of active galactic nuclei

NASA Astrophysics Data System (ADS)

Lopez-Rodriguez, E.; Alonso-Herrero, A.; Diaz-Santos, T.; Gonzalez-Martin, O.; Ichikawa, K.; Levenson, N. A.; Martinez-Paredes, M.; Nikutta, R.; Packham, C.; Perlman, E.; Almeida, C. Ramos; Rodriguez-Espinosa, J. M.; Telesco, C. M.

2018-05-01

We combine new (NGC 1275, NGC 4151, and NGC 5506) and previously published (Cygnus A, Mrk 231, and NGC 1068) sub-arcsecond resolution mid-infrared (MIR; 8-13 μm) imaging- and spectro-polarimetric observations of six Seyfert galaxies using CanariCam on the 10.4-m Gran Telescopio CANARIAS. These observations reveal a diverse set of physical processes responsible for the nuclear polarization, and permit characterization of the origin of the MIR nuclear polarimetric signature of active galactic nuclei (AGN). For all radio quiet objects, we found that the nuclear polarization is low (<1 per cent), and the degree of polarization is often a few per cent over extended regions of the host galaxy where we have sensitivity to detect such extended emission (i.e., NGC 1068 and NGC 4151). We suggest that the higher degree of polarization previously found in lower resolution data arises only on the larger-than-nuclear scales. Only the radio-loud Cygnus A exhibits significant nuclear polarization (˜11 per cent), attributable to synchrotron emission from the pc-scale jet close to the core. We present polarization models that suggest that the MIR nuclear polarization for highly obscured objects arises from a self-absorbed MIR polarized clumpy torus and/or dichroism from the host galaxy, while for unabsorbed cores, MIR polarization arises from dust scattering in the torus and/or surrounding nuclear dust.

Evidence for triclosan-induced activation of human and rodent xenobiotic nuclear receptors.

PubMed

Paul, Katie B; Thompson, Jerry T; Simmons, Steven O; Vanden Heuvel, John P; Crofton, Kevin M

2013-10-01

The bacteriostat triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether) (TCS) decreases rat serum thyroxine via putative nuclear receptor (NR) interaction(s) and subsequent transcriptional up-regulation of hepatic catabolism and clearance. However, due to the evolutionary divergence of the constitutive androstane and pregnane-X receptors (CAR, PXR), TCS-mediated downstream effects may be species-dependent. To test the hypothesis that TCS activates xenobiotic NRs across species, cell-based NR reporter assays were employed to assess potential activation of rat, mouse, and human PXR, and rat, mouse, and three splice variants of human CAR. TCS activated hPXR, acted as an inverse agonist of hCAR1, and as a weak agonist of hCAR3. TCS failed to activate rPXR in full-length receptor reporter assays, and instead acted as a modest inverse agonist of rCAR. Consistent with the rat data, TCS also failed to activate mPXR and was a modest inverse agonist of mCAR. These data suggest that TCS may interact with multiple NRs, including hPXR, hCAR1, hCAR3, and rCAR in order to potentially affect hepatic catabolism. Overall these data support the conclusion that TCS may interact with NRs to regulate hepatic catabolism and downstream thyroid hormone homeostasis in both rat and human models, though perhaps by divergent mechanisms. Published by Elsevier Ltd.

Studies of neutron and proton nuclear activation in low-Earth orbit

NASA Technical Reports Server (NTRS)

Laird, C. E.

1982-01-01

The expected induced radioactivity of experimental material in low Earth orbit was studied for characteristics of activating particles such as cosmic rays, high energy Earth albedo neutrons, trapped protons, and secondary protons and neutrons. The activation cross sections for the production of long lived radioisotopes and other existing nuclear data appropriate to the study of these reactions were compiled. Computer codes which are required to calculate the expected activation of orbited materials were developed. The decreased computer code used to predict the activation of trapped protons of materials placed in the expected orbits of LDEF and Spacelab II. Techniques for unfolding the fluxes of activating particles from the measured activation of orbited materials are examined.

Qualitative and Quantitative Assessment of Nuclear Materials Contained in High-Activity Waste Arising from the Operations at the 'SHELTER' Facility

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

Cherkas, Dmytro

2011-10-01

As a result of the nuclear accident at the Chernobyl NPP in 1986, the explosion dispeesed nuclear materials contained in the nuclear fuel of the reactor core over the destroyed facilities at Unit No. 4 and over the territory immediately adjacent to the destroyed unit. The debris was buried under the Cascade Wall. Nuclear materials at the SHELTER can be characterized as spent nuclear fuel, fresh fuel assemblies (including fuel assemblies with damaged geometry and integrity, and individual fuel elements), core fragments of the Chernobyl NPP Unit No. 4, finely-dispersed fuel (powder/dust), uranium and plutonium compounds in water solutions, andmore » lava-like nuclear fuel-containing masses. The new safe confinement (NSC) is a facility designed to enclose the Chernobyl NPP Unit No. 4 destroyed by the accident. Construction of the NSC involves excavating operations, which are continuously monitored including for the level of radiation. The findings of such monitoring at the SHELTER site will allow us to characterize the recovered radioactive waste. When a process material categorized as high activity waste (HAW) is detected the following HLW management operations should be involved: HLW collection; HLW fragmentation (if appropriate); loading HAW into the primary package KT-0.2; loading the primary package filled with HAW into the transportation cask KTZV-0.2; and storing the cask in temporary storage facilities for high-level solid waste. The CDAS system is a system of 3He tubes for neutron coincidence counting, and is designed to measure the percentage ratio of specific nuclear materials in a 200-liter drum containing nuclear material intermixed with a matrix. The CDAS consists of panels with helium counter tubes and a polyethylene moderator. The panels are configured to allow one to position a waste-containing drum and a drum manipulator. The system operates on the ‘add a source’ basis using a small Cf-252 source to identify irregularities in the matrix during

Controlling nuclear JAKs and STATs for specific gene activation by IFNγ.

PubMed

Noon-Song, Ezra N; Ahmed, Chulbul M; Dabelic, Rea; Canton, Johnathan; Johnson, Howard M

2011-07-08

We previously showed that gamma interferon (IFNγ) and its receptor subunit, IFNGR1, interacted with the promoter region of IFNγ-activated genes along with transcription factor STAT1α. Recent studies have suggested that activated Janus kinases pJAK2 and pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFNγ. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFNγ treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The β-actin gene, which is not activated by IFNγ, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFNγ treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFNγ treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFNγ treatment resulted in its disassociation and then re-association as pSTAT1. The results suggest a novel role for activated JAKs in epigenetic events for specific gene activation. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Supernova equations of state including full nuclear ensemble with in-medium effects

NASA Astrophysics Data System (ADS)

Furusawa, Shun; Sumiyoshi, Kohsuke; Yamada, Shoichi; Suzuki, Hideyuki

2017-01-01

We construct new equations of state for baryons at sub-nuclear densities for the use in core-collapse supernova simulations. The abundance of various nuclei is obtained together with thermodynamic quantities. The formulation is an extension of the previous model, in which we adopted the relativistic mean field theory with the TM1 parameter set for nucleons, the quantum approach for d, t, h and α as well as the liquid drop model for the other nuclei under the nuclear statistical equilibrium. We reformulate the model of the light nuclei other than d, t, h and α based on the quasi-particle description. Furthermore, we modify the model so that the temperature dependences of surface and shell energies of heavy nuclei could be taken into account. The pasta phases for heavy nuclei and the Pauli- and self-energy shifts for d, t, h and α are taken into account in the same way as in the previous model. We find that nuclear composition is considerably affected by the modifications in this work, whereas thermodynamical quantities are not changed much. In particular, the washout of shell effect has a great impact on the mass distribution above T ∼ 1 MeV. This improvement may have an important effect on the rates of electron captures and coherent neutrino scatterings on nuclei in supernova cores.

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.

Sensor Fusion for Nuclear Proliferation Activity Monitoring

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

Adel Ghanem, Ph D

2007-03-30

The objective of Phase 1 of this STTR project is to demonstrate a Proof-of-Concept (PoC) of the Geo-Rad system that integrates a location-aware SmartTag (made by ZonTrak) and a radiation detector (developed by LLNL). It also includes the ability to transmit the collected radiation data and location information to the ZonTrak server (ZonService). The collected data is further transmitted to a central server at LLNL (the Fusion Server) to be processed in conjunction with overhead imagery to generate location estimates of nuclear proliferation and radiation sources.

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

Neutron monitoring systems including gamma thermometers and methods of calibrating nuclear instruments using gamma thermometers

DOEpatents

Moen, Stephan Craig; Meyers, Craig Glenn; Petzen, John Alexander; Foard, Adam Muhling

2012-08-07

A method of calibrating a nuclear instrument using a gamma thermometer may include: measuring, in the instrument, local neutron flux; generating, from the instrument, a first signal proportional to the neutron flux; measuring, in the gamma thermometer, local gamma flux; generating, from the gamma thermometer, a second signal proportional to the gamma flux; compensating the second signal; and calibrating a gain of the instrument based on the compensated second signal. Compensating the second signal may include: calculating selected yield fractions for specific groups of delayed gamma sources; calculating time constants for the specific groups; calculating a third signal that corresponds to delayed local gamma flux based on the selected yield fractions and time constants; and calculating the compensated second signal by subtracting the third signal from the second signal. The specific groups may have decay time constants greater than 5.times.10.sup.-1 seconds and less than 5.times.10.sup.5 seconds.

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.

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

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

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.

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...

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.

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.

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.

Changes in the size and synthetic activity of nuclear populations in chronically stimulated rabbit skeletal muscle.

PubMed Central

Joplin, R E; Franchi, L L; Salmons, S

1987-01-01

The adaptive response of mammalian fast-twitch skeletal muscle to long-term low-frequency stimulation involves coordinated changes in the expression of a large number of genes and an increase in the synthesis of proteins and nucleic acids. Morphological correlates of these changes were sought in a qualitative and quantitative study of nuclear populations that included autoradiography at both light and electron microscopic levels. Stimulation-induced changes in biosynthetic activity were found to be supported by increases in the numbers of both non-muscle and muscle nuclei, and myonuclear counts were significantly increased in relation to sarcoplasmic volume. Moreover, the chronically stimulated muscle fibres showed ultrastructural signs consistent with mobilisation of transcriptional and translational activity. Images Fig. 2 Fig. 4 (cont.) Fig. 4 Fig. 5 PMID:3503051

Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors.

PubMed

Mills, Ian G; Gaughan, Luke; Robson, Craig; Ross, Theodora; McCracken, Stuart; Kelly, John; Neal, David E

2005-07-18

Internalization of activated receptors regulates signaling, and endocytic adaptor proteins are well-characterized in clathrin-mediated uptake. One of these adaptor proteins, huntingtin interacting protein 1 (HIP1), induces cellular transformation and is overexpressed in some prostate cancers. We have discovered that HIP1 associates with the androgen receptor through a central coiled coil domain and is recruited to DNA response elements upon androgen stimulation. HIP1 is a novel androgen receptor regulator, significantly repressing transcription when knocked down using a silencing RNA approach and activating transcription when overexpressed. We have also identified a functional nuclear localization signal at the COOH terminus of HIP1, which contributes to the nuclear translocation of the protein. In conclusion, we have discovered that HIP1 is a nucleocytoplasmic protein capable of associating with membranes and DNA response elements and regulating transcription.

Huntingtin interacting protein 1 modulates the transcriptional activity of nuclear hormone receptors

PubMed Central

Mills, Ian G.; Gaughan, Luke; Robson, Craig; Ross, Theodora; McCracken, Stuart; Kelly, John; Neal, David E.

2005-01-01

Internalization of activated receptors regulates signaling, and endocytic adaptor proteins are well-characterized in clathrin-mediated uptake. One of these adaptor proteins, huntingtin interacting protein 1 (HIP1), induces cellular transformation and is overexpressed in some prostate cancers. We have discovered that HIP1 associates with the androgen receptor through a central coiled coil domain and is recruited to DNA response elements upon androgen stimulation. HIP1 is a novel androgen receptor regulator, significantly repressing transcription when knocked down using a silencing RNA approach and activating transcription when overexpressed. We have also identified a functional nuclear localization signal at the COOH terminus of HIP1, which contributes to the nuclear translocation of the protein. In conclusion, we have discovered that HIP1 is a nucleocytoplasmic protein capable of associating with membranes and DNA response elements and regulating transcription. PMID:16027218

Nuclear rocket propulsion. NASA plans and progress, FY 1991

NASA Technical Reports Server (NTRS)

Clark, John S.; Miller, Thomas J.

1991-01-01

NASA has initiated planning for a technology development project for nuclear rocket propulsion systems for space explorer initiative (SEI) human and robotic missions to the moon and Mars. An interagency project is underway that includes the Department of Energy National Laboratories for nuclear technology development. The activities of the project planning team in FY 1990 and 1991 are summarized. The progress to date is discussed, and the project plan is reviewed. Critical technology issues were identified and include: (1) nuclear fuel temperature, life, and reliability; (2) nuclear system ground test; (3) safety; (4) autonomous system operation and health monitoring; and (5) minimum mass and high specific impulse.

Nuclear rocket propulsion: NASA plans and progress - FY 1991

NASA Technical Reports Server (NTRS)

Clark, John S.; Miller, Thomas J.

1991-01-01

NASA has initiated planning for a technology development project for nuclear rocket propulsion systems for space exploration initiative (SEI) human and robotic missions to the Moon and to Mars. An interagency project is underway that includes the Department of Energy National Laboratories for nuclear technology development. The activities of the project planning team in FY 1990 and 1991 are summarized. The progress to date is discussed, and the project plan is reviewed. Critical technology issues were identified and include: (1) nuclear fuel temperature, life, and reliability; (2) nuclear system ground test; (3) safety; (4) autonomous system operation and health monitoring; and (5) minimum mass and high specific impulse.

Nuclear Power Now and in the Near Future

NASA Astrophysics Data System (ADS)

Burchill, William

2006-04-01

The presentation will describe the present status of nuclear power in the United States including its operating, economic, and safety record. This status report will be based on publicly-available records of the U.S. Department of Energy, the U.S. Nuclear Regulatory Commission, and the Institute of Nuclear Power Operations. The report will provide a brief description and state the impact of both the Three Mile Island and Chernobyl accidents. It will list the lessons learned and report significant improvements in U.S. nuclear power plants. The major design differences between Chernobyl and U.S. nuclear reactors will be discussed. The presentation will project the near future of nuclear power considering the 2005 Energy Bill, initiatives by the U.S. Department of Energy and industry, and public opinions. Issues to be considered include plant operating safety, disposition of nuclear waste, protection against proliferation of potential weapons materials, economic performance, environmental impact and protection, and advanced nuclear reactor designs and fuel cycle options. The risk of nuclear power plant operations will be compared to risks presented by other industrial activities.

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.

SREBF1 Activity is Regulated by an AR/mTOR Nuclear Axis in Prostate Cancer.

PubMed

Audet-Walsh, Etienne; Vernier, Mathieu; Yee, Tracey; Laflamme, Chloe E; Li, Susan; Chen, Yonghong; Giguere, Vincent

2018-05-21

Reprogramming of cellular metabolism is an important feature of prostate cancer (PCa), including altered lipid metabolism. Recently, it was observed that the nuclear fraction of mTOR is essential for the androgen-mediated metabolic reprogramming of PCa cells. Herein, it is demonstrated that the androgen receptor (AR) and mTOR bind to regulatory regions of sterol regulatory element binding transcription factor 1 (SREBF1) to control its expression, while dual activation of these signaling pathways also promotes SREBF1 cleavage and its translocation to the nucleus. Consequently, SREBF1 recruitment to regulatory regions of its target genes is induced upon treatment with the synthetic androgen R1881, an effect abrogated upon inhibition of the mTOR signaling pathway. In turn, pharmacological and genetic inhibition of SREBF1 activity impairs the androgen-mediated induction of the key lipogenic genes fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD1). Consistent with these observations, the expression of SREBF1, FASN and SCD1 is significantly correlated in human PCa tumor clinical specimens. Functionally, blockade of SREBF1 activity reduces the androgen-driven lipid accumulation. Interestingly, decreased triglyceride accumulation observed upon SREBF1 inhibition is paralleled by an increase in mitochondrial respiration, indicating a potential rewiring of citrate metabolism in PCa cells. Altogether, these data define an AR/mTOR nuclear axis, in the context of PCa, as a novel pathway regulating SREBF1 activity and citrate metabolism. The finding that an AR/mTOR complex promotes SREBP expression and activity enhances our understanding of the metabolic adaptation necessary for prostate cancer cell growth and suggests novel therapeutic approaches to target metabolic vulnerabilities in tumors. Copyright ©2018, American Association for Cancer Research.

Diversity of the Arabidopsis mitochondrial genome occurs via nuclear-controlled recombination activity.

PubMed

Arrieta-Montiel, Maria P; Shedge, Vikas; Davila, Jaime; Christensen, Alan C; Mackenzie, Sally A

2009-12-01

The plant mitochondrial genome is recombinogenic, with DNA exchange activity controlled to a large extent by nuclear gene products. One nuclear gene, MSH1, appears to participate in suppressing recombination in Arabidopsis at every repeated sequence ranging in size from 108 to 556 bp. Present in a wide range of plant species, these mitochondrial repeats display evidence of successful asymmetric DNA exchange in Arabidopsis when MSH1 is disrupted. Recombination frequency appears to be influenced by repeat sequence homology and size, with larger size repeats corresponding to increased DNA exchange activity. The extensive mitochondrial genomic reorganization of the msh1 mutant produced altered mitochondrial transcription patterns. Comparison of mitochondrial genomes from the Arabidopsis ecotypes C24, Col-0, and Ler suggests that MSH1 activity accounts for most or all of the polymorphisms distinguishing these genomes, producing ecotype-specific stoichiometric changes in each line. Our observations suggest that MSH1 participates in mitochondrial genome evolution by influencing the lineage-specific pattern of mitochondrial genetic variation in higher plants.

Salicylates inhibit flavivirus replication independently of blocking nuclear factor kappa B activation.

PubMed

Liao, C L; Lin, Y L; Wu, B C; Tsao, C H; Wang, M C; Liu, C I; Huang, Y L; Chen, J H; Wang, J P; Chen, L K

2001-09-01

Flaviviruses comprise a positive-sense RNA genome that replicates exclusively in the cytoplasm of infected cells. Whether flaviviruses require an activated nuclear factor(s) to complete their life cycle and trigger apoptosis in infected cells remains elusive. Flavivirus infections quickly activate nuclear factor kappa B (NF-kappaB), and salicylates have been shown to inhibit NF-kappaB activation. In this study, we investigated whether salicylates suppress flavivirus replication and virus-induced apoptosis in cultured cells. In a dose-dependent inhibition, we found salicylates within a range of 1 to 5 mM not only restricted flavivirus replication but also abrogated flavivirus-triggered apoptosis. However, flavivirus replication was not affected by a specific NF-kappaB peptide inhibitor, SN50, and a proteosome inhibitor, lactacystin. Flaviviruses also replicated and triggered apoptosis in cells stably expressing IkappaBalpha-DeltaN, a dominant-negative mutant that antagonizes NF-kappaB activation, as readily as in wild-type BHK-21 cells, suggesting that NF-kappaB activation is not essential for either flavivirus replication or flavivirus-induced apoptosis. Salicylates still diminished flavivirus replication and blocked apoptosis in the same IkappaBalpha-DeltaN cells. This inhibition of flaviviruses by salicylates could be partially reversed by a specific p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580. Together, these results show that the mechanism by which salicylates suppress flavivirus infection may involve p38 MAP kinase activity but is independent of blocking the NF-kappaB pathway.

A transgenerational role of the germline nuclear RNAi pathway in repressing heat stress-induced transcriptional activation in C. elegans.

PubMed

Ni, Julie Zhouli; Kalinava, Natallia; Chen, Esteban; Huang, Alex; Trinh, Thi; Gu, Sam Guoping

2016-01-01

Environmental stress-induced transgenerational epigenetic effects have been observed in various model organisms and human. The capacity and mechanism of such phenomena are poorly understood. In C. elegans, siRNA mediates transgenerational gene silencing through the germline nuclear RNAi pathway. This pathway is also required to maintain the germline immortality when C. elegans is under heat stress. However, the underlying molecular mechanism is unknown. In this study, we investigated the impact of heat stress on chromatin, transcription, and siRNAs at the whole-genome level, and whether any of the heat-induced effects is transgenerationally heritable in either the wild-type or the germline nuclear RNAi mutant animals. We performed 12-generation temperature-shift experiments using the wild-type C. elegans and a mutant strain that lacks the germline-specific nuclear Argonaute protein HRDE-1/WAGO-9. By examining the mRNA, small RNA, RNA polymerase II, and H3K9 trimethylation profiles at the whole-genome level, we revealed an epigenetic role of HRDE-1 in repressing heat stress-induced transcriptional activation of over 280 genes. Many of these genes are in or near LTR (long-terminal repeat) retrotransposons. Strikingly, for some of these genes, the heat stress-induced transcriptional activation in the hrde-1 mutant intensifies in the late generations under the heat stress and is heritable for at least two generations after the mutant animals are shifted back to lower temperature. hrde-1 mutation also leads to siRNA expression changes of many genes. This effect on siRNA is dependent on both the temperature and generation. Our study demonstrated that a large number of the endogenous targets of the germline nuclear RNAi pathway in C. elegans are sensitive to heat-induced transcriptional activation. This effect at certain genomic loci including LTR retrotransposons is transgenerational. Germline nuclear RNAi antagonizes this temperature effect at the transcriptional level

Nuclear p21-activated kinase 1 in breast cancer packs off tamoxifen sensitivity.

PubMed

Rayala, Suresh K; Molli, Poonam R; Kumar, Rakesh

2006-06-15

There is significant clinical interest in the factors that influence the development of tamoxifen resistance in estrogen receptor-alpha (ER-alpha)-positive breast cancers. Recent studies suggest that in ER-positive breast tumor cells, elevated protein levels, and in particular, nuclear localization of p21-activated kinase 1 (PAK1), is associated with the progressive limitation of tamoxifen sensitivity. These phenotypic effects of PAK1 in model systems are mechanistically linked with the ability of PAK1 to phosphorylate ER-alpha on serine 305 and subsequent secondary activation of serine 118. These findings prompt further investigation of how nuclear signaling by PAK1 may affect estrogen's action and whether tamoxifen resistance might be prevented or reversed by PAK1 inhibition.

Nuclear fuel pin scanner

DOEpatents

Bramblett, Richard L.; Preskitt, Charles A.

1987-03-03

Systems and methods for inspection of nuclear fuel pins to determine fiss loading and uniformity. The system includes infeed mechanisms which stockpile, identify and install nuclear fuel pins into an irradiator. The irradiator provides extended activation times using an approximately cylindrical arrangement of numerous fuel pins. The fuel pins can be arranged in a magazine which is rotated about a longitudinal axis of rotation. A source of activating radiation is positioned equidistant from the fuel pins along the longitudinal axis of rotation. The source of activating radiation is preferably oscillated along the axis to uniformly activate the fuel pins. A detector is provided downstream of the irradiator. The detector uses a plurality of detector elements arranged in an axial array. Each detector element inspects a segment of the fuel pin. The activated fuel pin being inspected in the detector is oscillated repeatedly over a distance equal to the spacing between adjacent detector elements, thereby multiplying the effective time available for detecting radiation emissions from the activated fuel pin.

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

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.

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.

Sample registration software for process automation in the Neutron Activation Analysis (NAA) Facility in Malaysia nuclear agency

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

Rahman, Nur Aira Abd, E-mail: nur-aira@nuclearmalaysia.gov.my; Yussup, Nolida; Ibrahim, Maslina Bt. Mohd

Neutron Activation Analysis (NAA) had been established in Nuclear Malaysia since 1980s. Most of the procedures established were done manually including sample registration. The samples were recorded manually in a logbook and given ID number. Then all samples, standards, SRM and blank were recorded on the irradiation vial and several forms prior to irradiation. These manual procedures carried out by the NAA laboratory personnel were time consuming and not efficient. Sample registration software is developed as part of IAEA/CRP project on ‘Development of Process Automation in the Neutron Activation Analysis (NAA) Facility in Malaysia Nuclear Agency (RC17399)’. The objective ofmore » the project is to create a pc-based data entry software during sample preparation stage. This is an effective method to replace redundant manual data entries that needs to be completed by laboratory personnel. The software developed will automatically generate sample code for each sample in one batch, create printable registration forms for administration purpose, and store selected parameters that will be passed to sample analysis program. The software is developed by using National Instruments Labview 8.6.« less

Controlling nuclear RNA levels.

PubMed

Schmid, Manfred; Jensen, Torben Heick

2018-05-10

RNA turnover is an integral part of cellular RNA homeostasis and gene expression regulation. Whereas the cytoplasmic control of protein-coding mRNA is often the focus of study, we discuss here the less appreciated role of nuclear RNA decay systems in controlling RNA polymerase II (RNAPII)-derived transcripts. Historically, nuclear RNA degradation was found to be essential for the functionalization of transcripts through their proper maturation. Later, it was discovered to also be an important caretaker of nuclear hygiene by removing aberrant and unwanted transcripts. Recent years have now seen a set of new protein complexes handling a variety of new substrates, revealing functions beyond RNA processing and the decay of non-functional transcripts. This includes an active contribution of nuclear RNA metabolism to the overall cellular control of RNA levels, with mechanistic implications during cellular transitions.

Soviet steam generator technology: fossil fuel and nuclear power plants. [Glossary included

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

Rosengaus, J.

1987-01-01

In the Soviet Union, particular operational requirements, coupled with a centralized planning system adopted in the 1920s, have led to a current technology which differs in significant ways from its counterparts elsewhere in the would and particularly in the United States. However, the monograph has a broader value in that it traces the development of steam generators in response to the industrial requirements of a major nation dealing with the global energy situation. Specifically, it shows how Soviet steam generator technology evolved as a result of changing industrial requirements, fuel availability, and national fuel utilization policy. The monograph begins withmore » a brief technical introduction focusing on steam-turbine power plants, and includes a discussion of the Soviet Union's regional power supply (GRES) networks and heat and power plant (TETs) systems. TETs may be described as large central co-generating stations which, in addition to electricity, provide heat in the form of steam and hot water. Plants of this type are a common feature of the USSR today. The adoption of these cogeneration units as a matter of national policy has had a central influence on Soviet steam generator technology which can be traced throughout the monograph. The six chapters contain: a short history of steam generators in the USSR; steam generator design and manufacture in the USSR; boiler and furnace assemblies for fossil fuel-fired power stations; auxiliary components; steam generators in nuclear power plants; and the current status of the Soviet steam generator industry. Chapters have been abstracted separately. A glossary is included containing abbreviations and acronyms of USSR organizations. 26 references.« less

Nuclear Factor Kappa B Activation and Peroxisome Proliferator-activated Receptor Transactivational Effects of Chemical Components of the Roots of Polygonum multiflorum.

PubMed

Sun, Ya Nan; Li, Wei; Song, Seok Bean; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

2016-01-01

Polygonum multiflorum is well-known as "Heshouwu" in traditional Chinese herbal medicine. In Northeast Asia, it is often used as a tonic to prevent premature aging of the kidney and liver, tendons, and bones and strengthening of the lower back and knees. To research the anti-inflammatory activities of components from P. multiflorum. The compounds were isolated by a combination of silica gel and YMC R-18 column chromatography, and their structures were identified by analysis of spectroscopic data (1D, 2D-nuclear magnetic resonance, and mass spectrometry). The anti-inflammatory activities of the isolated compounds 1-15 were evaluated by luciferase reporter gene assays. Fifteen compounds (1-15) were isolated from the roots of P. multiflorum. Compounds 1-5 and 14-15 significantly inhibited tumor necrosis factor-α-induced nuclear factor kappa B-luciferase activity, with IC50 values of 24.16-37.56 μM. Compounds 1-5 also greatly enhanced peroxisome proliferator-activated receptors transcriptional activity with EC50 values of 18.26-31.45 μM. The anthraquinone derivatives were the active components from the roots of P. multiflorum as an inhibitor on inflammation-related factors in human hepatoma cells. Therefore, we suggest that the roots of P. multiflorum can be used to treat natural inflammatory diseases. This study presented that fifteen compounds (1-15) isolated from the roots of Polygonum multiflrum exert signifiant anti inflmmatory effects by inhibiting TNF α induced NF κB activation and PPARs transcription. Abbreviation used: NF κB: Nuclear factor kappa B, PPARs: Peroxisome proliferator activated receptors, PPREs: Peroxisome proliferator response elements, TNF α: Tumor necrosis factor α, ESI-MS: Electrospray ionization mass spectrometry, HepG2: Human hepatoma cells.

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.

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.

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.

History of Nuclear India

NASA Astrophysics Data System (ADS)

Chaturvedi, Ram

2000-04-01

India emerged as a free and democratic country in 1947, and entered into the nuclear age in 1948 by establishing the Atomic Energy Commission (AEC), with Homi Bhabha as the chairman. Later on the Department of Atomic Energy (DAE) was created under the Office of the Prime Minister Jawahar Lal Nehru. Initially the AEC and DAE received international cooperation, and by 1963 India had two research reactors and four nuclear power reactors. In spite of the humiliating defeat in the border war by China in 1962 and China's nuclear testing in 1964, India continued to adhere to the peaceful uses of nuclear energy. On May 18, 1974 India performed a 15 kt Peaceful Nuclear Explosion (PNE). The western powers considered it nuclear weapons proliferation and cut off all financial and technical help, even for the production of nuclear power. However, India used existing infrastructure to build nuclear power reactors and exploded both fission and fusion devices on May 11 and 13, 1998. The international community viewed the later activity as a serious road block for the Non-Proliferation Treaty and the Comprehensive Test Ban Treaty; both deemed essential to stop the spread of nuclear weapons. India considers these treaties favoring nuclear states and is prepared to sign if genuine nuclear disarmament is included as an integral part of these treaties.

Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity

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

Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun

Endogenous viral elements (EVE) in animal genomes are the fossil records of ancient viruses and provide invaluable information on the origin and evolution of extant viruses. Extant hepadnaviruses include avihepadnaviruses of birds and orthohepadnaviruses of mammals. The core promoter (Cp) of hepadnaviruses is vital for viral gene expression and replication. We previously identified in the budgerigar genome two EVEs that contain the full-length genome of an ancient budgerigar hepadnavirus (eBHBV1 and eBHBV2). Here, we found eBHBV1 Cp and eBHBV2 Cp were active in several human and chicken cell lines. A region from nt −85 to −11 in eBHBV1 Cp was critical formore » the promoter activity. Bioinformatic analysis revealed a putative binding site of nuclear factor Y (NF-Y), a ubiquitous transcription factor, at nt −64 to −50 in eBHBV1 Cp. The NF-Y core binding site (ATTGG, nt −58 to −54) was essential for eBHBV1 Cp activity. The same results were obtained with eBHBV2 Cp and duck hepatitis B virus Cp. The subunit A of NF-Y (NF-YA) was recruited via the NF-Y core binding site to eBHBV1 Cp and upregulated the promoter activity. Finally, the NF-Y core binding site is conserved in the Cps of all the extant avihepadnaviruses but not of orthohepadnaviruses. Interestingly, a putative and functionally important NF-Y core binding site is located at nt −21 to −17 in the Cp of human hepatitis B virus. In conclusion, our findings have pinpointed an evolutionary conserved and functionally critical NF-Y binding element in the Cps of avihepadnaviruses. - Highlights: • Endogenous budgerigar hepadnavirus (eBHBV) core promoters (Cps) are active in cells. • NF-Y binding site exists in the Cps of eBHBVs and all the extant avihepadnaviruses. • NF-Y binding and mediated upregulation is critical for eBHBV Cp activity.« less

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

An overview of research activities on materials for nuclear applications at the INL Safety, Tritium and Applied Research facility

NASA Astrophysics Data System (ADS)

Calderoni, P.; Sharpe, J.; Shimada, M.; Denny, B.; Pawelko, B.; Schuetz, S.; Longhurst, G.; Hatano, Y.; Hara, M.; Oya, Y.; Otsuka, T.; Katayama, K.; Konishi, S.; Noborio, K.; Yamamoto, Y.

2011-10-01

The Safety, Tritium and Applied Research facility at the Idaho National Laboratory is a US Department of Energy National User Facility engaged in various aspects of materials research for nuclear applications related to fusion and advanced fission systems. Research activities are mainly focused on the interaction of tritium with materials, in particular plasma facing components, liquid breeders, high temperature coolants, fuel cladding, cooling and blanket structures and heat exchangers. Other activities include validation and verification experiments in support of the Fusion Safety Program, such as beryllium dust reactivity and dust transport in vacuum vessels, and support of Advanced Test Reactor irradiation experiments. This paper presents an overview of the programs engaged in the activities, which include the US-Japan TITAN collaboration, the US ITER program, the Next Generation Power Plant program and the tritium production program, and a presentation of ongoing experiments as well as a summary of recent results with emphasis on fusion relevant materials.

Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan.

PubMed

Silvestrini, Melissa J; Johnson, Joseph R; Kumar, Anita V; Thakurta, Tara G; Blais, Karine; Neill, Zachary A; Marion, Sarah W; St Amand, Victoria; Reenan, Robert A; Lapierre, Louis R

2018-05-15

Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 inhibitors recapitulated the effect on autophagy and lifespan observed by silencing xpo-1 and protected ALS-afflicted flies from neurodegeneration. XPO1 inhibition in HeLa cells enhanced TFEB nuclear localization, autophagy, and lysosome biogenesis without affecting mTOR activity, revealing a conserved regulatory mechanism for HLH-30/TFEB. Altogether, our study demonstrates that altering the nuclear export of HLH-30/TFEB can regulate autophagy and establishes the rationale of targeting XPO1 to stimulate autophagy in order to prevent neurodegeneration. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

OVERVIEW OF THE ACTIVITIES OF THE NUCLEAR ENERGY AGENCY WORKING GROUP ON EXTERNAL EVENTS

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

Nakoski, John A.; Smith, Curtis L.; Kim, Min Kyu

The Orgranisation for Economic Cooperation and Development (OECD) Nuclear Energy Agency (NEA) has established a Working Group on External Events (WGEV) that provides a forum for subject matter experts from the nuclear industry and regulators to improve the understanding and treatment of external hazards that would support the continued safety performance of nuclear installations, and improve the effectiveness of regulatory practices, in NEA member countries. This report provides a description of the ongoing work of the WGEV. The work of the WGEV includes the collection of information and conducting a workshop on severe weather and storm surge that brought togethermore » a diverse group of subject matter experts to identify commendable practices related to the treatment of severe weather and storm surge consideration in regulatory and operational decision-making. Other work of the WGEV includes looking at science-based screening of external events that are factored into decisions on the safe operation of nuclear facilities; and identification of commendable practices and knowledge gaps on riverine flooding.« less

Retinoids induce integrin-independent lymphocyte adhesion through RAR-α nuclear receptor activity

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

Whelan, Jarrett T.; Wang, Lei; Chen, Jianming

2014-11-28

Highlights: • Transcription and translation are required for retinoid-induced lymphocyte adhesion. • RAR activation is sufficient to induced lymphocyte cell adhesion. • Vitamin D derivatives inhibit RAR-prompted lymphocyte adhesion. • Adhesion occurs through a novel binding site within ADAM disintegrin domains. • RARα is a key nuclear receptor for retinoid-dependent lymphocyte cell adhesion. - Abstract: Oxidative metabolites of vitamin A, in particular all-trans-retinoic acid (atRA), have emerged as key factors in immunity by specifying the localization of immune cells to the gut. Although it is appreciated that isomers of retinoic acid activate the retinoic acid receptor (RAR) and retinoid Xmore » receptor (RXR) family of nuclear receptors to elicit cellular changes, the molecular details of retinoic acid action remain poorly defined in immune processes. Here we employ a battery of agonists and antagonists to delineate the specific nuclear receptors utilized by retinoids to evoke lymphocyte cell adhesion to ADAM (adisintegrin and metalloprotease) protein family members. We report that RAR agonism is sufficient to promote immune cell adhesion in both immortal and primary immune cells. Interestingly, adhesion occurs independent of integrin function, and mutant studies demonstrate that atRA-induced adhesion to ADAM members required a distinct binding interface(s) as compared to integrin recognition. Anti-inflammatory corticosteroids as well as 1,25-(OH){sub 2}D{sub 3}, a vitamin D metabolite that prompts immune cell trafficking to the skin, potently inhibited the observed adhesion. Finally, our data establish that induced adhesion was specifically attributable to the RAR-α receptor isotype. The current study provides novel molecular resolution as to which nuclear receptors transduce retinoid exposure into immune cell adhesion.« less

Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

PubMed Central

Gravina, Giovanni Luca; Mancini, Andrea; Colapietro, Alessandro; Marampon, Francesco; Sferra, Roberta; Pompili, Simona; Biordi, Leda Assunta; Iorio, Roberto; Flati, Vincenzo; Argueta, Christian; Landesman, Yosef; Kauffman, Michael; Shacham, Sharon; Festuccia, Claudio

2017-01-01

Background and aims Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives. Results and conclusions We show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients. PMID:29340049

The Harnessed Atom: Nuclear Energy & Electricity.

ERIC Educational Resources Information Center

Department of Energy, Washington, DC. Nuclear Energy Office.

This document is part of a nuclear energy curriculum designed for grades six through eight. The complete kit includes a written text, review exercises, activities for the students, and a teachers guide. The 19 lessons in the curriculum are divided into four units including: (1) "Energy and Electricity"; (2) "Understanding Atoms and Radiation"; (3)…

Targeting Nuclear Receptors with Marine Natural Products

PubMed Central

Yang, Chunyan; Li, Qianrong; Li, Yong

2014-01-01

Nuclear receptors (NRs) are important pharmaceutical targets because they are key regulators of many metabolic and inflammatory diseases, including diabetes, dyslipidemia, cirrhosis, and fibrosis. As ligands play a pivotal role in modulating nuclear receptor activity, the discovery of novel ligands for nuclear receptors represents an interesting and promising therapeutic approach. The search for novel NR agonists and antagonists with enhanced selectivities prompted the exploration of the extraordinary chemical diversity associated with natural products. Recent studies involving nuclear receptors have disclosed a number of natural products as nuclear receptor ligands, serving to re-emphasize the translational possibilities of natural products in drug discovery. In this review, the natural ligands of nuclear receptors will be described with an emphasis on their mechanisms of action and their therapeutic potentials, as well as on strategies to determine potential marine natural products as nuclear receptor modulators. PMID:24473166

The nuclear arsenals and nuclear disarmament.

PubMed

Barnaby, F

1998-01-01

Current world stockpiles of nuclear weapons and the status of treaties for nuclear disarmament and the ultimate elimination of nuclear weapons are summarised. The need for including stockpiles of civil plutonium in a programme for ending production and disposing of fissile materials is emphasized, and the ultimate difficulty of disposing of the last few nuclear weapons discussed.

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 Physics Research Activity Today in the World and in Brazil

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

Lepine-Szily, Alinka

2009-06-03

The international effort in Nuclear Physics is described, including informations on working force, its evolution, budgets, existing, new and projected facilities. The main goals of this research and its recent achievements are also presented. The specific informations on Brazil are also highlighted in the presentation.

Natural chemical shielding analysis of nuclear magnetic resonance shielding tensors from gauge-including atomic orbital calculations

NASA Astrophysics Data System (ADS)

Bohmann, Jonathan A.; Weinhold, Frank; Farrar, Thomas C.

1997-07-01

Nuclear magnetic shielding tensors computed by the gauge including atomic orbital (GIAO) method in the Hartree-Fock self-consistent-field (HF-SCF) framework are partitioned into magnetic contributions from chemical bonds and lone pairs by means of natural chemical shielding (NCS) analysis, an extension of natural bond orbital (NBO) analysis. NCS analysis complements the description provided by alternative localized orbital methods by directly calculating chemical shieldings due to delocalized features in the electronic structure, such as bond conjugation and hyperconjugation. Examples of NCS tensor decomposition are reported for CH4, CO, and H2CO, for which a graphical mnemonic due to Cornwell is used to illustrate the effect of hyperconjugative delocalization on the carbon shielding.

Spent Nuclear Fuel Disposition

DOE PAGES

Wagner, John C.

2016-05-22

One interdisciplinary field devoted to achieving the end-state of used nuclear fuel (UNF) through reuse and/or permanent disposal. The reuse option aims to make use of the remaining energy content in UNF and reduce the amount of long-lived radioactive materials that require permanent disposal. The planned approach in the U.S., as well as in many other countries worldwide, is direct permanent disposal in a deep geologic repository. Used nuclear fuel is fuel that has been irradiated in a nuclear reactor to the point where it is no longer capable of sustaining operational objectives. The vast majority (by mass) of UNFmore » is from electricity generation in commercial nuclear power reactors. Furthermore, the other main source of UNF in the U.S. is the Department of Energy’s (DOE) and other federal agencies’ operation of reactors in support of federal government missions, such as materials production, nuclear propulsion, research, testing, and training. Upon discharge from a reactor, UNF emits considerable heat from radioactive decay. Some period of active on-site cooling (e.g., 2 or more years) is typically required to facilitate efficient packaging and transportation to a disposition facility. Hence, the field of UNF disposition broadly includes storage, transportation and ultimate disposition. See also: Nuclear Fission (content/nuclear-fission/458400), Nuclear Fuels (/content/nuclear-fuels/458600), Nuclear Fuel Cycle (/content/nuclear-fuel-cycle/458500), Nuclear Fuels Reprocessing (/content/nuclear-fuels-reprocessing/458700), Nuclear Power (/content/nuclear-power/459600), Nuclear Reactor (/content/nuclear-reactor/460100), Radiation (/content/radiation/566300), and Radioactive Waste Management (/content/radioactive-waste-management/568900).« less

Spent Nuclear Fuel Disposition

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

Wagner, John C.

One interdisciplinary field devoted to achieving the end-state of used nuclear fuel (UNF) through reuse and/or permanent disposal. The reuse option aims to make use of the remaining energy content in UNF and reduce the amount of long-lived radioactive materials that require permanent disposal. The planned approach in the U.S., as well as in many other countries worldwide, is direct permanent disposal in a deep geologic repository. Used nuclear fuel is fuel that has been irradiated in a nuclear reactor to the point where it is no longer capable of sustaining operational objectives. The vast majority (by mass) of UNFmore » is from electricity generation in commercial nuclear power reactors. Furthermore, the other main source of UNF in the U.S. is the Department of Energy’s (DOE) and other federal agencies’ operation of reactors in support of federal government missions, such as materials production, nuclear propulsion, research, testing, and training. Upon discharge from a reactor, UNF emits considerable heat from radioactive decay. Some period of active on-site cooling (e.g., 2 or more years) is typically required to facilitate efficient packaging and transportation to a disposition facility. Hence, the field of UNF disposition broadly includes storage, transportation and ultimate disposition. See also: Nuclear Fission (content/nuclear-fission/458400), Nuclear Fuels (/content/nuclear-fuels/458600), Nuclear Fuel Cycle (/content/nuclear-fuel-cycle/458500), Nuclear Fuels Reprocessing (/content/nuclear-fuels-reprocessing/458700), Nuclear Power (/content/nuclear-power/459600), Nuclear Reactor (/content/nuclear-reactor/460100), Radiation (/content/radiation/566300), and Radioactive Waste Management (/content/radioactive-waste-management/568900).« less

Experimental Observations of Nuclear Activity in Deuterated Materials Subjected to a Low-Energy Photon Beam

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Benyo, Theresa L.; Pines, Vladimir; Pines, Marianna; Forsley, Lawrence P.; Westmeyer, Paul A.; Chait, Arnon; Becks, Michael D.; Martin, Richard E.; Hendricks, Robert C.;

Endothelin-1 Expression Associated with Lipid Peroxidation and Nuclear Factor-κB Activation in Type 2 Diabetes Mellitus Patients with Angiopathy and Limb Amputation.

PubMed

Kuo, Yur-Ren; Chien, Ching-Ming; Kuo, Ming-Jen; Wang, Feng-Sheng; Huang, Eng-Yen; Wang, Ching-Jen

2016-01-01

It is unclear whether diabetic angiopathy is related to oxidative stress-associated endothelial dysfunction. The authors investigated whether alteration of endothelin-1 and lipid peroxide production and activation of nuclear factor-κB expression were involved in lower limb amputation in type 2 diabetes mellitus patients. A total of 135 subjects including 51 type 2 diabetes mellitus patients with major lower extremity amputations and 36 diabetes mellitus patients without limb and vascular complication and 48 normal controls were recruited for this study. The authors measured the plasma soluble endothelin-1 concentrations by a sandwich enzyme immunoassay, and measured oxidative stress as determined by the lipid peroxide byproduct malondialdehyde. Histologic staining and nuclear factor-κB activation determined by electrophoretic mobility shift assay of the amputated vessels were examined. Histologic staining revealed that severe arteriosclerosis with atheroma formation in the amputated diabetic arteries was significantly prominent compared with normal controls. Soluble endothelin-1 concentrations and malondialdehyde levels were increased significantly in diabetic amputation patients compared with other groups (p < 0.001). The nuclear factor-κB binding activity in amputated diabetic stump vessels was more prominent compared with healthy vessels without diabetes mellitus. There was a positive correlation between endothelin-1 and malondialdehyde in patients with diabetic amputation (r = 0.46, p = 0.001). These results suggest that elevation of endothelin-1 and lipid peroxide levels is involved in the pathogenesis of diabetic foot amputation. An increase of lipid peroxide and endothelin-1 associated with nuclear factor-κB activation plays an important role in the development of diabetic angiopathies.

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.

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

An emerging link between LIM domain proteins and nuclear receptors.

PubMed

Sala, Stefano; Ampe, Christophe

2018-06-01

Nuclear receptors are ligand-activated transcription factors that partake in several biological processes including development, reproduction and metabolism. Over the last decade, evidence has accumulated that group 2, 3 and 4 LIM domain proteins, primarily known for their roles in actin cytoskeleton organization, also partake in gene transcription regulation. They shuttle between the cytoplasm and the nucleus, amongst other as a consequence of triggering cells with ligands of nuclear receptors. LIM domain proteins act as important coregulators of nuclear receptor-mediated gene transcription, in which they can either function as coactivators or corepressors. In establishing interactions with nuclear receptors, the LIM domains are important, yet pleiotropy of LIM domain proteins and nuclear receptors frequently occurs. LIM domain protein-nuclear receptor complexes function in diverse physiological processes. Their association is, however, often linked to diseases including cancer.

Nuclear Fabrication Consortium

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

Levesque, Stephen

2013-04-05

This report summarizes the activities undertaken by EWI while under contract from the Department of Energy (DOE) Office of Nuclear Energy (NE) for the management and operation of the Nuclear Fabrication Consortium (NFC). The NFC was established by EWI to independently develop, evaluate, and deploy fabrication approaches and data that support the re-establishment of the U.S. nuclear industry: ensuring that the supply chain will be competitive on a global stage, enabling more cost-effective and reliable nuclear power in a carbon constrained environment. The NFC provided a forum for member original equipment manufactures (OEM), fabricators, manufacturers, and materials suppliers to effectivelymore » engage with each other and rebuild the capacity of this supply chain by : Identifying and removing impediments to the implementation of new construction and fabrication techniques and approaches for nuclear equipment, including system components and nuclear plants. Providing and facilitating detailed scientific-based studies on new approaches and technologies that will have positive impacts on the cost of building of nuclear plants. Analyzing and disseminating information about future nuclear fabrication technologies and how they could impact the North American and the International Nuclear Marketplace. Facilitating dialog and initiate alignment among fabricators, owners, trade associations, and government agencies. Supporting industry in helping to create a larger qualified nuclear supplier network. Acting as an unbiased technology resource to evaluate, develop, and demonstrate new manufacturing technologies. Creating welder and inspector training programs to help enable the necessary workforce for the upcoming construction work. Serving as a focal point for technology, policy, and politically interested parties to share ideas and concepts associated with fabrication across the nuclear industry. The report the objectives and summaries of the Nuclear Fabrication

The line-emitting gas in active galaxies - A probe of the nuclear engine

NASA Technical Reports Server (NTRS)

Veilleux, Sylvain

1993-01-01

This paper reviews some of the basic questions regarding the structure of the engine powering active galactic nuclei (AGN), the nature of the interaction between the AGN and the host galaxy, and the origin and evolution of AGN. The study of the dynamics and physical characteristics of the line-emitting gas in these objects has proven fruitful in addressing many of these issues. Recent advances in optical and infrared detector technology combined with the development of superior ground-based instruments have produced efficient new tools for the study of the line-emitting gas on nuclear and Galactic scales. Programs which take advantage of two of these new techniques, Fabry-Perot imaging spectroscopy and infrared spectroscopy, are described in this paper. The origin of nuclear activity in galaxies is also addressed in a third project which aims at determining the nature of luminous infrared galaxies.

Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization.

PubMed

Pinarbasi, Emile S; Cağatay, Tolga; Fung, Ho Yee Joyce; Li, Ying C; Chook, Yuh Min; Thomas, Philip J

2018-05-04

ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized by the redistribution of the RNA binding protein TDP-43 in affected neurons: from predominantly nuclear to aggregated in the cytosol. However, the determinants of TDP-43 localization and the cellular insults that promote redistribution are incompletely understood. Here, we show that the putative Nuclear Export Signal (NES) is not required for nuclear egress of TDP-43. Moreover, when the TDP-43 domain which contains the putative NES is fused to a reporter protein, YFP, the presence of the NES is not sufficient to mediate nuclear exclusion of the fusion protein. We find that the previously studied "∆NES" mutant, in which conserved hydrophobic residues are mutated to alanines, disrupts both solubility and splicing function. We further show that nuclear export of TDP-43 is independent of the exportin XPO1. Finally, we provide evidence that nuclear egress of TDP-43 is size dependent; nuclear export of dTomato TDP-43 is significantly impaired compared to Flag TDP-43. Together, these results suggest nuclear export of TDP-43 is predominantly driven by passive diffusion.

Applications of nuclear physics

NASA Astrophysics Data System (ADS)

Hayes, A. C.

2017-02-01

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Applications of nuclear physics

DOE PAGES

Hayes-Sterbenz, Anna Catherine

2017-01-10

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applicationsmore » of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.« less

Applications of nuclear physics.

PubMed

Hayes, A C

2017-02-01

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applications of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.

Applications of nuclear physics

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

Hayes-Sterbenz, Anna Catherine

Today the applications of nuclear physics span a very broad range of topics and fields. This review discusses a number of aspects of these applications, including selected topics and concepts in nuclear reactor physics, nuclear fusion, nuclear non-proliferation, nuclear-geophysics, and nuclear medicine. The review begins with a historic summary of the early years in applied nuclear physics, with an emphasis on the huge developments that took place around the time of World War II, and that underlie the physics involved in designs of nuclear explosions, controlled nuclear energy, and nuclear fusion. The review then moves to focus on modern applicationsmore » of these concepts, including the basic concepts and diagnostics developed for the forensics of nuclear explosions, the nuclear diagnostics at the National Ignition Facility, nuclear reactor safeguards, and the detection of nuclear material production and trafficking. The review also summarizes recent developments in nuclear geophysics and nuclear medicine. The nuclear geophysics areas discussed include geo-chronology, nuclear logging for industry, the Oklo reactor, and geo-neutrinos. The section on nuclear medicine summarizes the critical advances in nuclear imaging, including PET and SPECT imaging, targeted radionuclide therapy, and the nuclear physics of medical isotope production. Lastly, each subfield discussed requires a review article unto itself, which is not the intention of the current review; rather, the current review is intended for readers who wish to get a broad understanding of applied nuclear physics.« less

Active Interrogation using Photofission Technique for Nuclear Materials Control and Accountability

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

Yang, Haori

2016-03-31

Innovative systems with increased sensitivity and resolution are in great demand to detect diversion and to prevent misuse in support of nuclear materials management for the U.S. fuel cycle. Nuclear fission is the most important multiplicative process involved in non-destructive active interrogation. This process produces the most easily recognizable signature for nuclear materials. In addition to thermal or high-energy neutrons, high-energy gamma rays can also excite a nucleus and cause fission through a process known as photofission. Electron linear accelerators (linacs) are widely used as the interrogating photon sources for inspection methods involving photofission technique. After photofission reactions, prompt signalsmore » are much stronger than the delayed signals, but it is difficult to quantify them in practical measurements. Delayed signals are easily distinguishable from the interrogating radiation. Linac-based, advanced inspection techniques utilizing the delayed signals after photofission have been extensively studied for homeland security applications. Previous research also showed that a unique delayed gamma ray energy spectrum exists for each fissionable isotope. In this work, high-energy delayed γ-rays were demonstrated to be signatures for detection, identification, and quantification of special nuclear materials. Such γ-rays were measured in between linac pulses using independent data acquisition systems. A list-mode system was developed to measure low-energy delayed γ-rays after irradiation. Photofission product yields of 238U and 239Pu were determined based on the measured delayed γ-ray spectra. The differential yields of delayed γ-rays were also proven to be able to discriminate nuclear from non-nuclear materials. The measurement outcomes were compared with Monte Carlo simulation results. It was demonstrated that the current available codes have capabilities and limitations in the simulation of photofission process. A two-fold approach

Estetrol, a Fetal Selective Estrogen Receptor Modulator, Acts on the Vagina of Mice through Nuclear Estrogen Receptor α Activation.

PubMed

Benoit, Thibaut; Valera, Marie-Cecile; Fontaine, Coralie; Buscato, Melissa; Lenfant, Francoise; Raymond-Letron, Isabelle; Tremollieres, Florence; Soulie, Michel; Foidart, Jean-Michel; Game, Xavier; Arnal, Jean-Francois

2017-11-01

The genitourinary syndrome of menopause has a negative impact on quality of life of postmenopausal women. The treatment of vulvovaginal atrophy includes administration of estrogens. However, oral estrogen treatment is controversial because of its potential risks on venous thrombosis and breast cancer. Estetrol (E4) is a natural estrogen synthesized exclusively during pregnancy by the human fetal liver and initially considered as a weak estrogen. However, E4 was recently evaluated in phase 1 to 2 clinical studies and found to act as an oral contraceptive in combination with a progestin, without increasing the level of coagulation factors. We recently showed that E4 stimulates uterine epithelial proliferation through nuclear estrogen receptor (ER) α, but failed to elicit endothelial responses. Herein, we first evaluated the morphological and functional impacts of E4 on the vagina of ovariectomized mice, and we determined the molecular mechanism mediating these effects. Vaginal epithelial proliferation and lubrication after stimulation were found to increase after E4 chronic treatment. Using a combination of pharmacological and genetic approaches, we demonstrated that these E4 effects on the vagina are mediated by nuclear ERα activation. Altogether, we demonstrate that the selective activation of nuclear ERα is both necessary and sufficient to elicit functional and structural effects on the vagina, and therefore E4 appears promising as a therapeutic option to improve vulvovaginal atrophy. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

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.

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

Controlling nuclear JAKs and STATs for specific gene activation by IFN{gamma}

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

Noon-Song, Ezra N.; Ahmed, Chulbul M.; Dabelic, Rea

2011-07-08

Highlights: {yields} Gamma interferon (IFN{gamma}) and its receptor subunit, IFNGR1, interact with the promoter region of IFN{gamma}-associated genes along with transcription factor STAT1{alpha}. {yields} We show that activated Janus kinases pJAK2 and pJAK1 also associate with IFNGR1 in the nucleus. {yields} The activated Janus kinases are responsible for phosphorylation of tyrosine 41 on histone H3, an important epigenetic event for specific gene activation. -- Abstract: We previously showed that gamma interferon (IFN{gamma}) and its receptor subunit, IFNGR1, interacted with the promoter region of IFN{gamma}-activated genes along with transcription factor STAT1{alpha}. Recent studies have suggested that activated Janus kinases pJAK2 andmore » pJAK1 also played a role in gene activation by phosphorylation of histone H3 on tyrosine 41. This study addresses the question of the role of activated JAKs in specific gene activation by IFN{gamma}. We carried out chromatin immunoprecipitation (ChIP) followed by PCR in IFN{gamma} treated WISH cells and showed association of pJAK1, pJAK2, IFNGR1, and STAT1 on the same DNA sequence of the IRF-1 gene promoter. The {beta}-actin gene, which is not activated by IFN{gamma}, did not show this association. The movement of activated JAK to the nucleus and the IRF-1 promoter was confirmed by the combination of nuclear fractionation, confocal microscopy and DNA precipitation analysis using the biotinylated GAS promoter. Activated JAKs in the nucleus was associated with phosphorylated tyrosine 41 on histone H3 in the region of the GAS promoter. Unphosphorylated JAK2 was found to be constitutively present in the nucleus and was capable of undergoing activation in IFN{gamma} treated cells, most likely via nuclear IFNGR1. Association of pJAK2 and IFNGR1 with histone H3 in IFN{gamma} treated cells was demonstrated by histone H3 immunoprecipitation. Unphosphorylated STAT1 protein was associated with histone H3 of untreated cells. IFN

Measurement of 131I activity in thyroid of nuclear medical staff and internal dose assessment in a Polish nuclear medical hospital.

PubMed

Brudecki, K; Kowalska, A; Zagrodzki, P; Szczodry, A; Mroz, T; Janowski, P; Mietelski, J W

2017-03-01

This paper presents results of 131 I thyroid activity measurements in 30 members of the nuclear medicine personnel of the Department of Endocrinology and Nuclear Medicine Holy Cross Cancer Centre in Kielce, Poland. A whole-body spectrometer equipped with two semiconductor gamma radiation detectors served as the basic research instrument. In ten out of 30 examined staff members, the determined 131 I activity was found to be above the detection limit (DL = 5 Bq of 131 I in the thyroid). The measured activities ranged from (5 ± 2) Bq to (217 ± 56) Bq. The highest activities in thyroids were detected for technical and cleaning personnel, whereas the lowest values were recorded for medical doctors. Having measured the activities, an attempt has been made to estimate the corresponding annual effective doses, which were found to range from 0.02 to 0.8 mSv. The highest annual equivalent doses have been found for thyroid, ranging from 0.4 to 15.4 mSv, detected for a cleaner and a technician, respectively. The maximum estimated effective dose corresponds to 32% of the annual background dose in Poland, and to circa 4% of the annual limit for the effective dose due to occupational exposure of 20 mSv per year, which is in compliance with the value recommended by the International Commission on Radiological Protection.

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

Cooperative activity of GABP with PU.1 or C/EBPε regulates lamin B receptor gene expression, implicating their roles in granulocyte nuclear maturation1

PubMed Central

Malu, Krishnakumar; Garhwal, Rahul; Pelletier, Margery G. H.; Gotur, Deepali; Halene, Stephanie; Zwerger, Monika; Yang, Zhong-Fa; Rosmarin, Alan G.; Gaines, Peter

2016-01-01

Nuclear segmentation is a hallmark feature of mammalian neutrophil differentiation, but the mechanisms that control this process are poorly understood. Gene expression in maturing neutrophils requires combinatorial actions of lineage-restricted and more widely expressed transcriptional regulators. Examples include interactions of the widely expressed ETS transcription factor, GA-binding protein (GABP), with the relatively lineage-restricted ETS factor, PU.1, and with CCAAT enhancer binding proteins, C/EBPα and C/EBPε. Whether such cooperative interactions between these transcription factors also regulate the expression of genes encoding proteins that control nuclear segmentation is unclear. We investigated the roles of ETS and C/EBP family transcription factors in regulating the gene encoding the lamin B receptor (LBR), an inner nuclear membrane protein whose expression is required for neutrophil nuclear segmentation. Although C/EBPε was previously shown to bind the Lbr promoter, surprisingly, we found that neutrophils derived from Cebpe null mice exhibited normal Lbr gene and protein expression. Instead, GABP provided transcriptional activation through the Lbr promoter in the absence of C/EBPε, and activities supported by GABP were greatly enhanced by either C/EBPε or PU.1. Both GABP and PU.1 bound Ets sites in the Lbr promoter in vitro, and in vivo within both early myeloid progenitors and differentiating neutrophils. These findings demonstrate that GABP, PU.1, and C/EBPε cooperate to control transcription of the gene encoding LBR, a nuclear envelope protein that is required for the characteristic lobulated morphology of mature neutrophils. PMID:27342846

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

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…

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

The economics of nuclear power

NASA Astrophysics Data System (ADS)

Horst, Ronald L.

We extend economic analysis of the nuclear power industry by developing and employing three tools. They are (1) compilation and unification of operating and accounting data sets for plants and sites, (2) an abstract industry model with major economic agents and features, and (3) a model of nuclear power plant operators. We build a matched data set to combine dissimilar but mutually dependant bodies of information. We match detailed information on the activities and conditions of individual plants to slightly more aggregated financial data. Others have exploited the data separately, but we extend the sets and pool available data sets. The data reveal dramatic changes in the industry over the past thirty years. The 1980s proved unprofitable for the industry. This is evident both in the cost data and in the operator activity data. Productivity then improved dramatically while cost growth stabilized to the point of industry profitability. Relative electricity prices may be rising after nearly two decades of decline. Such demand side trends, together with supply side improvements, suggest a healthy industry. Our microeconomic model of nuclear power plant operators employs a forward-looking component to capture the information set available to decision makers and to model the decision-making process. Our model includes features often overlooked elsewhere, including electricity price equations and liability. Failure to account for changes in electricity price trends perhaps misled earlier scholars, and they attributed to other causes the effects on profits of changing price structures. The model includes potential losses resulting from catastrophic nuclear accidents. Applications include historical simulations and forecasts. Nuclear power involves risk, and accident costs are borne both by plant owners and the public. Authorities regulate the industry and balance conflicting desires for economic gain and safety. We construct an extensible model with regulators, plant

Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

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

Baek, Jong Min; Park, Sun-Hyang; Cheon, Yoon-Hee

Esculetin exerts various biological effects on anti-oxidation, anti-tumors, and anti-inflammation. However, the involvement of esculetin in the bone metabolism process, particularly osteoclast differentiation has not yet been investigated. In the present study, we first confirmed the inhibitory effect of esculetin on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. We then revealed the relationship between esculetin and the expression of osteoclast-specific molecules to elucidate its underlying mechanisms. Esculetin interfered with the expression of c-Fos and nuclear factor of activated T cell c1 (NFATc1) both at the mRNA and protein level with no involvement in osteoclast-associated early signaling pathways, suppressingmore » the expression of various transcription factors exclusively expressed in osteoclasts such as tartrate-resistant acid phosphatase (Trap), osteoclast-associated receptor (Oscar), dendritic cell-specific transmembrane protein (Dcstamp), osteoclast stimulatory transmembrane protein (Ocstamp), cathepsin K, αvβ3 integrin, and calcitonin receptor (Ctr). Additionally, esculetin inhibited the formation of filamentous actin (F-actin) ring-positive osteoclasts during osteoclast differentiation. However, the development of F-actin structures and subsequent bone resorbing activity of mature osteoclasts, which are observed in osteoclast/osteoblast co-culture systems were not affected by esculetin. Taken together, our results indicate for the first time that esculetin inhibits RANKL-mediated osteoclastogenesis via direct suppression of c-Fos and NFATc1 expression and exerts an inhibitory effect on actin ring formation during osteoclastogenesis. - Highlights: • We first investigated the effects of esculetin on osteoclast differentiation and function. • Our data demonstrate for the first time that esculetin can suppress osteoclastogenesis in vitro. • Esculetin acts as an inhibitor of c-Fos and NFATc1 activation

An Analysis Framework for Understanding the Origin of Nuclear Activity in Low-power Radio Galaxies

NASA Astrophysics Data System (ADS)

Lin, Yen-Ting; Huang, Hung-Jin; Chen, Yen-Chi

2018-05-01

Using large samples containing nearly 2300 active galaxies of low radio luminosity (1.4 GHz luminosity between 2 × 1023 and 3 × 1025 W Hz‑1, essentially low-excitation radio galaxies) at z ≲ 0.3, we present a self-contained analysis of the dependence of the nuclear radio activity on both intrinsic and extrinsic properties of galaxies, with the goal of identifying the best predictors of the nuclear radio activity. While confirming the established result that stellar mass must play a key role on the triggering of radio activities, we point out that for the central, most massive galaxies, the radio activity also shows a strong dependence on halo mass, which is not likely due to enhanced interaction rates in denser regions in massive, cluster-scale halos. We thus further investigate the effects of various properties of the intracluster medium (ICM) in massive clusters on the radio activities, employing two standard statistical tools, principle component analysis and logistic regression. It is found that ICM entropy, local cooling time, and pressure are the most effective in predicting the radio activity, pointing to the accretion of gas cooling out of a hot atmosphere to be the likely origin in triggering such activities in galaxies residing in massive dark matter halos. Our analysis framework enables us to logically discern the mechanisms responsible for the radio activity separately for central and satellite galaxies.

Nuclear Safety

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

Silver, E G

This document is a review journal that covers significant developments in the field of nuclear safety. Its scope includes the analysis and control of hazards associated with nuclear energy, operations involving fissionable materials, and the products of nuclear fission and their effects on the environment. Primary emphasis is on safety in reactor design, construction, and operation; however, the safety aspects of the entire fuel cycle, including fuel fabrication, spent-fuel processing, nuclear waste disposal, handling of radioisotopes, and environmental effects of these operations, are also treated.

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

Accuracy and Precision of Radioactivity Quantification in Nuclear Medicine Images

PubMed Central

Frey, Eric C.; Humm, John L.; Ljungberg, Michael

2012-01-01

The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images. PMID:22475429

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

Prognostic and health management of active assets in nuclear power plants

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

Agarwal, Vivek; Lybeck, Nancy; Pham, Binh T.

This study presents the development of diagnostic and prognostic capabilities for active assets in nuclear power plants (NPPs). The research was performed under the Advanced Instrumentation, Information, and Control Technologies Pathway of the Light Water Reactor Sustainability Program. Idaho National Laboratory researched, developed, implemented, and demonstrated diagnostic and prognostic models for generator step-up transformers (GSUs). The Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software developed by the Electric Power Research Institute was used to perform diagnosis and prognosis. As part of the research activity, Idaho National Laboratory implemented 22 GSU diagnostic models in the Asset Fault Signature Database and twomore » wellestablished GSU prognostic models for the paper winding insulation in the Remaining Useful Life Database of the FW-PHM Suite. The implemented models along with a simulated fault data stream were used to evaluate the diagnostic and prognostic capabilities of the FW-PHM Suite. Knowledge of the operating condition of plant asset gained from diagnosis and prognosis is critical for the safe, productive, and economical long-term operation of the current fleet of NPPs. This research addresses some of the gaps in the current state of technology development and enables effective application of diagnostics and prognostics to nuclear plant assets.« less

Prognostic and health management of active assets in nuclear power plants

DOE PAGES

Agarwal, Vivek; Lybeck, Nancy; Pham, Binh T.; ...

2015-06-04

This study presents the development of diagnostic and prognostic capabilities for active assets in nuclear power plants (NPPs). The research was performed under the Advanced Instrumentation, Information, and Control Technologies Pathway of the Light Water Reactor Sustainability Program. Idaho National Laboratory researched, developed, implemented, and demonstrated diagnostic and prognostic models for generator step-up transformers (GSUs). The Fleet-Wide Prognostic and Health Management (FW-PHM) Suite software developed by the Electric Power Research Institute was used to perform diagnosis and prognosis. As part of the research activity, Idaho National Laboratory implemented 22 GSU diagnostic models in the Asset Fault Signature Database and twomore » wellestablished GSU prognostic models for the paper winding insulation in the Remaining Useful Life Database of the FW-PHM Suite. The implemented models along with a simulated fault data stream were used to evaluate the diagnostic and prognostic capabilities of the FW-PHM Suite. Knowledge of the operating condition of plant asset gained from diagnosis and prognosis is critical for the safe, productive, and economical long-term operation of the current fleet of NPPs. This research addresses some of the gaps in the current state of technology development and enables effective application of diagnostics and prognostics to nuclear plant assets.« less

Importance of nuclear localization for the apoptosis-induced activity of a fungal galectin AAL (Agrocybe aegerita lectin)

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

Liang, Yi; Feng, Lei; Tong, Xin

2009-08-28

Agrocybe aegerita lectin (AAL) was identified previously in our group as a novel galectin from medicinal fungi Agrocybe aegerita, and has been shown to effectively induce cancer cell cycle arrest and apoptosis in vitro and tumor regression in vivo. Here, AAL was observed to translocate into the HeLa cell nucleus and induce cell apoptosis when it was predominantly in the nucleus. The N-terminus and C-terminus of AAL were required for nuclear localization. Site mutated proteins were generated based on AAL structure. Dimer interface mutant I25G, carbohydrate recognition domain (CRD) mutant R63H, and loop region mutant L33A could not enter themore » nucleus and lost the ability to induce apoptosis. CRD mutant H59Q and loop region mutant I144G maintained nuclear localization activity, and H59Q retained residual bioability but I144G had no activity, indicating that nuclear localization is important but not sufficient for AAL to become apoptotically active. Our findings provide a novel antitumor mechanism of fungal galectin.« less

AGN POPULATION IN HICKSON COMPACT GROUPS. I. DATA AND NUCLEAR ACTIVITY CLASSIFICATION

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

MartInez, M. A.; Del Olmo, A.; Perea, J.

2010-03-15

We have conducted a new spectroscopic survey to characterize the nature of nuclear activity in Hickson compact group (HCG) galaxies and establish its frequency. We have obtained new intermediate-resolution optical spectroscopy for 200 member galaxies and corrected for underlying stellar population contamination using galaxy templates. Spectra for 11 additional galaxies have been acquired from the ESO and 6dF public archives, and emission-line ratios have been taken from the literature for 59 more galaxies. Here we present the results of our classification of the nuclear activity for 270 member galaxies, which belong to a well-defined sample of 64 HCGs. We foundmore » a large fraction of galaxies, 63%, with emission lines. Using standard diagnostic diagrams, 45% of the emission-line galaxies were classified as pure active galactic nuclei (AGNs), 23% as Transition Objects (TOs), and 32% as star-forming nuclei (SFNs). In the HCGs, the AGN activity appears as the most frequent activity type. Adopting the interpretation that in TOs a low-luminosity AGN coexists with circumnuclear star formation, the fraction of galaxies with an AGN could rise to 42% of the whole sample. The low frequency (20%) of SFNs confirms that there is no star formation enhancement in HCGs. After extinction correction, we found a median AGN H{alpha} luminosity of 7.1 x 10{sup 39} erg s{sup -1}, which implies that AGNs in HCG have a characteristically low luminosity. This result added to the fact that there is an almost complete absence of broad-line AGNs in compact groups (CGs) as found by MartInez et al. and corroborated in this study for HCGs, is consistent with very few gas left in these galaxies. In general, therefore, what may characterize the level of activity in CGs is a severe deficiency of gas.« less

Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

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

Reimers, Kerstin; Buchholz, Katja; Werchau, Hermann

2005-01-20

Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cellsmore » revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.« less

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.

Amounts and activity concentrations of radioactive wastes from the cleanup of large areas contaminated in nuclear accidents

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

Lehto, J.; Ikaeheimonen, T.K.; Salbu, B.

The fallout from a major nuclear accident at a nuclear plant may result in a wide-scale contamination of the environment. Cleanup of contaminated areas is of special importance if these areas are populated or cultivated. All cleanup measures generate high amounts of radioactive waste, which have to be treated and disposed of in a safe manner. Scenarios assessing the amounts and activity concentrations of radioactive wastes for various cleanup measures after severe nuclear accidents have been worked out for urban, forest and agricultural areas. These scenarios are based on contamination levels and ares of contaminated lands from a model accident,more » which simulates a worst case accident at a nuclear power plant. Amounts and activity concentrations of cleanup wastes are not only dependent on the contamination levels and areas of affected lands, but also on the type of deposition, wet or dry, on the time between the deposition and the cleanup work, on the season, at which the deposition took place, and finally on the level of cleanup work. In this study practically all types of cleanup wastes were considered, whether or not the corresponding cleanup measures are cost-effective or justified. All cleanup measures are shown to create large amounts of radioactive wastes, but the amounts, as well as the activity concentrations vary widely from case to case.« less

An historical collection of papers on nuclear thermal propulsion

NASA Astrophysics Data System (ADS)

The present volume of historical papers on nuclear thermal propulsion (NTP) encompasses NTP technology development regarding solid-core NTP technology, advanced concepts from the early years of NTP research, and recent activities in the field. Specific issues addressed include NERVA rocket-engine technology, the development of nuclear rocket propulsion at Los Alamos, fuel-element development, reactor testing for the Rover program, and an overview of NTP concepts and research emphasizing two decades of NASA research. Also addressed are the development of the 'nuclear light bulb' closed-cycle gas core and a demonstration of a fissioning UF6 gas in an argon vortex. The recent developments reviewed include the application of NTP to NASA's Lunar Space Transportation System, the use of NTP for the Space Exploration Initiative, and the development of nuclear rocket engines in the former Soviet Union.

Role of nuclear bodies in apoptosis signalling.

PubMed

Krieghoff-Henning, Eva; Hofmann, Thomas G

2008-11-01

Promyelocytic leukemia nuclear bodies (PML NBs) are dynamic macromolecular multiprotein complexes that recruit and release a plethora of proteins. A considerable number of PML NB components play vital roles in apoptosis, senescence regulation and tumour suppression. The molecular basis by which PML NBs control these cellular responses is still just beginning to be understood. In addition to PML itself, numerous further tumour suppressors including transcriptional regulator p53, acetyl transferase CBP (CREB binding protein) and protein kinase HIPK2 (homeodomain interacting protein kinase 2) are recruited to PML NBs in response to genotoxic stress or oncogenic transformation and drive the senescence and apoptosis response by regulating p53 activity. Moreover, in response to death-receptor activation, PML NBs may act as nuclear depots that release apoptotic factors, such as the FLASH (FLICE-associated huge) protein, to amplify the death signal. PML NBs are also associated with other nuclear domains including Cajal bodies and nucleoli and share apoptotic regulators with these domains, implying crosstalk between NBs in apoptosis regulation. In conclusion, PML NBs appear to regulate cell death decisions through different, pathway-specific molecular mechanisms.

Nursing education and the nuclear age

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

McKay, S.

As reflected in the nursing literature, nurses have only recently begun discussing professional responsibilities for avoidance of nuclear war. The literature of the 1950s and 1960s focused on issues of civil defense. The 1970s were mostly silent, but with the onset of the 1980s a few articles identified the need for the nursing profession to recognize the importance of nuclear war prevention. The responsibility of nursing education for including content about nuclear issues has not been discussed in the professional literature. The author surveyed baccalaureate programs of nursing education to determine whether this lack of discussion was reflected in nursingmore » curricula. Responses indicated that the literature does not adequately reflect the level of activity and interest occurring within nursing education about nuclear issues. Nevertheless, because there is so little discussion in the professional literature, an implicit message is sent that nuclear issues are not of importance and that nurses should not openly address them.24 references.« less

Nuclear physics experiments with low cost instrumentation

NASA Astrophysics Data System (ADS)

Oliveira Bastos, Rodrigo; Adelar Boff, Cleber; Melquiades, Fábio Luiz

2016-11-01

One of the difficulties in modern physics teaching is the limited availability of experimental activities. This is particularly true for teaching nuclear physics in high school or college. The activities suggested in the literature generally symbolise real phenomenon, using simulations. It happens because the experimental practices mostly include some kind of expensive radiation detector and an ionising radiation source that requires special care for handling and storage, being subject to a highly bureaucratic regulation in some countries. This study overcomes these difficulties and proposes three nuclear physics experiments using a low-cost ion chamber which construction is explained: the measurement of 222Rn progeny collected from the indoor air; the measurement of the range of alpha particles emitted by the 232Th progeny, present in lantern mantles and in thoriated welding rods, and by the air filter containing 222Rn progeny; and the measurement of 220Rn half-life collected from the emanation of the lantern mantles. This paper presents the experimental procedures and the expected results, indicating that the experiments may provide support for nuclear physics classes. These practices may outreach wide access to either college or high-school didactic laboratories, and the apparatus has the potential for the development of new teaching activities for nuclear physics.

NCRP Program Area Committee 3: Nuclear and Radiological Security and Safety [Update on the Ncrp Program Area Committee 3 Activities: Nuclear And Radiological Security and Safety

DOE PAGES

Ansari, Armin; Buddemeier, Brooke

2018-02-01

The National Council on Radiation Protection and Measurements (NCRP) Program Area Committee (PAC) 3 covers the broad subject of nuclear and radiological security and safety and provides guidance and recommendations for response to nuclear and radiological incidents of both an accidental and deliberate nature. In 2017, PAC 3 Scientific Committee 3-1 completed the development of Guidance for Emergency Responder Dosimetry, and began development of a companion commentary on operational aspects of that guidance. PAC 3 members also organized the technical program for the 2017 Annual Meeting of the NCRP on “Assessment of National Efforts in Emergency Preparedness for Nuclear Terrorism:more » Is There a Need for Realignment to Close Remaining Gaps.” Based on discussions and presentations at the annual meeting, PAC 3 is working to develop a commentary on the subject that could serve as a roadmap for focusing our national efforts on the most pressing needs for preparing the nation for nuclear and radiological emergencies. PAC 3 is also engaged in active discussions, exploring the landscape of priority issues for its future activities. Lastly, an important consideration in this discussion is the extent of NCRP’s present and potential future resources to support the work of its scientific committees.« less

NCRP Program Area Committee 3: Nuclear and Radiological Security and Safety [Update on the Ncrp Program Area Committee 3 Activities: Nuclear And Radiological Security and Safety

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

Ansari, Armin; Buddemeier, Brooke

The National Council on Radiation Protection and Measurements (NCRP) Program Area Committee (PAC) 3 covers the broad subject of nuclear and radiological security and safety and provides guidance and recommendations for response to nuclear and radiological incidents of both an accidental and deliberate nature. In 2017, PAC 3 Scientific Committee 3-1 completed the development of Guidance for Emergency Responder Dosimetry, and began development of a companion commentary on operational aspects of that guidance. PAC 3 members also organized the technical program for the 2017 Annual Meeting of the NCRP on “Assessment of National Efforts in Emergency Preparedness for Nuclear Terrorism:more » Is There a Need for Realignment to Close Remaining Gaps.” Based on discussions and presentations at the annual meeting, PAC 3 is working to develop a commentary on the subject that could serve as a roadmap for focusing our national efforts on the most pressing needs for preparing the nation for nuclear and radiological emergencies. PAC 3 is also engaged in active discussions, exploring the landscape of priority issues for its future activities. Lastly, an important consideration in this discussion is the extent of NCRP’s present and potential future resources to support the work of its scientific committees.« less

Integrative Curriculum Development in Nuclear Education and Research Vertical Enhancement Program

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

Egarievwe, Stephen U.; Jow, Julius O.; Edwards, Matthew E.

Using a vertical education enhancement model, a Nuclear Education and Research Vertical Enhancement (NERVE) program was developed. The NERVE program is aimed at developing nuclear engineering education and research to 1) enhance skilled workforce development in disciplines relevant to nuclear power, national security and medical physics, and 2) increase the number of students and faculty from underrepresented groups (women and minorities) in fields related to the nuclear industry. The program uses multi-track training activities that vertically cut across the several education domains: undergraduate degree programs, graduate schools, and post-doctoral training. In this paper, we present the results of an integrativemore » curriculum development in the NERVE program. The curriculum development began with nuclear content infusion into existing science, engineering and technology courses. The second step involved the development of nuclear engineering courses: 1) Introduction to Nuclear Engineering, 2) Nuclear Engineering I, and 2) Nuclear Engineering II. The third step is the establishment of nuclear engineering concentrations in two engineering degree programs: 1) electrical engineering, and 2) mechanical engineering. A major outcome of the NERVE program is a collaborative infrastructure that uses laboratory work, internships at nuclear facilities, on-campus research, and mentoring in collaboration with industry and government partners to provide hands-on training for students. The major activities of the research and education collaborations include: - One-week spring training workshop at Brookhaven National Laboratory: The one-week training and workshop is used to enhance research collaborations and train faculty and students on user facilities/equipment at Brookhaven National Laboratory, and for summer research internships. Participants included students, faculty members at Alabama A and M University and research collaborators at BNL. The activities include 1

Nuclear Thermal Propulsion (NTP) Development Activities at the NASA Marshall Space Flight Center - 2006 Accomplishments

NASA Technical Reports Server (NTRS)

Ballard, Richard O.

2007-01-01

In 2005-06, the Prometheus program funded a number of tasks at the NASA-Marshall Space Flight Center (MSFC) to support development of a Nuclear Thermal Propulsion (NTP) system for future manned exploration missions. These tasks include the following: 1. NTP Design Develop Test & Evaluate (DDT&E) Planning 2. NTP Mission & Systems Analysis / Stage Concepts & Engine Requirements 3. NTP Engine System Trade Space Analysis and Studies 4. NTP Engine Ground Test Facility Assessment 5. Non-Nuclear Environmental Simulator (NTREES) 6. Non-Nuclear Materials Fabrication & Evaluation 7. Multi-Physics TCA Modeling. This presentation is a overview of these tasks and their accomplishments

Improvements to the FATOLA computer program including added actively controlled landing gear subroutines

NASA Technical Reports Server (NTRS)

Mall, G. H.

1983-01-01

Modifications to a multi-degree-of-freedom flexible aircraft take-off and landing analysis (FATOLA) computer program, including a provision for actively controlled landing gears to expand the programs simulation capabilities, are presented. Supplemental instructions for preparation of data and for use of the modified program are included.

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.

Hantaan virus nucleocapsid protein binds to importin alpha proteins and inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappa B.

PubMed

Taylor, Shannon L; Frias-Staheli, Natalia; García-Sastre, Adolfo; Schmaljohn, Connie S

2009-02-01

Hantaviruses such as Hantaan virus (HTNV) and Andes virus cause two human diseases, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. For both, disease pathogenesis is thought to be immunologically mediated and there have been numerous reports of patients with elevated levels of proinflammatory and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), in their sera. Multiple viruses have developed evasion strategies to circumvent the host cell inflammatory process, with one of the most prevalent being the disruption of nuclear factor kappa B (NF-kappaB) activation. We hypothesized that hantaviruses might also moderate host inflammation by interfering with this pathway. We report here that the nucleocapsid (N) protein of HTNV was able to inhibit TNF-alpha-induced activation of NF-kappaB, as measured by a reporter assay, and the activation of endogenous p65, an NF-kappaB subunit. Surprisingly, there was no defect in the degradation of the inhibitor of NF-kappaB (IkappaB) protein, nor was there any alteration in the level of p65 expression in HTNV N-expressing cells. However, immunofluorescence antibody staining demonstrated that cells expressing HTNV N protein and a green fluorescent protein-p65 fusion had limited p65 nuclear translocation. Furthermore, we were able to detect an interaction between HTNV N protein and importin alpha, a nuclear import molecule responsible for shuttling NF-kappaB to the nucleus. Collectively, our data suggest that HTNV N protein can sequester NF-kappaB in the cytoplasm, thus inhibiting NF-kappaB activity. These findings, which were obtained using cells transfected with cDNA representing the HTNV N gene, were confirmed using HTNV-infected cells.

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

Activities report in nuclear physics and particle acceleration

NASA Astrophysics Data System (ADS)

Jansen, J. F. W.; Demeijer, R. J.

1984-04-01

Research on nuclear resonances; charge transfer; breakup of light and heavy ions; reaction mechanisms of heavy ion collisions; high-spin states; and fundamental symmetries in weak interactions are outlined. Group theoretical methods applied to supersymmetries; phenomenological description of rotation-vibration coupling; a microscopic theory of collective variables; the binding energy of hydrogen adsorbed on stepped platinium; and single electron capture are discussed. Isotopes for nuclear medicine, for off-line nuclear spectroscopy work, and for the study of hyperfine interactions were produced.

Strontium-90 activity concentration in soil samples from the exclusion zone of the Fukushima daiichi nuclear power plant

NASA Astrophysics Data System (ADS)

Sahoo, Sarata Kumar; Kavasi, Norbert; Sorimachi, Atsuyuki; Arae, Hideki; Tokonami, Shinji; Mietelski, Jerzy Wojciech; Łokas, Edyta; Yoshida, Satoshi

2016-04-01

The radioactive fission product 90Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing 90Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure 90Sr activity concentration using liquid scintillation counting. 137Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with 90Sr. The 90Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg-1 while the 137Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg-1. The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of 134Cs. However, 90Sr contamination was not confirmed in all samples although detectable amounts of 90Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between 90Sr and 137Cs activity concentrations provides a potentially powerful tool to discriminate background 90Sr level from its Fukushima contribution.

Strontium-90 activity concentration in soil samples from the exclusion zone of the Fukushima daiichi nuclear power plant.

PubMed

Sahoo, Sarata Kumar; Kavasi, Norbert; Sorimachi, Atsuyuki; Arae, Hideki; Tokonami, Shinji; Mietelski, Jerzy Wojciech; Łokas, Edyta; Yoshida, Satoshi

2016-04-06

The radioactive fission product (90)Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing (90)Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure (90)Sr activity concentration using liquid scintillation counting. (137)Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with (90)Sr. The (90)Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg(-1) while the (137)Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg(-1). The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of (134)Cs. However, (90)Sr contamination was not confirmed in all samples although detectable amounts of (90)Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between (90)Sr and (137)Cs activity concentrations provides a potentially powerful tool to discriminate background (90)Sr level from its Fukushima contribution.

Strontium-90 activity concentration in soil samples from the exclusion zone of the Fukushima daiichi nuclear power plant

PubMed Central

Sahoo, Sarata Kumar; Kavasi, Norbert; Sorimachi, Atsuyuki; Arae, Hideki; Tokonami, Shinji; Mietelski, Jerzy Wojciech; Łokas, Edyta; Yoshida, Satoshi

2016-01-01

The radioactive fission product 90Sr has a long biological half-life (˜18 y) in the human body. Due to its chemical similarity to calcium it accumulates in bones and irradiates the bone marrow, causing its high radio-toxicity. Assessing 90Sr is therefore extremely important in case of a nuclear disaster. In this work 16 soil samples were collected from the exclusion zone (<30 km) of the earthquake-damaged Fukushima Daiichi nuclear power plant, to measure 90Sr activity concentration using liquid scintillation counting. 137Cs activity concentration was also measured with gamma-spectroscopy in order to investigate correlation with 90Sr. The 90Sr activity concentrations ranged from 3.0 ± 0.3 to 23.3 ± 1.5 Bq kg−1 while the 137Cs from 0.7 ± 0.1 to 110.8 ± 0.3 kBq kg−1. The fact that radioactive contamination originated from the Fukushima nuclear accident was obvious due to the presence of 134Cs. However, 90Sr contamination was not confirmed in all samples although detectable amounts of 90Sr can be expected in Japanese soils, as a background, stemming from global fallout due to the atmospheric nuclear weapon tests. Correlation analysis between 90Sr and 137Cs activity concentrations provides a potentially powerful tool to discriminate background 90Sr level from its Fukushima contribution. PMID:27048779

Inhibition of Nuclear Transcription Factor-κB and Activation of Peroxisome Proliferator-Activated Receptors in HepG2 Cells by Cucurbitane-Type Triterpene Glycosides from Momordica charantia

PubMed Central

Nhiem, Nguyen Xuan; Yen, Pham Hai; Ngan, Nguyen Thi Thanh; Quang, Tran Hong; Kiem, Phan Van; Minh, Chau Van; Tai, Bui Huu; Cuong, Nguyen Xuan; Song, Seok Bean

2012-01-01

Abstract Momordica charantia: is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1–17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC50) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC50=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation. PMID:22248180

Nuclear factor-kappaB activation and postischemic inflammation are suppressed in CD36-null mice after middle cerebral artery occlusion.

PubMed

Kunz, Alexander; Abe, Takato; Hochrainer, Karin; Shimamura, Munehisa; Anrather, Josef; Racchumi, Gianfranco; Zhou, Ping; Iadecola, Costantino

2008-02-13

CD36, a class-B scavenger receptor involved in multiple functions, including inflammatory signaling, may also contribute to ischemic brain injury through yet unidentified mechanisms. We investigated whether CD36 participates in the molecular events underlying the inflammatory reaction that accompanies cerebral ischemia and may contribute to the tissue damage. We found that activation of nuclear factor-kappaB, a transcription factor that coordinates postischemic gene expression, is attenuated in CD36-null mice subjected to middle cerebral artery occlusion. The infiltration of neutrophils and the glial reaction induced by cerebral ischemia were suppressed. Treatment with an inhibitor of inducible nitric oxide synthase, an enzyme that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD36 nulls. In contrast to cerebral ischemia, the molecular and cellular inflammatory changes induced by intracerebroventricular injection of interleukin-1beta were not attenuated in CD36-null mice. The findings unveil a novel role of CD36 in early molecular events leading to nuclear factor-kappaB activation and postischemic inflammation. Inhibition of CD36 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

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.

GKTC ACTIVITIES TO PROVIDE NUCLEAR MATERIAL PHYSICAL PROTECTION, CONTROL AND ACCOUNTING TRAINING FOR 2011-2012

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

Romanova, Olena; Gavrilyuk, Victor I.; Kirischuk, Volodymyr

2011-10-01

The GKTC was created at the Kyiv Institute of Nuclear Research as a result of collaborative efforts between the United States and Ukraine. The GKTC has been designated by the Ukrainian Government to provide the MPC&A training and methodological assistance to nuclear facilities and nuclear specialists. In 2010 the GKTC has conducted the planned assessment of training needs of Ukrainian MPC&A specialists. The objective of this work is to acquire the detailed information about the number of MPC&A specialists and guard personnel, who in the coming years should receive the further advanced training. As a result of the performed trainingmore » needs evaluation the GKTC has determined that in the coming years a number of new training courses need to be developed. Some training courses are already in the process of development. Also taking into account the specific of activity on the guarding of nuclear facilities, GKTC has begun to develop the specialized training courses for the guarding unit personnel. The evaluation of needs of training of Ukrainian specialists on the physical protection shows that without the technical base of learning is not possible to satisfy the needs of Ukrainian facilities, in particular, the need for further training of specialists who maintains physical protection technical means, provides vulnerability assessment and testing of technical means. To increase the training effectiveness and create the basis for specialized training courses holding the GKTC is now working on the construction of an Interior (non-classified) Physical Protection Training Site. The objective of this site is to simulate the actual conditions of the nuclear facility PP system including the complex of engineering and technical means that will help the GKTC training course participants to consolidate the knowledge and gain the practical skills in the work with PP system engineering and technical means for more effective performance of their official duties. This paper

Recruitment of activated IRF-3 and CBP/p300 to herpes simplex virus ICP0 nuclear foci: Potential role in blocking IFN-{beta} induction

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

Melroe, Gregory T.; Silva, Lindsey; Schaffer, Priscilla A.

2007-04-10

The host innate response to viral infection includes the production of interferons, which is dependent on the coordinated activity of multiple transcription factors. Herpes simplex virus 1 (HSV-1) has been shown to block efficient interferon expression by multiple mechanisms. We and others have demonstrated that HSV-1 can inhibit the transcription of genes promoted by interferon regulatory factor-3 (IRF-3), including interferon beta (IFN-{beta}), and that the immediate-early ICP0 protein is sufficient for this function. However, the exact mechanism by which ICP0 blocks IRF-3 activity has yet to be determined. Unlike some other viral proteins that inhibit IRF-3 activity, ICP0 does notmore » appear to affect phosphorylation and dimerization of IRF-3. Here, we show that a portion of activated IRF-3 co-localizes with nuclear foci containing ICP0 at early times after virus infection. Co-localization to ICP0-containing foci is also seen with the IRF-3-binding partners and transcriptional co-activators, CBP and p300. In addition, using immunoprecipitation of infected cell lysates, we can immunoprecipitate a complex containing ICP0, IRF-3, and CBP. Thus we hypothesize that ICP0 recruits activated IRF-3 and CBP/p300 to nuclear structures, away from the host chromatin. This leads to the inactivation and accelerated degradation of IRF-3, resulting in reduced transcription of IFN-{beta} and an inhibition of the host response. Therefore, ICP0 provides an example of how viruses can block IFN-{beta} induction by sequestration of important transcription factors essential for the host response.« less

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 systems for space power and propulsion

NASA Technical Reports Server (NTRS)

Klein, M.

1971-01-01

As exploration and utilization of space proceeds through the 1970s, 1980s, and beyond, spacecraft in earth orbit will become increasingly larger, spacecraft will travel deeper into space, and space activities will involve more complex operations. These trends require increasing amounts of energy for power and propulsion. The role to be played by nuclear energy is presented, including plans for deep space missions using radioisotope generators, the reactor power systems for earth orbiting stations and satellites, and the role of nuclear propulsion in space transportation.

Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells.

PubMed

Pettazzoni, Piergiorgio; Ciamporcero, Eric; Medana, Claudio; Pizzimenti, Stefania; Dal Bello, Federica; Minero, Valerio Giacomo; Toaldo, Cristina; Minelli, Rosalba; Uchida, Koji; Dianzani, Mario Umberto; Pili, Roberto; Barrera, Giuseppina

2011-10-15

4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparative Evaluation of Cutting Methods of Activated Concrete from Nuclear Power Plant Decommissioning - 13548

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

Kim, HakSoo; Chung, SungHwan; Maeng, SungJun

2013-07-01

The amount of radioactive wastes from decommissioning of a nuclear power plant varies greatly depending on factors such as type and size of the plant, operation history, decommissioning options, and waste treatment and volume reduction methods. There are many methods to decrease the amount of decommissioning radioactive wastes including minimization of waste generation, waste reclassification through decontamination and cutting methods to remove the contaminated areas. According to OECD/NEA, it is known that the radioactive waste treatment and disposal cost accounts for about 40 percentage of the total decommissioning cost. In Korea, it is needed to reduce amount of decommissioning radioactivemore » waste due to high disposal cost, about $7,000 (as of 2010) per a 200 liter drum for the low- and intermediate-level radioactive waste (LILW). In this paper, cutting methods to minimize the radioactive waste of activated concrete were investigated and associated decommissioning cost impact was assessed. The cutting methods considered are cylindrical and volume reductive cuttings. The study showed that the volume reductive cutting is more cost-effective than the cylindrical cutting. Therefore, the volume reductive cutting method can be effectively applied to the activated bio-shield concrete. (authors)« less

Hydroquinone stimulates inflammatory functions in microvascular endothelial cells via NF-κB nuclear activation.

PubMed

Hebeda, Cristina Bichels; Pinedo, Fernanda Júdice; Vinolo, Marco Aurélio Ramirez; Curi, Rui; Farsky, Sandra Helena Poliselli

2011-11-01

Hydroquinone impairs several leucocyte cell functions, which alter the immune response. Although endothelial cell functions are important for the development of immune responses, hydroquinone actions on endothelial cell have not been shown. Therefore, the effect of hydroquinone exposure (10 or 100 μM for 2 hr) on primary culture of microvascular endothelial cells (PMECs) obtained from the cremaster muscle of Wistar rats incubated in the presence or absence of lipopolysaccharide (LPS, 2 μg/mL) was investigated. Hydroquinone treatment induced the membrane expression of cell adhesion molecules (CAMs) from the immunoglobulin superfamilies ICAM-1 (intercellular), VCAM-1(vascular) and PECAM-1 (platelet endothelial) and induced the secretion of cytokines interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α). The effects were dependent on transcriptional modifications because enhanced CAM mRNA expression as well as both cytokines and nuclear factor κB (NF-κB) nuclear activation was found. These effects may be due to the direct action of hydroquinone rather than its quinone metabolites, because endothelial cells do not present myeloperoxidase enzyme and hydroquinone incubation did not induce the expression of cytochrome P450 2E1 (CYP2E1) or prostaglandin H synthase 1. In addition, the incubation of endothelial cells with benzoquinone (10 μM, 2 hr) impaired PECAM-1 expression and did not modify NF-κB nuclear activation. Taken together, the data herein presented reveal that hydroquinone evokes pro-inflammatory properties in endothelial cells that are triggered by the enhancement of NF-κB nuclear translocation-dependent gene transcription. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

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

Evidence for activation of nuclear factor kappaB in obstructive sleep apnea.

PubMed

Yamauchi, Motoo; Tamaki, Shinji; Tomoda, Koichi; Yoshikawa, Masanori; Fukuoka, Atsuhiko; Makinodan, Kiyoshi; Koyama, Noriko; Suzuki, Takahiro; Kimura, Hiroshi

2006-12-01

Obstructive sleep apnea (OSA) is a risk factor for atherosclerosis, and atherosclerosis evolves from activation of the inflammatory cascade. We propose that activation of the nuclear factor kappaB (NF-kappaB), a key transcription factor in the inflammatory cascade, occurs in OSA. Nine age-matched, nonsmoking, and non-hypertensive men with OSA symptoms and seven similar healthy subjects were recruited for standard polysomnography followed by the collection of blood samples for monocyte nuclear p65 concentrations (OSA and healthy groups). In the OSA group, p65 and of monocyte production of tumor necrosis factor alpha (TNF-alpha) were measured at the same time and after the next night of continuous positive airway pressure (CPAP). p65 Concentrations in the OSA group were significantly higher than in the control group [median, 0.037 ng/microl (interquartile range, 0.034 to 0.051) vs 0.019 ng/microl (interquartile range, 0.013 to 0.032); p = 0.008], and in the OSA group were significantly correlated with apnea-hypopnea index and time spent below an oxygen saturation of 90% (r = 0.77 and 0.88, respectively) after adjustment for age and BMI. One night of CPAP resulted in a reduction in p65 [to 0.020 ng/mul (interquartile range, 0.010 to 0.036), p = 0.04] and levels of TNF-alpha production in cultured monocytes [16.26 (interquartile range, 7.75 to 24.85) to 7.59 ng/ml (interquartile range, 5.19 to 12.95), p = 0.01]. NF-kappaB activation occurs with sleep-disordered breathing. Such activation of NF-kappaB may contribute to the pathogenesis of atherosclerosis in OSA patients.

Actinide targets for fundamental research in nuclear physics

NASA Astrophysics Data System (ADS)

Eberhardt, K.; Düllmann, Ch. E.; Haas, R.; Mokry, Ch.; Runke, J.; Thörle-Pospiech, P.; Trautmann, N.

2018-05-01

Thin actinide layers deposited on various substrates are widely used as calibration sources in nuclear spectroscopy. Other applications include fundamental research in nuclear chemistry and -physics, e.g., the chemical and physical properties of super-heavy elements (SHE, Z > 103) or nuclear reaction studies with heavy ions. For the design of future nuclear reactors like fast-fission reactors and accelerator-driven systems for transmutation of nuclear waste, precise data for neutron absorption as well as neutron-induced fission cross section data for 242Pu with neutrons of different energies are of particular importance, requiring suitable Pu-targets. Another application includes studies of nuclear transitions in 229Th harvested as α-decay recoil product from a thin layer of its 233U precursor. For this, a thin and very smooth layer of 233U is used. We report here on the production of actinide layers mostly obtained by Molecular Plating (MP). MP is currently the only fabrication method in cases where the desired actinide material is available only in very limited amounts or possesses a high specific activity. Here, deposition is performed from organic solution applying a current density of 1-2 mA/cm2. Under these conditions target thicknesses of 500-1000 μg/cm2 are possible applying a single deposition step with deposition yields approaching 100 %. For yield determination α-particle spectroscopy, γ-spectroscopy and Neutron Activation Analysis is routinely used. Layer homogeneity is checked with Radiographic Imaging. As an alternative technique to MP the production of thin lanthanide and actinide layers by the so-called "Drop on Demand"-technique applied e.g., in ink-jet printing is currently under investigation.

5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation.

PubMed

Gerstmeier, Jana; Newcomer, Marcia E; Dennhardt, Sophie; Romp, Erik; Fischer, Jana; Werz, Oliver; Garscha, Ulrike

2016-05-01

Leukotrienes (LTs) are proinflammatory lipid mediators formed from arachidonic acid in a 2-step reaction catalyzed by 5-lipoxygenase (5-LOX) requiring the formation of 5-HPETE [5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid] and its subsequent transformation to LTA4 5-LOX is thought to receive arachidonic acid from the nuclear membrane-embedded 5-LOX-activating protein (FLAP). The crystal structure of 5-LOX revealed an active site concealed by F177 and Y181 (FY cork). We examined the influence of the FY cork on 5-LOX activity and membrane binding in HEK293 cells in the absence and presence of FLAP. Uncapping the 5-LOX active site by mutation of F177 and/or Y181 to alanine (5-LOX-F177A, 5-LOX-Y181A, 5-LOX-F177/Y181A) resulted in delayed and diminished 5-LOX membrane association in A23187-stimulated cells. For 5-LOX-F177A and 5-LOX-F177/Y181A, formation of 5-LOX products was dramatically reduced relative to 5-LOX-wild type (wt). Strikingly, coexpression of FLAP in A23187-activated HEK293 cells effectively restored formation of 5-H(p)ETE (5-hydroxy- and 5-peroxy-6-trans-8,11,14-cis-eicosatetraenoic acid) by these same 5-LOX mutants (≈60-70% 5-LOX-wt levels) but not of LTA4 hydrolysis products. Yet 5-LOX-Y181A generated 5-H(p)ETE at levels comparable to 5-LOX-wt but reduced LTA4 hydrolysis products. Coexpression of FLAP partially restored LTA4 hydrolysis product formation by 5-LOX-Y181A. Together, the data suggest that the concealed FY cork impacts membrane association and that FLAP may help shield an uncapped active site.-Gerstmeier, J., Newcomer, M. E., Dennhardt, S., Romp, E., Fischer, J., Werz, O., Garscha, U. 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation. © FASEB.

KLF4 Nuclear Export Requires ERK Activation and Initiates Exit from Naive Pluripotency.

PubMed

Dhaliwal, Navroop K; Miri, Kamelia; Davidson, Scott; Tamim El Jarkass, Hala; Mitchell, Jennifer A

2018-04-10

Cooperative action of a transcription factor complex containing OCT4, SOX2, NANOG, and KLF4 maintains the naive pluripotent state; however, less is known about the mechanisms that disrupt this complex, initiating exit from pluripotency. We show that, as embryonic stem cells (ESCs) exit pluripotency, KLF4 protein is exported from the nucleus causing rapid decline in Nanog and Klf4 transcription; as a result, KLF4 is the first pluripotency transcription factor removed from transcription-associated complexes during differentiation. KLF4 nuclear export requires ERK activation, and phosphorylation of KLF4 by ERK initiates interaction of KLF4 with nuclear export factor XPO1, leading to KLF4 export. Mutation of the ERK phosphorylation site in KLF4 (S132) blocks KLF4 nuclear export, the decline in Nanog, Klf4, and Sox2 mRNA, and differentiation. These findings demonstrate that relocalization of KLF4 to the cytoplasm is a critical first step in exit from the naive pluripotent state and initiation of ESC differentiation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Tungsten - Yttrium Based Nuclear Structural Materials

NASA Astrophysics Data System (ADS)

Ramana, Chintalapalle; Chessa, Jack; Martinenz, Gustavo

2013-04-01

The challenging problem currently facing the nuclear science community in this 21st century is design and development of novel structural materials, which will have an impact on the next-generation nuclear reactors. The materials available at present include reduced activation ferritic/martensitic steels, dispersion strengthened reduced activation ferritic steels, and vanadium- or tungsten-based alloys. These materials exhibit one or more specific problems, which are either intrinsic or caused by reactors. This work is focussed towards tungsten-yttrium (W-Y) based alloys and oxide ceramics, which can be utilized in nuclear applications. The goal is to derive a fundamental scientific understanding of W-Y-based materials. In collaboration with University of Califonia -- Davis, the project is designated to demonstrate the W-Y based alloys, ceramics and composites with enhanced physical, mechanical, thermo-chemical properties and higher radiation resistance. Efforts are focussed on understanding the microstructure, manipulating materials behavior under charged-particle and neutron irradiation, and create a knowledge database of defects, elemental diffusion/segregation, and defect trapping along grain boundaries and interfaces. Preliminary results will be discussed.

Microsomal receptor for steroid hormones: functional implications for nuclear activity.

PubMed

Muldoon, T G; Watson, G H; Evans, A C; Steinsapir, J

1988-01-01

Target tissues for steroid hormones are responsive by virtue of and to the extent of their content of functional intracellular receptors. Recent years have seen a shift in considerations of the cellular dynamics and distribution of these receptors, with current views favoring predominant intranuclear localization in the intact cell. This paper summarizes our analyses of the microsomal estrogen and androgen binding capability of rat uterine and ventral prostate tissue, respectively; these studies have revealed a set of high affinity sites that may act as a conduit for estrogen traversing the cell en route to the nucleus. These sites have many properties in common with cytosolic receptors, with the salient difference of a failure to activate to a more avid DNA-binding form under conditions which permit such activation of cytosolic receptors. The microsomal estrogen-binding proteins also have appreciable affinity for progesterone, another distinction from other known cellular estrogen receptor species. Various experimental approaches were employed to demonstrate that the microsomal receptors were not simply cytosol contaminants; the most convincing evidence is the recent successful separation of the cytosolic and microsomal forms by differential ammonium sulfate precipitation. Discrete subfractionation of subcellular components on successive sucrose gradients, with simultaneous assessments of binding capability and marker enzyme concentrations, indicates that the major portion of the binding is localized within the vesicles of the endoplasmic reticulum free of significant plasma membrane contamination. The microsomal receptors are readily solubilized by extraction with high- or low-salt-containing buffers or with steroid. The residual microsomes following such extraction have the characteristics of saturable acceptor sites for cytosolic estrogen-receptor complexes. The extent to which these sites will accept the cytosolic complexes is equal to the concentration of

Nuclear choices

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

Wolfson, R.

This book contains part of the series New Liberal Arts, which is intended to make science and technology more accessible to students of the liberal arts. Volume in hand provides a comprehensive, multifaceted examination of nuclear energy, in nontechnical terms. Wolfson explains the basics of nuclear energy and radiation, nuclear power..., and nuclear weapons..., and he invites readers to make their own judgments on controversial nuclear issues. Illustrated with photos and diagrams. Each chapter contains suggestions for additional reading and a glossary. For policy, science, and general collections in all libraries. (ES) Topics contained include Atoms and nuclei. Effects andmore » uses of radiation. Energy and People. Reactor safety. Nuclear strategy. Defense in the nuclear age. Nuclear power, nuclear weapons, and nuclear futures.« less

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

Nesprin-1α-Dependent Microtubule Nucleation from the Nuclear Envelope via Akap450 Is Necessary for Nuclear Positioning in Muscle Cells.

PubMed

Gimpel, Petra; Lee, Yin Loon; Sobota, Radoslaw M; Calvi, Alessandra; Koullourou, Victoria; Patel, Rutti; Mamchaoui, Kamel; Nédélec, François; Shackleton, Sue; Schmoranzer, Jan; Burke, Brian; Cadot, Bruno; Gomes, Edgar R

2017-10-09

The nucleus is the main microtubule-organizing center (MTOC) in muscle cells due to the accumulation of centrosomal proteins and microtubule (MT) nucleation activity at the nuclear envelope (NE) [1-4]. The relocalization of centrosomal proteins, including Pericentrin, Pcm1, and γ-tubulin, depends on Nesprin-1, an outer nuclear membrane (ONM) protein that connects the nucleus to the cytoskeleton via its N-terminal region [5-7]. Nesprins are also involved in the recruitment of kinesin to the NE and play a role in nuclear positioning in skeletal muscle cells [8-12]. However, a function for MT nucleation from the NE in nuclear positioning has not been established. Using the proximity-dependent biotin identification (BioID) method [13, 14], we found several centrosomal proteins, including Akap450, Pcm1, and Pericentrin, whose association with Nesprin-1α is increased in differentiated myotubes. We show that Nesprin-1α recruits Akap450 to the NE independently of kinesin and that Akap450, but not other centrosomal proteins, is required for MT nucleation from the NE. Furthermore, we demonstrate that this mechanism is disrupted in congenital muscular dystrophy patient myotubes carrying a nonsense mutation within the SYNE1 gene (23560 G>T) encoding Nesprin-1 [15, 16]. Finally, using computer simulation and cell culture systems, we provide evidence for a role of MT nucleation from the NE on nuclear spreading in myotubes. Our data thus reveal a novel function for Nesprin-1α/Nesprin-1 in nuclear positioning through recruitment of Akap450-mediated MT nucleation activity to the NE. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The AEC-NASA Nuclear Rocket Program

NASA Astrophysics Data System (ADS)

Finger, Harold B.

2002-01-01

The early days and years of the National Aeronautics and Space Administration (NASA), its assigned missions its organization and program development, provided major opportunities for still young technical people to participate in and contribute to making major technological advances and to broaden and grow their technical, management, and leadership capabilities for their and our country's and the world's benefit. Being one of those fortunate beneficiaries while I worked at NASA's predecessor, the National Advisory Committee for Aeronautics (NACA) Lewis Flight Propulsion Laboratory in Cleveland and then when I was transferred to the NASA Headquarters on October 1, 1958, the day NASA was formally activated, this paper will describe some of my experiences and their significant results, including the personal benefits I derived from that fabulous period of our major national accomplishments. Although I had a broad range of responsibility in NASA which changed and grew over time, I concentrate my discussion in this paper on those activities conducted by NASA and the Atomic Energy Committee (AEC) in the development of the technology of nuclear rocket propulsion to enable the performance of deep space missions. There are two very related but distinct elements of this memoir. One relates to NASA's and the U.S. missions in those very early years and some of the technical and administrative elements as well as the political influences and interagency activities, including primarily the AEC and NASA, as well as diverse industrial and governmental capabilities and activities required to permit the new NASA to accomplish its assigned mission responsibilities. The other concerns the more specific technical and management assignments used to achieve the program's major technological successes. I will discuss first, how and why I was assigned to manage those nuclear rocket propulsion program activities and, then, how we achieved our very significant and successful program

Suppression of lipopolysaccharide-induced nuclear factor-kappaB activity by theaflavin-3,3'-digallate from black tea and other polyphenols through down-regulation of IkappaB kinase activity in macrophages.

PubMed

Pan, M H; Lin-Shiau, S Y; Ho, C T; Lin, J H; Lin, J K

2000-02-15

We investigated the inhibition of IkappaB kinase (IKK) activity in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 cell line) by various polyphenols including (-)-epigallocatechin-3-gallate, theaflavin, a mixture of theaflavin-3 gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), pyrocyanidin B-3, casuarinin, geraniin, and penta-O-galloyl-beta-D-glucose (5GG). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other polyphenols. TF-3 strongly inhibited both IKK1 and IKK2 activity and prevented the degradation of IkappaBalpha and IkappaBbeta in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. Furthermore, geraniin, 5GG, and TF-3 all blocked phosphorylation of IKB from the cytosolic fraction, inhibited nuclear factor-kappaB (NFkappaB) activity, and inhibited increases in inducible nitric oxide synthase levels in activated macrophages. These results suggest that TF-3 may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IKK activity.

Moving Cell Boundaries Drive Nuclear Shaping during Cell Spreading

PubMed Central

Li, Yuan; Lovett, David; Zhang, Qiao; Neelam, Srujana; Kuchibhotla, Ram Anirudh; Zhu, Ruijun; Gundersen, Gregg G.; Lele, Tanmay P.; Dickinson, Richard B.

2015-01-01

The nucleus has a smooth, regular appearance in normal cells, and its shape is greatly altered in human pathologies. Yet, how the cell establishes nuclear shape is not well understood. We imaged the dynamics of nuclear shaping in NIH3T3 fibroblasts. Nuclei translated toward the substratum and began flattening during the early stages of cell spreading. Initially, nuclear height and width correlated with the degree of cell spreading, but over time, reached steady-state values even as the cell continued to spread. Actomyosin activity, actomyosin bundles, microtubules, and intermediate filaments, as well as the LINC complex, were all dispensable for nuclear flattening as long as the cell could spread. Inhibition of actin polymerization as well as myosin light chain kinase with the drug ML7 limited both the initial spreading of cells and flattening of nuclei, and for well-spread cells, inhibition of myosin-II ATPase with the drug blebbistatin decreased cell spreading with associated nuclear rounding. Together, these results show that cell spreading is necessary and sufficient to drive nuclear flattening under a wide range of conditions, including in the presence or absence of myosin activity. To explain this observation, we propose a computational model for nuclear and cell mechanics that shows how frictional transmission of stress from the moving cell boundaries to the nuclear surface shapes the nucleus during early cell spreading. Our results point to a surprisingly simple mechanical system in cells for establishing nuclear shapes. PMID:26287620

Nuclear Radio Jet from a Low-luminosity Active Galactic Nucleus in NGC 4258

NASA Astrophysics Data System (ADS)

Doi, Akihiro; Kohno, Kotaro; Nakanishi, Kouichiro; Kameno, Seiji; Inoue, Makoto; Hada, Kazuhiro; Sorai, Kazuo

2013-03-01

The nearby low-luminosity active galactic nucleus (LLAGN) NGC 4258 has a weak radio continuum component at the galactic center. We investigate its radio spectral properties on the basis of our new observations using the Nobeyama Millimeter Array at 100 GHz and archival data from the Very Large Array at 1.7-43 GHz and the James Clerk Maxwell telescope at 347 GHz. The NGC 4258 nuclear component exhibits (1) an intra-month variable and complicated spectral feature at 5-22 GHz and (2) a slightly inverted spectrum at 5-100 GHz (α ~ 0.3; F νvpropνα) in time-averaged flux densities, which are also apparent in the closest LLAGN M81. These similarities between NGC 4258 and M81 in radio spectral natures in addition to previously known core shift in their AU-scale jet structures produce evidence that the same mechanism drives their nuclei. We interpret the observed spectral property as the superposition of emission spectra originating at different locations with frequency-dependent opacity along the nuclear jet. Quantitative differences between NGC 4258 and M81 in terms of jet/counter jet ratio, radio loudness, and degree of core shift can be consistently understood by fairly relativistic speeds (Γ >~ 3) of jets and their quite different inclinations. The picture established from the two closest LLAGNs is useful for understanding the physical origin of unresolved and flat/inverted spectrum radio cores that are prevalently found in LLAGNs, including Sgr A*, with starved supermassive black holes in the present-day universe.

Nuclear pore complex evolution: a trypanosome Mlp analogue functions in chromosomal segregation but lacks transcriptional barrier activity

PubMed Central

Holden, Jennifer M.; Koreny, Ludek; Obado, Samson; Ratushny, Alexander V.; Chen, Wei-Ming; Chiang, Jung-Hsien; Kelly, Steven; Chait, Brian T.; Aitchison, John D.; Rout, Michael P.; Field, Mark C.

2014-01-01

The nuclear pore complex (NPC) has dual roles in nucleocytoplasmic transport and chromatin organization. In many eukaryotes the coiled-coil Mlp/Tpr proteins of the NPC nuclear basket have specific functions in interactions with chromatin and defining specialized regions of active transcription, whereas Mlp2 associates with the mitotic spindle/NPC in a cell cycle–dependent manner. We previously identified two putative Mlp-related proteins in African trypanosomes, TbNup110 and TbNup92, the latter of which associates with the spindle. We now provide evidence for independent ancestry for TbNup92/TbNup110 and Mlp/Tpr proteins. However, TbNup92 is required for correct chromosome segregation, with knockout cells exhibiting microaneuploidy and lowered fidelity of telomere segregation. Further, TbNup92 is intimately associated with the mitotic spindle and spindle anchor site but apparently has minimal roles in control of gene transcription, indicating that TbNup92 lacks major barrier activity. TbNup92 therefore acts as a functional analogue of Mlp/Tpr proteins, and, together with the lamina analogue NUP-1, represents a cohort of novel proteins operating at the nuclear periphery of trypanosomes, uncovering complex evolutionary trajectories for the NPC and nuclear lamina. PMID:24600046

Needs for Robotic Assessments of Nuclear Disasters

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

Victor Walker; Derek Wadsworth

Following the nuclear disaster at the Fukushima nuclear reactor plant in Japan, the need for systems which can assist in dynamic high-radiation environments such as nuclear incidents has become more apparent. The INL participated in delivering robotic technologies to Japan and has identified key components which are needed for success and obstacles to their deployment. In addition, we are proposing new work and methods to improve assessments and reactions to such events in the future. Robotics needs in disaster situations include phases such as: Assessment, Remediation, and Recovery Our particular interest is in the initial assessment activities. In assessment wemore » need collection of environmental parameters, determination of conditions, and physical sample collection. Each phase would require key tools and efforts to develop. This includes study of necessary sensors and their deployment methods, the effects of radiation on sensors and deployment, and the development of training and execution systems.« less

Nuclear War and Science Teaching.

ERIC Educational Resources Information Center

Hobson, Art

1983-01-01

Suggests that science-related material on nuclear war be included in introductory courses. Lists nuclear war topics for physics, psychology, sociology, biology/ecology, chemistry, geography, geology/meteorology, mathematics, and medical science. Also lists 11 lectures on nuclear physics which include nuclear war topics. (JN)

Midwest Nuclear Science and Engineering Consortium

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

Dr. Wynn Volkert; Dr. Arvind Kumar; Dr. Bryan Becker

2010-12-08

The objective of the Midwest Nuclear Science and Engineering Consortium (MNSEC) is to enhance the scope, quality and integration of educational and research capabilities of nuclear sciences and engineering (NS/E) programs at partner schools in support of the U.S. nuclear industry (including DOE laboratories). With INIE support, MNSEC had a productive seven years and made impressive progress in achieving these goals. Since the past three years have been no-cost-extension periods, limited -- but notable -- progress has been made in FY10. Existing programs continue to be strengthened and broadened at Consortium partner institutions. The enthusiasm generated by the academic, state,more » federal, and industrial communities for the MNSEC activities is reflected in the significant leveraging that has occurred for our programs.« less

Nuclear structure and decay data evaluation in Europe

NASA Astrophysics Data System (ADS)

Negret, Alexandru; Balabanski, Dimiter; Dimitriou, Paraskevi; Elekes, Zoltan; Mertzimekis, Theo J.; Pascu, Sorin; Timar, Janos

2017-09-01

Nuclear Structure and Decay Data (NSDD) activities in Europe include mass-chain and individual nuclei evaluations as well as horizontal evaluations and compilations, data dissemination and educational activities. As such they are essential for a large range of applications from energy, environmental, and medical to basic research in nuclear structure and reactions, all of which are intensively pursued in Europe. Although the NSDD evaluation groups in Europe form part of the international network of NSDD evaluators, which is coordinated by the International Atomic Energy Agency, they are faced with some very distinct challenges. We shortly present the NSDD Data Centre at IFIN-HH, Bucharest and discuss possible actions to improve the situation for the entire European NSDD evaluation effort.

Guide for Operational Configuration Management Program including the adjunct programs of design reconstitution and material condition and aging management. Part 1

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

Not Available

This standard presents program criteria and implementation guidance for an operational configuration management program for DOE nuclear and non-nuclear facilities in the operational phase. Portions of this standard are also useful for other DOE processes, activities, and programs. This Part 1 contains foreword, glossary, acronyms, bibliography, and Chapter 1 on operational configuration management program principles. Appendices are included on configuration management program interfaces, and background material and concepts for operational configuration management.

Exploring the Use of Activity Patterns for Smart Monitoring of Nuclear Facilities

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

Miller, Karen Ann

The world is at an inflection point where our ability to collect data now far outpaces our ability to make use of it. LANL has a number of efforts to help us pull more meaningful insights out of our data and target resources to where they will be most impactful. We are exploring an approach to recognizing activity patterns across disparate data streams for a more holistic view of nuclear facility monitoring.

Subcellular localization of calcium and Ca-ATPase activity during nuclear maturation in Bufo arenarum oocytes.

PubMed

Ramos, Inés; Cisint, Susana B; Crespo, Claudia A; Medina, Marcela F; Fernández, Silvia N

2009-08-01

The localization of calcium and Ca-ATPase activity in Bufo arenarum oocytes was investigated by ultracytochemical techniques during progesterone-induced nuclear maturation, under in vitro conditions. No Ca2+ deposits were detected in either control oocytes or progesterone-treated ones for 1-2 h. At the time when nuclear migration started, electron dense deposits of Ca2+ were visible in vesicles, endoplasmic reticulum cisternae and in the space between the annulate lamellae membranes. Furthermore, Ca-ATPase activity was also detected in these membrane structures. As maturation progressed, the cation deposits were observed in the cytomembrane structures, which underwent an important reorganization and redistribution. Thus, they moved from the subcortex and became located predominantly in the oocyte cortex area when nuclear maturation ended. Ca2+ stores were observed in vesicles surrounding or between the cortical granules, which are aligned close to the plasma membrane. The positive Ca-ATPase reaction in these membrane structures could indicate that the calcium deposit is an ATP-dependent process. Our results suggest that during oocyte maturation calcium would be stored in membrane structures where it remains available for release at the time of fertilization. Data obtained under our experimental conditions indicate that calcium from the extracellular medium would be important for the oocyte maturation process.

cAMP-dependent protein kinase phosphorylates and activates nuclear Ca2+-ATPase

PubMed Central

Rogue, Patrick J.; Humbert, Jean-Paul; Meyer, Alphonse; Freyermuth, Solange; Krady, Marie-Marthe; Malviya, Anant N.

1998-01-01

A Ca2+-pump ATPase, similar to that in the endoplasmic reticulum, has been located on the outer membrane of rat liver nuclei. The effect of cAMP-dependent protein kinase (PKA) on nuclear Ca2+-ATPase (NCA) was studied by using purified rat liver nuclei. Treatment of isolated nuclei with the catalytic unit of PKA resulted in the phosphorylation of a 105-kDa band that was recognized by antibodies specific for sarcoplasmic reticulum Ca2+-ATPase type 2b. Partial purification and immunoblotting confirmed that the 105-kDa protein band phosphorylated by PKA is NCA. The stoichiometry of phosphorylation was 0.76 mol of phosphate incorporated/mol of partially purified enzyme. Measurement of ATP-dependent 45Ca2+ uptake into purified nuclei showed that PKA phosphorylation enhanced the Ca2+-pumping activity of NCA. We show that PKA phosphorylation of Ca2+-ATPase enhances the transport of 10-kDa fluorescent-labeled dextrans across the nuclear envelope. The findings reported in this paper are consistent with the notion that the crosstalk between the cAMP/PKA- and Ca2+-dependent signaling pathways identified at the cytoplasmic level extends to the nucleus. Furthermore, these data support a function for crosstalk in the regulation of calcium-dependent transport across the nuclear envelope. PMID:9689054

Effects of Nuclear Weapons.

ERIC Educational Resources Information Center

Sartori, Leo

1983-01-01

Fundamental principles governing nuclear explosions and their effects are discussed, including three components of a nuclear explosion (thermal radiation, shock wave, nuclear radiation). Describes how effects of these components depend on the weapon's yield, its height of burst, and distance of detonation point. Includes effects of three…

Nuclear Thermal Rocket Element Environmental Simulator (NTREES) Upgrade Activities

NASA Technical Reports Server (NTRS)

Emrich, William J. Jr.; Moran, Robert P.; Pearson, J. Boise

2012-01-01

To support the on-going nuclear thermal propulsion effort, a state-of-the-art non nuclear experimental test setup has been constructed to evaluate the performance characteristics of candidate fuel element materials and geometries in representative environments. The facility to perform this testing is referred to as the Nuclear Thermal Rocket Element Environment Simulator (NTREES). This device can simulate the environmental conditions (minus the radiation) to which nuclear rocket fuel components will be subjected during reactor operation. Test articles mounted in the simulator are inductively heated in such a manner so as to accurately reproduce the temperatures and heat fluxes which would normally occur as a result of nuclear fission and would be exposed to flowing hydrogen. Initial testing of a somewhat prototypical fuel element has been successfully performed in NTREES and the facility has now been shutdown to allow for an extensive reconfiguration of the facility which will result in a significant upgrade in its capabilities

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...

Development of automation software for neutron activation analysis process in Malaysian nuclear agency

NASA Astrophysics Data System (ADS)

Yussup, N.; Rahman, N. A. A.; Ibrahim, M. M.; Mokhtar, M.; Salim, N. A. A.; Soh@Shaari, S. C.; Azman, A.

2017-01-01

Neutron Activation Analysis (NAA) process has been established in Malaysian Nuclear Agency (Nuclear Malaysia) since 1980s. Most of the procedures established especially from sample registration to sample analysis are performed manually. These manual procedures carried out by the NAA laboratory personnel are time consuming and inefficient. Hence, a software to support the system automation is developed to provide an effective method to replace redundant manual data entries and produce faster sample analysis and calculation process. This paper describes the design and development of automation software for NAA process which consists of three sub-programs. The sub-programs are sample registration, hardware control and data acquisition; and sample analysis. The data flow and connection between the sub-programs will be explained. The software is developed by using National Instrument LabView development package.

Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.

PubMed

Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter

2013-07-01

Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.

PubMed

Van Huffel, S; Delaei, F; Heyninck, K; De Valck, D; Beyaert, R

2001-08-10

The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.

CIRFT Data Update and Data Analyses for Spent Nuclear Fuel Vibration Reliability Study

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

Wang, Jy-An John; Wang, Hong

The objective of this research is to collect experimental data on spent nuclear fuel (SNF) from pressurized water reactors (PWRs), including the H. B. Robinson Nuclear Power Station (HBR), Catawba Nuclear Station, North Anna Nuclear Power Station (NA), and the Limerick Nuclear Power Station (LMK) boiling water reactor (BWR). Data will be collected under simulated transportation environments using the cyclic integrated reversible-bending fatigue tester (CIRFT), an enabling hot-cell testing technology developed at Oak Ridge National Laboratory (ORNL). These data will be used to support ongoing SNF modeling activities and to address regulatory issues associated with SNF transport.

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

Macrophage activation by polysaccharides from Atractylodes macrocephala Koidz through the nuclear factor-κB pathway.

PubMed

Ji, Guang-Quan; Chen, Ren-Qiong; Zheng, Jian-Xian

2015-04-01

Atractylodes macrocephala Koidz is a traditional herb. Atractylodes macrocephalaon polysaccharides (AMP) have been found to enhance immunity and improve heart function. However, the mechanisms of the immunomodulatory effect have not been investigated. We examined whether AMP activated macrophages and explored the mechanisms of activation. AMP was prepared and evaluated its immunomodulatory activity (25, 50, 100, and 200 μg/mL) by detecting the phagocytosis and the production of tumor necrosis factor-α (TNF-α), IFN-γ, and nitric oxide (NO) in RAW264.7 macrophages. Furthermore, the role of nuclear factor-κB (NF-κB) pathway was examined in regulating TNF-α and NO production. The phagocytosis of macrophages was enhanced by AMP in a dose-dependent manner and the maximal phagocytosis of macrophages occurred at concentrations of 100 and 200 μg/mL. NO, TNF-α, and IFN-γ release was also found to be dose dependent by increasing concentrations of AMP and reached the peak at a concentration of 200 μg/mL. In addition, AMP induced inhibitor kappaB (IκB) degradation and the activation of NF-κB by p65 nuclear translocation, and then the activation of NF-κB in nucleus peaked at a concentration of 200 μg/mL. Besides, NF-κB-specific inhibitor pyrrolidine dithiocarbamate (PDTC) decreased AMP-induced NO and TNF-α production. These data suggest that AMP may modulate macrophage activities by stimulating NF-κB or activating NF-κB-dependent mechanisms.

Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

PubMed

Pinsky, C; Dua, A K; LaBella, F S

1982-07-15

Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

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.

From the first nuclear power plant to fourth-generation nuclear power installations [on the 60th anniversary of the World's First nuclear power plant

NASA Astrophysics Data System (ADS)

Rachkov, V. I.; Kalyakin, S. G.; Kukharchuk, O. F.; Orlov, Yu. I.; Sorokin, A. P.

2014-05-01

Successful commissioning in the 1954 of the World's First nuclear power plant constructed at the Institute for Physics and Power Engineering (IPPE) in Obninsk signaled a turn from military programs to peaceful utilization of atomic energy. Up to the decommissioning of this plant, the AM reactor served as one of the main reactor bases on which neutron-physical investigations and investigations in solid state physics were carried out, fuel rods and electricity generating channels were tested, and isotope products were bred. The plant served as a center for training Soviet and foreign specialists on nuclear power plants, the personnel of the Lenin nuclear-powered icebreaker, and others. The IPPE development history is linked with the names of I.V. Kurchatov, A.I. Leipunskii, D.I. Blokhintsev, A.P. Aleksandrov, and E.P. Slavskii. More than 120 projects of various nuclear power installations were developed under the scientific leadership of the IPPE for submarine, terrestrial, and space applications, including two water-cooled power units at the Beloyarsk NPP in Ural, the Bilibino nuclear cogeneration station in Chukotka, crawler-mounted transportable TES-3 power station, the BN-350 reactor in Kazakhstan, and the BN-600 power unit at the Beloyarsk NPP. Owing to efforts taken on implementing the program for developing fast-neutron reactors, Russia occupied leading positions around the world in this field. All this time, IPPE specialists worked on elaborating the principles of energy supertechnologies of the 21st century. New large experimental installations have been put in operation, including the nuclear-laser setup B, the EGP-15 accelerator, the large physical setup BFS, the high-pressure setup SVD-2; scientific, engineering, and technological schools have been established in the field of high- and intermediate-energy nuclear physics, electrostatic accelerators of multicharge ions, plasma processes in thermionic converters and nuclear-pumped lasers, physics of compact

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

Crossroads: Quality of Life in a Nuclear World. A High School English Curriculum.

ERIC Educational Resources Information Center

French, Dan; And Others

One of a set of high school curricula on nuclear issues, this 10-day unit for English classes informs students of the issues surrounding the nuclear arms race and military spending. Each lesson includes readings, worksheets, and a daily homework assignment and focuses on one of the following activities: discussion, brainstorming, role playing, or…

Elevated nuclear sphingoid base-1-phosphates and decreased histone deacetylase activity after fumonisin B1 treatment in mouse embryonic fibroblasts

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

Gardner, Nicole M., E-mail: nicolegardner@creighton.edu; Riley, Ronald T.; Showker, Jency L.

Fumonisin B1 (FB1) is a mycotoxin produced by a common fungal contaminant of corn. Administration of FB1 to pregnant LM/Bc mice induces exencephaly in embryos, and ingestion of FB1-contaminated food during early pregnancy is associated with increased risk for neural tube defects (NTDs) in humans. FB1 inhibits ceramide synthase enzymes in sphingolipid biosynthesis, causing sphinganine (Sa) and bioactive sphinganine-1-phosphate (Sa1P) accumulation in blood, cells, and tissues. Sphingosine kinases (Sphk) phosphorylate Sa to form Sa1P. Upon activation, Sphk1 associates primarily with the plasma membrane, while Sphk2 is found predominantly in the nucleus. In cells over-expressing Sphk2, accumulation of Sa1P in themore » nuclear compartment inhibits histone deacetylase (HDAC) activity, causing increased acetylation of histone lysine residues. In this study, FB1 treatment in LM/Bc mouse embryonic fibroblasts (MEFs) resulted in significant accumulation of Sa1P in nuclear extracts relative to cytoplasmic extracts. Elevated nuclear Sa1P corresponded to decreased histone deacetylase (HDAC) activity and increased histone acetylation at H2BK12, H3K9, H3K18, and H3K23. Treatment of LM/Bc MEFs with a selective Sphk1 inhibitor, PF-543, or with ABC294640, a selective Sphk2 inhibitor, significantly reduced nuclear Sa1P accumulation after FB1, although Sa1P levels remained significantly increased relative to basal levels. Concurrent treatment with both PF-543 and ABC294640 prevented nuclear accumulation of Sa1P in response to FB1. Other HDAC inhibitors are known to cause NTDs, so these results suggest that FB1-induced disruption of sphingolipid metabolism leading to nuclear Sa1P accumulation, HDAC inhibition, and histone hyperacetylation is a potential mechanism for FB1-induced NTDs. - Highlights: • FB1 treatment results in accumulation of Sa1P primarily in the nucleus of MEFs. • FB1 treatment and elevated nuclear Sa1P are associated with HDAC inhibition. • Sphk2 inhibition

THE NUCLEAR ACTIVITIES OF NEARBY S0 GALAXIES

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

Xiao, Meng-Yuan; Gu, Qiu-Sheng; Chen, Yan-Mei

2016-11-01

We present a study of nuclear activities in nearby S0 galaxies. After cross-matching the Sloan Digital Sky Survey Data Release 7 with the Third Reference Catalog of Bright Galaxies (RC3) and visually checking the SDSS images, we derive a sample of 583 S0 galaxies with the central spectrophotometric information. In order to separate nebular emission lines from the underlying stellar contribution, we fit the stellar population model to the SDSS spectra of these S0 galaxies. According to the BPT diagram, we find that 8% of S0 galaxies show central star-forming activity, while the fractions of Seyfert, Composite, and low-ionization nuclearmore » emission-line regions (LINERs) are 2%, 8%, and 21.4%, respectively. We also find that star-forming S0s have the lowest stellar masses, over one magnitude lower than the others, and that the active S0s are mainly located in the sparse environment, while the normal S0s are located in the dense environment, which might suggest that the environment plays an important role in quenching star formation and/or AGN activity in S0 galaxies. By performing bulge-disk decomposition of 45 star-forming S0s in g - and r -bands with the 2D fitting software Galfit, as well as exploiting the catalog of 2D photometric decompositions of Meert et al., we find that the bulges of approximately one-third of star-forming S0 galaxies (16/45) are bluer than their disks, while for other types of S0s the bulge and disk components show similar color distributions. Besides, the Sérsic index of most star-forming S0s bulges is less than two, while for normal S0s, it is between two and six.« less

Enhancing Efficiency of Safeguards at Facilities that are Shutdown or Closed-Down, including those being Decommissioned

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

Moran, B.; Stern, W.; Colley, J.

International Atomic Energy Agency (IAEA) safeguards involves verification activities at a wide range of facilities in a variety of operational phases (e.g., under construction, start-up, operating, shutdown, closed-down, and decommissioned). Safeguards optimization for each different facility type and operational phase is essential for the effectiveness of safeguards implementation. The IAEA’s current guidance regarding safeguards for the different facility types in the various lifecycle phases is provided in its Design Information Examination (DIE) and Verification (DIV) procedure. 1 Greater efficiency in safeguarding facilities that are shut down or closed down, including those being decommissioned, could allow the IAEA to use amore » greater portion of its effort to conduct other verification activities. Consequently, the National Nuclear Security Administration’s Office of International Nuclear Safeguards sponsored this study to evaluate whether there is an opportunity to optimize safeguards approaches for facilities that are shutdown or closed-down. The purpose of this paper is to examine existing safeguards approaches for shutdown and closed-down facilities, including facilities being decommissioned, and to seek to identify whether they may be optimized.« less

Nuclear Factor Kappa B Activation Occurs in the Amnion Prior to Labour Onset and Modulates the Expression of Numerous Labour Associated Genes

PubMed Central

Lim, Sheri; MacIntyre, David A.; Lee, Yun S.; Khanjani, Shirin; Terzidou, Vasso; Teoh, T. G.; Bennett, Phillip R.

2012-01-01

Background Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFκB). In this study we characterised the level of NFκB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour. Methodology/Principal Findings We found that a proportion of women exhibit low or moderate NFκB activity while other women exhibit high levels of NFκB activity (n = 12). This activation process does not appear to involve classical pathways of NFκB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised non-activated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryonic development and tissue development. Conclusions/Significance Our results indicate that assessment of amnion NFκB activation is critical for accurate sample classification and subsequent interpretation of data. Collectively, our data suggest amnion activation is largely an inflammatory event that occurs in the amnion epithelial layer as a prelude to the onset of labour. PMID:22485186

Factors affecting the development of somatic cell nuclear transfer embryos in Cattle.

PubMed

Akagi, Satoshi; Matsukawa, Kazutsugu; Takahashi, Seiya

2014-01-01

Nuclear transfer is a complex multistep procedure that includes oocyte maturation, cell cycle synchronization of donor cells, enucleation, cell fusion, oocyte activation and embryo culture. Therefore, many factors are believed to contribute to the success of embryo development following nuclear transfer. Numerous attempts to improve cloning efficiency have been conducted since the birth of the first sheep by somatic cell nuclear transfer. However, the efficiency of somatic cell cloning has remained low, and applications have been limited. In this review, we discuss some of the factors that affect the developmental ability of somatic cell nuclear transfer embryos in cattle.

Factors Affecting the Development of Somatic Cell Nuclear Transfer Embryos in Cattle

PubMed Central

AKAGI, Satoshi; MATSUKAWA, Kazutsugu; TAKAHASHI, Seiya

2014-01-01

Nuclear transfer is a complex multistep procedure that includes oocyte maturation, cell cycle synchronization of donor cells, enucleation, cell fusion, oocyte activation and embryo culture. Therefore, many factors are believed to contribute to the success of embryo development following nuclear transfer. Numerous attempts to improve cloning efficiency have been conducted since the birth of the first sheep by somatic cell nuclear transfer. However, the efficiency of somatic cell cloning has remained low, and applications have been limited. In this review, we discuss some of the factors that affect the developmental ability of somatic cell nuclear transfer embryos in cattle. PMID:25341701

Stress-specific p38 MAPK activation is sufficient to drive EGFR endocytosis but not its nuclear translocation.

PubMed

Tomas, Alejandra; Jones, Sylwia; Vaughan, Simon O; Hochhauser, Daniel; Futter, Clare E

2017-08-01

EGF receptor (EGFR) endocytosis is induced by stress in a manner dependent on the p38 MAPK family. Ligand and stresses such as X-rays, reportedly promote nuclear trafficking of endocytosed EGFR for regulation of gene transcription and DNA repair. We fail to detect EGFR endocytosis or nuclear transport following X-ray treatment of HeLa or head and neck cancer cells, despite extensive DNA damage induction. Apparent nuclear staining with EGFR extracellular domain antibody remained present despite reduced/absent EGFR expression, and so did not represent nuclear EGFR. UVB and UVC, but not X-ray or UVA, treatment induced p38 activation and EGFR endocytosis, although all of these stresses induced DNA damage, indicating that DNA damage alone is not sufficient to induce EGFR endocytosis. Increased reactive oxygen species (ROS) levels following UVB treatment, compared to that seen with X-rays, do not alone explain differences in p38 activation. UVB, like UVC, induced EGFR accumulation predominantly in perinuclear endosomes, rather than in the nucleus. Our morphological techniques identifying major changes in receptor distribution do not exclude the possibility that small but biologically relevant amounts of EGFR enter the nucleus. This study highlights the importance and limitations of morphological analyses of receptor distribution in understanding signaling outcome. © 2017. Published by The Company of Biologists Ltd.

Moving Cell Boundaries Drive Nuclear Shaping during Cell Spreading.

PubMed

Li, Yuan; Lovett, David; Zhang, Qiao; Neelam, Srujana; Kuchibhotla, Ram Anirudh; Zhu, Ruijun; Gundersen, Gregg G; Lele, Tanmay P; Dickinson, Richard B

2015-08-18

The nucleus has a smooth, regular appearance in normal cells, and its shape is greatly altered in human pathologies. Yet, how the cell establishes nuclear shape is not well understood. We imaged the dynamics of nuclear shaping in NIH3T3 fibroblasts. Nuclei translated toward the substratum and began flattening during the early stages of cell spreading. Initially, nuclear height and width correlated with the degree of cell spreading, but over time, reached steady-state values even as the cell continued to spread. Actomyosin activity, actomyosin bundles, microtubules, and intermediate filaments, as well as the LINC complex, were all dispensable for nuclear flattening as long as the cell could spread. Inhibition of actin polymerization as well as myosin light chain kinase with the drug ML7 limited both the initial spreading of cells and flattening of nuclei, and for well-spread cells, inhibition of myosin-II ATPase with the drug blebbistatin decreased cell spreading with associated nuclear rounding. Together, these results show that cell spreading is necessary and sufficient to drive nuclear flattening under a wide range of conditions, including in the presence or absence of myosin activity. To explain this observation, we propose a computational model for nuclear and cell mechanics that shows how frictional transmission of stress from the moving cell boundaries to the nuclear surface shapes the nucleus during early cell spreading. Our results point to a surprisingly simple mechanical system in cells for establishing nuclear shapes. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Regulation of Liver Energy Balance by the Nuclear Receptors Farnesoid X Receptor and Peroxisome Proliferator Activated Receptor α.

PubMed

Kim, Kang Ho; Moore, David D

2017-01-01

The liver undergoes major changes in substrate utilization and metabolic output over the daily feeding and fasting cycle. These changes occur acutely in response to hormones such as insulin and glucagon, with rapid changes in signaling pathways mediated by protein phosphorylation and other post-translational modifications. They are also reflected in chronic alterations in gene expression in response to nutrient-sensitive transcription factors. Among these, the nuclear receptors farnesoid X receptor (FXR) and peroxisome proliferator activated receptor α (PPARα) provide an intriguing, coordinated response to maintain energy balance in the liver. FXR is activated in the fed state by bile acids returning to the liver, while PPARα is activated in the fasted state in response to the free fatty acids produced by adipocyte lipolysis or possibly other signals. Key Messages: Previous studies indicate that FXR and PPARα have opposing effects on each other's primary targets in key metabolic pathways including gluconeogenesis. Our more recent work shows that these 2 nuclear receptors coordinately regulate autophagy: FXR suppresses this pathway of nutrient and energy recovery, while PPARα activates it. Another recent study indicates that FXR activates the complement and coagulation pathway, while earlier studies identify this as a negative target of PPARα. Since secretion is a very energy- and nutrient-intensive process for hepatocytes, it is possible that FXR licenses it in the nutrient-rich fed state, while PPARα represses it to spare resources in the fasted state. Energy balance is a potential connection linking FXR and PPARα regulation of autophagy and secretion, 2 seemingly unrelated aspects of hepatocyte function. FXR and PPARα act coordinately to promote energy balance and homeostasis in the liver by regulating autophagy and potentially protein secretion. It is quite likely that their impact extends to additional pathways relevant to hepatic energy balance, and

Integral nuclear data validation using experimental spent nuclear fuel compositions

DOE PAGES

Gauld, Ian C.; Williams, Mark L.; Michel-Sendis, Franco; ...

2017-07-19

Measurements of the isotopic contents of spent nuclear fuel provide experimental data that are a prerequisite for validating computer codes and nuclear data for many spent fuel applications. Under the auspices of the Organisation for Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) and guidance of the Expert Group on Assay Data of Spent Nuclear Fuel of the NEA Working Party on Nuclear Criticality Safety, a new database of expanded spent fuel isotopic compositions has been compiled. The database, Spent Fuel Compositions (SFCOMPO) 2.0, includes measured data for more than 750 fuel samples acquired from 44 different reactors andmore » representing eight different reactor technologies. Measurements for more than 90 isotopes are included. This new database provides data essential for establishing the reliability of code systems for inventory predictions, but it also has broader potential application to nuclear data evaluation. Furthermore, the database, together with adjoint based sensitivity and uncertainty tools for transmutation systems developed to quantify the importance of nuclear data on nuclide concentrations, are described.« less

Integral nuclear data validation using experimental spent nuclear fuel compositions

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

Gauld, Ian C.; Williams, Mark L.; Michel-Sendis, Franco

Measurements of the isotopic contents of spent nuclear fuel provide experimental data that are a prerequisite for validating computer codes and nuclear data for many spent fuel applications. Under the auspices of the Organisation for Economic Co-operation and Development (OECD) Nuclear Energy Agency (NEA) and guidance of the Expert Group on Assay Data of Spent Nuclear Fuel of the NEA Working Party on Nuclear Criticality Safety, a new database of expanded spent fuel isotopic compositions has been compiled. The database, Spent Fuel Compositions (SFCOMPO) 2.0, includes measured data for more than 750 fuel samples acquired from 44 different reactors andmore » representing eight different reactor technologies. Measurements for more than 90 isotopes are included. This new database provides data essential for establishing the reliability of code systems for inventory predictions, but it also has broader potential application to nuclear data evaluation. Furthermore, the database, together with adjoint based sensitivity and uncertainty tools for transmutation systems developed to quantify the importance of nuclear data on nuclide concentrations, are described.« 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.

Nuclear-Localized and Deregulated Calcium- and Calmodulin-Dependent Protein Kinase Activates Rhizobial and Mycorrhizal Responses in Lotus japonicus[W

PubMed Central

Takeda, Naoya; Maekawa, Takaki; Hayashi, Makoto

2012-01-01

The common symbiosis pathway is at the core of symbiosis signaling between plants and soil microbes. In this pathway, calcium- and calmodulin-dependent protein kinase (CCaMK) plays a crucial role in integrating the signals both in arbuscular mycorrhizal symbiosis (AMS) and in root nodule symbiosis (RNS). However, the molecular mechanism by which CCaMK coordinates AMS and RNS is largely unknown. Here, we report that the gain-of-function (GOF) variants of CCaMK without the regulatory domains activate both AMS and RNS signaling pathways in the absence of symbiotic partners. This activation requires nuclear localization of CCaMK. Enforced nuclear localization of the GOF-CCaMK variants by fusion with a canonical nuclear localization signal enhances signaling activity of AMS and RNS. The GOF-CCaMK variant triggers formation of a structure similar to the prepenetration apparatus, which guides infection of arbuscular mycorrhizal fungi to host root cells. In addition, the GOF-CCaMK variants without the regulatory domains partly restore AMS but fail to support rhizobial infection in ccamk mutants. These data indicate that AMS, the more ancient type of symbiosis, can be mainly regulated by the kinase activity of CCaMK, whereas RNS, which evolved more recently, requires complex regulation performed by the regulatory domains of CCaMK. PMID:22337918

Interaction of Yna1 and Yna2 Is Required for Nuclear Accumulation and Transcriptional Activation of the Nitrate Assimilation Pathway in the Yeast Hansenula polymorpha.

PubMed

Silvestrini, Lucia; Rossi, Beatrice; Gallmetzer, Andreas; Mathieu, Martine; Scazzocchio, Claudio; Berardi, Enrico; Strauss, Joseph

2015-01-01

A few yeasts, including Hansenula polymorpha are able to assimilate nitrate and use it as nitrogen source. The genes necessary for nitrate assimilation are organised in this organism as a cluster comprising those encoding nitrate reductase (YNR1), nitrite reductase (YNI1), a high affinity transporter (YNT1), as well as the two pathway specific Zn(II)2Cys2 transcriptional activators (YNA1, YNA2). Yna1p and Yna2p mediate induction of the system and here we show that their functions are interdependent. Yna1p activates YNA2 as well as its own (YNA1) transcription thus forming a nitrate-dependent autoactivation loop. Using a split-YFP approach we demonstrate here that Yna1p and Yna2p form a heterodimer independently of the inducer and despite both Yna1p and Yna2p can occupy the target promoter as mono- or homodimer individually, these proteins are transcriptionally incompetent. Subsequently, the transcription factors target genes containing a conserved DNA motif (termed nitrate-UAS) determined in this work by in vitro and in vivo protein-DNA interaction studies. These events lead to a rearrangement of the chromatin landscape on the target promoters and are associated with the onset of transcription of these target genes. In contrast to other fungi and plants, in which nuclear accumulation of the pathway-specific transcription factors only occur in the presence of nitrate, Yna1p and Yna2p are constitutively nuclear in H. polymorpha. Yna2p is needed for this nuclear accumulation and Yna1p is incapable of strictly positioning in the nucleus without Yna2p. In vivo DNA footprinting and ChIP analyses revealed that the permanently nuclear Yna1p/Yna2p heterodimer only binds to the nitrate-UAS when the inducer is present. The nitrate-dependent up-regulation of one partner protein in the heterodimeric complex is functionally similar to the nitrate-dependent activation of nuclear accumulation in other systems.

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

Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila

PubMed Central

Li, Qian; Zhang, Xuchen; Liang, Xitong; Zhang, Fang; Wang, Lianzhang; Zhong, Yi

2016-01-01

Translocation of signaling molecules, MAPK in particular, from the cytosol to nucleus represents a universal key element in initiating the gene program that determines memory consolidation. Translocation mechanisms and their behavioral impact, however, remain to be determined. Here, we report that a highly conserved nuclear transporter, Drosophila importin-7 (DIM-7), regulates import of training-activated MAPK for consolidation of long-term memory (LTM). We show that silencing DIM-7 functions results in impaired LTM, whereas overexpression of DIM-7 enhances LTM. This DIM-7–dependent regulation of LTM is confined to a consolidation time window and in mushroom body neurons. Image data show that bidirectional alteration in DIM-7 expression results in proportional changes in the intensity of training-activated MAPK accumulated within the nuclei of mushroom body neurons during LTM consolidation. Such DIM-7–regulated nuclear accumulation of activated MAPK is observed only in the training specified for LTM induction and determines the amplitude, but not the time course, of memory consolidation. PMID:26929354

Nuclear Scans

MedlinePlus

Nuclear scans use radioactive substances to see structures and functions inside your body. They use a special ... images. Most scans take 20 to 45 minutes. Nuclear scans can help doctors diagnose many conditions, including ...

Space Nuclear Thermal Propulsion (SNTP) Air Force facility

NASA Technical Reports Server (NTRS)

Beck, David F.

1993-01-01

The Space Nuclear Thermal Propulsion (SNTP) Program is an initiative within the US Air Force to acquire and validate advanced technologies that could be used to sustain superior capabilities in the area or space nuclear propulsion. The SNTP Program has a specific objective of demonstrating the feasibility of the particle bed reactor (PBR) concept. The term PIPET refers to a project within the SNTP Program responsible for the design, development, construction, and operation of a test reactor facility, including all support systems, that is intended to resolve program technology issues and test goals. A nuclear test facility has been designed that meets SNTP Facility requirements. The design approach taken to meet SNTP requirements has resulted in a nuclear test facility that should encompass a wide range of nuclear thermal propulsion (NTP) test requirements that may be generated within other programs. The SNTP PIPET project is actively working with DOE and NASA to assess this possibility.

The Department of Energy Nuclear Criticality Safety Program

NASA Astrophysics Data System (ADS)

Felty, James R.

2005-05-01

This paper broadly covers key events and activities from which the Department of Energy Nuclear Criticality Safety Program (NCSP) evolved. The NCSP maintains fundamental infrastructure that supports operational criticality safety programs. This infrastructure includes continued development and maintenance of key calculational tools, differential and integral data measurements, benchmark compilation, development of training resources, hands-on training, and web-based systems to enhance information preservation and dissemination. The NCSP was initiated in response to Defense Nuclear Facilities Safety Board Recommendation 97-2, Criticality Safety, and evolved from a predecessor program, the Nuclear Criticality Predictability Program, that was initiated in response to Defense Nuclear Facilities Safety Board Recommendation 93-2, The Need for Critical Experiment Capability. This paper also discusses the role Dr. Sol Pearlstein played in helping the Department of Energy lay the foundation for a robust and enduring criticality safety infrastructure.

Application of the Monte Carlo method to estimate doses due to neutron activation of different materials in a nuclear reactor

NASA Astrophysics Data System (ADS)

Ródenas, José

2017-11-01

All materials exposed to some neutron flux can be activated independently of the kind of the neutron source. In this study, a nuclear reactor has been considered as neutron source. In particular, the activation of control rods in a BWR is studied to obtain the doses produced around the storage pool for irradiated fuel of the plant when control rods are withdrawn from the reactor and installed into this pool. It is very important to calculate these doses because they can affect to plant workers in the area. The MCNP code based on the Monte Carlo method has been applied to simulate activation reactions produced in the control rods inserted into the reactor. Obtained activities are introduced as input into another MC model to estimate doses produced by them. The comparison of simulation results with experimental measurements allows the validation of developed models. The developed MC models have been also applied to simulate the activation of other materials, such as components of a stainless steel sample introduced into a training reactors. These models, once validated, can be applied to other situations and materials where a neutron flux can be found, not only nuclear reactors. For instance, activation analysis with an Am-Be source, neutrography techniques in both medical applications and non-destructive analysis of materials, civil engineering applications using a Troxler, analysis of materials in decommissioning of nuclear power plants, etc.

Plants as sources of airborne bacteria, including ice nucleation-active bacteria.

PubMed

Lindemann, J; Constantinidou, H A; Barchet, W R; Upper, C D

1982-11-01

Vertical wind shear and concentration gradients of viable, airborne bacteria were used to calculate the upward flux of viable cells above bare soil and canopies of several crops. Concentrations at soil or canopy height varied from 46 colony-forming units per m over young corn and wet soil to 663 colony-forming units per m over dry soil and 6,500 colony-forming units per m over a closed wheat canopy. In simultaneous samples, concentrations of viable bacteria in the air 10 m inside an alfalfa field were fourfold higher than those over a field with dry, bare soil immediately upwind. The upward flux of viable bacteria over alfalfa was three- to fourfold greater than over dry soil. Concentrations of ice nucleation-active bacteria were higher over plants than over soil. Thus, plant canopies may constitute a major source of bacteria, including ice nucleation-active bacteria, in the air.

Keap1 silencing boosts lipopolysaccharide-induced transcription of interleukin 6 via activation of nuclear factor κB in macrophages

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

Lv, Peng; Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709; Xue, Peng

2013-11-01

Interleukin-6 (IL6) is a multifunctional cytokine that regulates immune and inflammatory responses. Multiple transcription factors, including nuclear factor κB (NF-κB) and nuclear factor E2-related factor 2 (Nrf2), regulate IL6 transcription. Kelch-like ECH-associated protein 1 (Keap1) is a substrate adaptor protein for the Cullin 3-dependent E3 ubiquitin ligase complex, which regulates the degradation of many proteins, including Nrf2 and IκB kinase β (IKKβ). Here, we found that stable knockdown of Keap1 (Keap1-KD) in RAW 264.7 (RAW) mouse macrophages and human monocyte THP-1 cells significantly increased expression of Il6, and Nrf2-target genes, under basal and lipopolysaccharide (LPS, 0.001–0.1 μg/ml)-challenged conditions. However, Nrf2more » activation alone, by tert-butylhydroquinone treatment of RAW cells, did not increase expression of Il6. Compared to cells transduced with scrambled non-target negative control shRNA, Keap1-KD RAW cells showed enhanced protein levels of IKKβ and increased expression and phosphorylation of NF-κB p65 under non-stressed and LPS-treated conditions. Because the expression of Il6 in Keap1-KD RAW cells was significantly attenuated by silencing of Ikkβ, but not Nrf2, it appears that stabilized IKKβ is responsible for the enhanced transactivation of Il6 in Keap1-KD cells. This study demonstrated that silencing of Keap1 in macrophages boosts LPS-induced transcription of Il6 via NF-κB activation. Given the importance of IL6 in the inflammatory response, the Keap1–IKKβ–NF-κB pathway may be a novel target for treatment and prevention of inflammation and associated disorders. - Highlights: • Knockdown of Keap1 increases expression of Il6 in macrophages. • Silencing of Keap1 results in protein accumulation of IKKβ and NF-κB p65. • Induction of Il6 resulting from Keap1 silencing is attributed to NF-κB activation.« less

Summer Schools in Nuclear and Radiochemistry

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

Silber, Herbert B.

The ACS Summer Schools in Nuclear and Radiochemistry (herein called “Summer Schools”) were funded by the U.S. Department of Energy and held at San Jose State University (SJSU) and Brookhaven National Laboratory (BNL). The Summer Schools offer undergraduate students with U.S. citizenship an opportunity to complete coursework through ACS accredited chemistry degree programs at SJSU or the State University of New York at Stony Brook (SBU). The courses include lecture and laboratory work on the fundamentals and applications of nuclear and radiochemistry. The number of students participating at each site is limited to 12, and the low student-to-instructor ratio ismore » needed due to the intense nature of the six-week program. To broaden the students’ perspectives on nuclear science, prominent research scientists active in nuclear and/or radiochemical research participate in a Guest Lecture Series. Symposia emphasizing environmental chemistry, nuclear medicine, and career opportunities are conducted as a part of the program. The Department of Energy’s Office of Basic Energy Sciences (BES) renewed the five-year proposal for the Summer Schools starting March 1, 2007, with contributions from Biological and Environmental Remediation (BER) and Nuclear Physics (NP). This Final Technical Report covers the Summer Schools held in the years 2007-2011.« less

[Effectiveness of mental health training including active listening for managers].

PubMed

Ikegami, Kazunori; Tagawa, Yoshimasa; Mafune, Kosuke; Hiro, Hisanori; Nagata, Shoji

2008-07-01

significant increases post-training in "Job demands", "Worksite support by supervisor" and "Worksite support by co-worker", subscales of the BJSQ 12 items version. Particularly, the "Worksite support by supervisor" subscale increased significantly in 8 of the 47 sections in a comparison among sections. In this present study, we investigated the effectiveness of mental health training including Active Listening for managers, and suggest that to train Active Listening and use it at the worksite possibly strengthens "Worksite support by supervisor".

Nuclear Glycolytic Enzyme Enolase of Toxoplasma gondii Functions as a Transcriptional Regulator

PubMed Central

Mouveaux, Thomas; Oria, Gabrielle; Werkmeister, Elisabeth; Slomianny, Christian; Fox, Barbara A.; Bzik, David J.; Tomavo, Stanislas

2014-01-01

Apicomplexan parasites including Toxoplasma gondii have complex life cycles within different hosts and their infectivity relies on their capacity to regulate gene expression. However, little is known about the nuclear factors that regulate gene expression in these pathogens. Here, we report that T. gondii enolase TgENO2 is targeted to the nucleus of actively replicating parasites, where it specifically binds to nuclear chromatin in vivo. Using a ChIP-Seq technique, we provide evidence for TgENO2 enrichment at the 5′ untranslated gene regions containing the putative promoters of 241 nuclear genes. Ectopic expression of HA-tagged TgENO1 or TgENO2 led to changes in transcript levels of numerous gene targets. Targeted disruption of TgENO1 gene results in a decrease in brain cyst burden of chronically infected mice and in changes in transcript levels of several nuclear genes. Complementation of this knockout mutant with ectopic TgENO1-HA fully restored normal transcript levels. Our findings reveal that enolase functions extend beyond glycolytic activity and include a direct role in coordinating gene regulation in T. gondii. PMID:25153525

The Off-Site Plowshare and Vela Uniform Programs: Assessing Potential Environmental Liabilities through an Examination of Proposed Nuclear Projects,High Explosive Experiments, and High Explosive Construction Activities Volume 1 of 3

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

Beck Colleen M,Edwards Susan R.,King Maureen L.

2011-09-01

This document presents the results of nearly six years (2002-2008) of historical research and field studies concerned with evaluating potential environmental liabilities associated with U.S. Atomic Energy Commission projects from the Plowshare and Vela Uniform Programs. The Plowshare Program's primary purpose was to develop peaceful uses for nuclear explosives. The Vela Uniform Program focused on improving the capability of detecting, monitoring and identifying underground nuclear detonations. As a result of the Project Chariot site restoration efforts in the early 1990s, there were concerns that there might be other project locations with potential environmental liabilities. The Desert Research Institute conducted archivalmore » research to identify projects, an analysis of project field activities, and completed field studies at locations where substantial fieldwork had been undertaken for the projects. Although the Plowshare and Vela Uniform nuclear projects are well known, the projects that are included in this research are relatively unknown. They are proposed nuclear projects that were not executed, proposed and executed high explosive experiments, and proposed and executed high explosive construction activities off the Nevada Test Site. The research identified 170 Plowshare and Vela Uniform off-site projects and many of these had little or no field activity associated with them. However, there were 27 projects that merited further investigation and field studies were conducted at 15 locations.« less

The Off-Site Plowshare and Vela Uniform Programs: Assessing Potential Environmental Liabilities through an Examination of Proposed Nuclear Projects,High Explosive Experiments, and High Explosive Construction Activities Volume 3 of 3

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

Beck Colleen M.,Edwards Susan R.,King Maureen L.

2011-09-01

This document presents the results of nearly six years (2002-2008) of historical research and field studies concerned with evaluating potential environmental liabilities associated with U.S. Atomic Energy Commission projects from the Plowshare and Vela Uniform Programs. The Plowshare Program's primary purpose was to develop peaceful uses for nuclear explosives. The Vela Uniform Program focused on improving the capability of detecting, monitoring and identifying underground nuclear detonations. As a result of the Project Chariot site restoration efforts in the early 1990s, there were concerns that there might be other project locations with potential environmental liabilities. The Desert Research Institute conducted archivalmore » research to identify projects, an analysis of project field activities, and completed field studies at locations where substantial fieldwork had been undertaken for the projects. Although the Plowshare and Vela Uniform nuclear projects are well known, the projects that are included in this research are relatively unknown. They are proposed nuclear projects that were not executed, proposed and executed high explosive experiments, and proposed and executed high explosive construction activities off the Nevada Test Site. The research identified 170 Plowshare and Vela Uniform off-site projects and many of these had little or no field activity associated with them. However, there were 27 projects that merited further investigation and field studies were conducted at 15 locations.« less

The Off-Site Plowshare and Vela Uniform Programs: Assessing Potential Environmental Liabilities through an Examination of Proposed Nuclear Projects,High Explosive Experiments, and High Explosive Construction Activities Volume 2 of 3

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

Beck Colleen M.,Edwards Susan R.,King Maureen L.

2011-09-01

This document presents the results of nearly six years (2002-2008) of historical research and field studies concerned with evaluating potential environmental liabilities associated with U.S. Atomic Energy Commission projects from the Plowshare and Vela Uniform Programs. The Plowshare Program's primary purpose was to develop peaceful uses for nuclear explosives. The Vela Uniform Program focused on improving the capability of detecting, monitoring and identifying underground nuclear detonations. As a result of the Project Chariot site restoration efforts in the early 1990s, there were concerns that there might be other project locations with potential environmental liabilities. The Desert Research Institute conducted archivalmore » research to identify projects, an analysis of project field activities, and completed field studies at locations where substantial fieldwork had been undertaken for the projects. Although the Plowshare and Vela Uniform nuclear projects are well known, the projects that are included in this research are relatively unknown. They are proposed nuclear projects that were not executed, proposed and executed high explosive experiments, and proposed and executed high explosive construction activities off the Nevada Test Site. The research identified 170 Plowshare and Vela Uniform off-site projects and many of these had little or no field activity associated with them. However, there were 27 projects that merited further investigation and field studies were conducted at 15 locations.« less

Nuclear Forensics: A Methodology Applicable to Nuclear Security and to Non-Proliferation

NASA Astrophysics Data System (ADS)

Mayer, K.; Wallenius, M.; Lützenkirchen, K.; Galy, J.; Varga, Z.; Erdmann, N.; Buda, R.; Kratz, J.-V.; Trautmann, N.; Fifield, K.

2011-09-01

Nuclear Security aims at the prevention and detection of and response to, theft, sabotage, unauthorized access, illegal transfer or other malicious acts involving nuclear material. Nuclear Forensics is a key element of nuclear security. Nuclear Forensics is defined as a methodology that aims at re-establishing the history of nuclear material of unknown origin. It is based on indicators that arise from known relationships between material characteristics and process history. Thus, nuclear forensics analysis includes the characterization of the material and correlation with production history. To this end, we can make use of parameters such as the isotopic composition of the nuclear material and accompanying elements, chemical impurities, macroscopic appearance and microstructure of the material. In the present paper, we discuss the opportunities for attribution of nuclear material offered by nuclear forensics as well as its limitations. Particular attention will be given to the role of nuclear reactions. Such reactions include the radioactive decay of the nuclear material, but also reactions with neutrons. When uranium (of natural composition) is exposed to neutrons, plutonium is formed, as well as 236U. We will illustrate the methodology using the example of a piece of uranium metal that dates back to the German nuclear program in the 1940's. A combination of different analytical techniques and model calculations enables a nuclear forensics interpretation, thus correlating the material characteristics with the production history.

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.

The Future of Energy from Nuclear Fission

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

Kim, Son H.; Taiwo, Temitope

Nuclear energy is an important part of our current global energy system, and contributes to supplying the significant demand for electricity for many nations around the world. There are 433 commercial nuclear power reactors operating in 30 countries with an installed capacity of 367 GWe as of October 2011 (IAEA PRIS, 2011). Nuclear electricity generation totaled 2630 TWh in 2010 representing 14% the world’s electricity generation. The top five countries of total installed nuclear capacity are the US, France, Japan, Russia and South Korea at 102, 63, 45, 24, and 21 GWe, respectively (WNA, 2012a). The nuclear capacity of thesemore » five countries represents more than half, 68%, of the total global nuclear capacity. The role of nuclear power in the global energy system today has been motivated by several factors including the growing demand for electric power, the regional availability of fossil resources and energy security concerns, and the relative competitiveness of nuclear power as a source of base-load electricity. There is additional motivation for the use of nuclear power because it does not produce greenhouse gas (GHG) emissions or local air pollutants during its operation and contributes to low levels of emissions throughout the lifecycle of the nuclear energy system (Beerten, J. et. al., 2009). Energy from nuclear fission primarily in the form of electric power and potentially as a source of industrial heat could play a greater role for meeting the long-term growing demand for energy worldwide while addressing the concern for climate change from rising GHG emissions. However, the nature of nuclear fission as a tremendously compact and dense form of energy production with associated high concentrations of radioactive materials has particular and unique challenges as well as benefits. These challenges include not only the safety and cost of nuclear reactors, but proliferation concerns, safeguard and storage of nuclear materials associated with nuclear

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.

Nuclear Explosion Monitoring History and Research and Development

NASA Astrophysics Data System (ADS)

Hawkins, W. L.; Zucca, J. J.

2008-12-01

Within a year after the nuclear detonations over Hiroshima and Nagasaki the Baruch Plan was presented to the newly formed United Nations Atomic Energy Commission (June 14, 1946) to establish nuclear disarmament and international control over all nuclear activities. These controls would allow only the peaceful use of atomic energy. The plan was rejected through a Security Council veto primarily because of the resistance to unlimited inspections. Since that time there have been many multilateral, and bilateral agreements, and unilateral declarations to limit or eliminate nuclear detonations. Almost all of theses agreements (i.e. treaties) call for some type of monitoring. We will review a timeline showing the history of nuclear testing and the more important treaties. We will also describe testing operations, containment, phenomenology, and observations. The Comprehensive Nuclear Test Ban Treaty (CTBT) which has been signed by 179 countries (ratified by 144) established the International Monitoring System global verification regime which employs seismic, infrasound, hydroacoustic and radionuclide monitoring techniques. The CTBT also includes on-site inspection to clarify whether a nuclear explosion has been carried out in violation of the Treaty. The US Department of Energy (DOE) through its National Nuclear Security Agency's Ground-Based Nuclear Explosion Monitoring R&D Program supports research by US National Laboratories, and universities and industry internationally to detect, locate, and identify nuclear detonations. This research program builds on the broad base of monitoring expertise developed over several decades. Annually the DOE and the US Department of Defense jointly solicit monitoring research proposals. Areas of research include: seismic regional characterization and wave propagation, seismic event detection and location, seismic identification and source characterization, hydroacoustic monitoring, radionuclide monitoring, infrasound monitoring, and

Dedifferentiated liposarcoma with homologous lipoblastic differentiation: expanding the spectrum to include low-grade tumours.

PubMed

Liau, Jau-Yu; Lee, Jen-Chieh; Wu, Chen-Tu; Kuo, Kuan-Ting; Huang, Hsuan-Ying; Liang, Cher-Wei

2013-04-01

Dedifferentiated liposarcoma (DDLPS) is traditionally defined as a non-lipogenic high-grade sarcoma arising from a well-differentiated liposarcoma that confers metastatic potential. Recently, DDLPSs with lipoblastic differentiation, i.e. morphologically lipogenic DDLPSs, were reported. Because of the lipoblastic differentiation, these tumours caused confusion, and were reported under different names. However, cytogenetic and molecular studies have revealed their DDLPS nature. So far, the cases reported have been high-grade pleomorphic liposarcoma-like tumours. In this study we have collected another series that contains low-grade tumours, and expand the histological spectrum. Eighteen cases of DDLPS with lipoblastic differentiation from various anatomical locations were analysed by routine histology, immunohistochemistry, and MDM2 fluorescence in-situ hybridization. Two main histological patterns were seen: one featured a spindle cell sarcoma containing lipoblasts with variable nuclear pleomorphism, and the other a pleomorphic liposarcoma-like tumour including the epithelioid variant. Two cases showed low nuclear grade and lipogenic activity in the metastatic foci. CDK4, MDM2 and p16(INK) (4a) overexpression was seen in all except one case. MDM2 amplification was found in all 16 cases tested. We have expanded the spectrum of this variant of DDLPS to include low-grade tumours, in which a careful search for increased mitotic activity is essential. Like conventional DDLPS, these tumours are capable of metastasis. © 2012 Blackwell Publishing Ltd.

[The bioelectric activity of the brain in dyscirculatory encephalopathy and arterial hypertension developed in the Chernobyl nuclear disaster liquidators].

PubMed

Podsonnaia, I V; Efremushkin, G G; Zhelobetskaia, E D

2012-01-01

The long-term effects of the ionizing radiation on the bioelectric brain activity in the Chernobyl nuclear disaster liquidators with discirculatory encephalopathy and arterial hypertension were studied. We examined 195 male patients, aged from 30 to 65 years, with the clinical presentations of discirculatory encephalopathy, using electroencephalography: 105 patients were liquidators of the Chernobyl nuclear disaster (the main group) and 90 patients had no radiation anamnesis (the comparison group). It has been found that the development of discirculatory encephalopathy in liquidators of the Chernobyl nuclear disaster is mainly associated with the dysfunction of diencephalic and cortical structures. The specificity of the neurofunctional brain abnormalities in liquidators with discirculatory encephalopathy is characterized by the predominance of the low-amplitude and low-frequency alpha-activity or by the lack of alpha-rhythm and by its substitution for the high-frequency beta-rhythm with the presence of theta- and delta-activity and by the more significant flatness of the alpha-rhythm zonation. The presence of the radiation factor in the past history is correlated with the failure of the bioelectric brain activity in the alpha band (r=0.42) that increases risk of abnormal changes by a factor of 10 (p<0.001). The liquidators with arterial hypertension are characterized by the more frequent occurrence of the asymmetry of the recorded bioelectric potentials between the similar hemispheric areas, by the more significant difference in the external stimulus response of the brain (functional tests). The results indicate the more complicated and diffuse lesion of the brain in the liquidators of the Chernobyl nuclear disaster in the post-radiation period during the development of discirculatory encephalopathy and arterial hypertension.

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.

Nuclear Society of Russia: Ten years in the world nuclear community

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

Ponomarev-Stepnoi, N.N.; Gagarinski, A.Yu.

2000-07-01

A nuclear society, which is a nongovernmental organization of nuclear professionals, appeared in the Soviet Union at the end of the 1980s--when social conditions for such a society had matured. Deep changes in the entire country's social consciousness had promoted the specialists understanding of the need to unite in order to overcome the nuclear community's dissociation, the monopoly of the nuclear ministry, and the secrecy syndrome of all nuclear issues. The new public association announced the guiding principles of its activities to be openness and glasnost and completeness and truthfulness of information supplied to decision makers and to the societymore » as a whole. Important to the information system of the NSR are topical meetings and seminars on quite varied but always actual problems of nuclear energy use, often with foreign participation. The variety of these NSR meeting subjects is illustrated by the titles of several meetings of the last 2 yr: Safety Culture in Nuclear Power, Youth and the Plutonium Challenge, Nuclear Fuel for Mankind, Nuclear Power in Space, Radiation Legacy of the Former-USSR, the Murmansk International Forum Nuclear Fleet and Ecology, and many others. A special place among NSR seminars belongs to the annual meeting, Nuclear Energy and Public Opinion, the Russian analog of the European PIME conference. Starting from distribution of ENS periodicals--the Nuclear Europe Worldscan magazine and Nucleus information sheet--among its members, the NSR soon began publishing its own Informational Bulletin (since 1989). Note that in the first years of the Nuclear Society's existence, it has been possible to publish periodicals, conference proceedings, and even books in English. Unfortunately, financial difficulties of the last years have frozen this most useful activity, which the NSR, however, hopes to resume. In the last period, the materials of the international information agency NucNet, which provides both regular information for the

The nuclear present. A guide to recent books on nuclear war, weapons, the peace movement, and related issues, with a chronology of nuclear events, 1789-1991

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

Burns, G.

The Nuclear Present brings the interested reader up-to-date on significant English-language books about nuclear weapons and related topics, identifying primarily important works of nuclear non-fiction that have come out since 1984. Each reference has a paragraph of comment about its subject and value. General organizational areas include the following: Reference Works; Nuclear weapons and Nuclear war (14 sub-headings including overviews, development, effects, tests, arms race, prospectives, legal considerations etc.); Strategy; proliferation; Stratigic Defense; Arms control and disarmament; ethical, pholosophical and religous perspectives; new paths to peace; periodic guide; the Chernobyl Disaster. An extensive Nuclear Chronology (1789-1991) written by the authormore » allows a fairly detailed sense of the historical record of nuclear weapons, including testing, manufacture, use and movements for arms control and disarmament.« less

Report Card on Nuclear Power

ERIC Educational Resources Information Center

Novick, Sheldon

1974-01-01

Problems facing the nuclear power industry include skyrocketing construction costs, technical failures, fuel scarcity, power plant safety, and the disposal of nuclear wastes. Possible solutions include: reductions in nuclear power plant construction, a complete moratorium on new plant construction, the construction of fast breeder reactors and the…

Nuclear Security for Floating Nuclear Power Plants

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

Skiba, James M.; Scherer, Carolynn P.

2015-10-13

Recently there has been a lot of interest in small modular reactors. A specific type of these small modular reactors (SMR,) are marine based power plants called floating nuclear power plants (FNPP). These FNPPs are typically built by countries with extensive knowledge of nuclear energy, such as Russia, France, China and the US. These FNPPs are built in one country and then sent to countries in need of power and/or seawater desalination. Fifteen countries have expressed interest in acquiring such power stations. Some designs for such power stations are briefly summarized. Several different avenues for cooperation in FNPP technology aremore » proposed, including IAEA nuclear security (i.e. safeguards), multilateral or bilateral agreements, and working with Russian design that incorporates nuclear safeguards for IAEA inspections in non-nuclear weapons states« less

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

Idaho Nuclear Technology and Engineering Center Low-Activity Waste Process Technology Program, FY-98 Status Report

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

Herbst, A.K.; Rogers, A.Z.; McCray, J.A.

The Low-Activity Waste Process Technology Program at the Idaho Nuclear Technology and Engineering Center (INTEC) anticipates that large volumes of low-level/low-activity wastes will need to be grouted prior to near-surface disposal. During fiscal year 1998, three grout formulations were studied for low-activity wastes derived from INTEC liquid sodium-bearing waste. Compressive strength and leach results are presented for phosphate bonding cement, acidic grout, and alkaline grout formulations. In an additional study, grout formulations are recommended for stabilization of the INTEC underground storage tank residual heels.

Development of Scintillators in Nuclear Medicine.

PubMed

Khoshakhlagh, Mohammad; Islamian, Jalil Pirayesh; Abedi, Seyed Mohammad; Mahmoudian, Babak

2015-01-01

High-quality image is necessary for accurate diagnosis in nuclear medicine. There are many factors in creating a good image and detector is the most important one. In recent years, several detectors are studied to get a better picture. The aim of this paper is comparison of some type of these detectors such as thallium activated sodium iodide bismuth germinate cesium activated yttrium aluminum garnet (YAG: Ce) YAP: Ce "lutetium aluminum garnet activated by cerium" CRY018 "CRY019" lanthanum bromide and cadmium zinc telluride. We studied different properties of these crystals including density, energy resolution and decay times that are more important factors affecting the image quality.

Support of the Iraq nuclear facility dismantlement and disposal program

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

Coates, Roger; Cochran, John; Danneels, Jeff

2007-07-01

Available in abstract form only. Full text of publication follows: Iraq's former nuclear facilities contain large quantities of radioactive materials and radioactive waste. The Iraq Nuclear Facility Dismantlement and Disposal Program (the Iraq NDs Program) is a new program to decontaminate and permanently dispose of radioactive wastes in Iraq. The NDs Program is led by the Government of Iraq, under International Atomic Energy Agency (IAEA) auspices, with guidance and assistance from a number of countries. The U.S. participants include Texas Tech University and Sandia National Laboratories. A number of activities are ongoing under the broad umbrella of the Iraq NDsmore » Program: drafting a new nuclear law that will provide the legal basis for the cleanup and disposal activities; assembly and analysis of existing data; characterization of soil contamination; bringing Iraqi scientists to the world's largest symposium on radioactive waste management; touring U.S. government and private sector operating radwaste disposal facilities in the U.S., and hosting a planning workshop on the characterization and cleanup of the Al-Tuwaitha Nuclear Facility. (authors)« 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

Spent Nuclear Fuel

EIA Publications

2015-01-01

Spent nuclear fuel data are collected by the U.S. Energy Information Administration (EIA) for the Department of Energy's Office of Standard Contract Management (Office of the General Counsel) on the Form GC-859, "Nuclear Fuel Data Survey." The data include detailed characteristics of spent nuclear fuel discharged from commercial U.S. nuclear power plants and currently stored at commercial sites in the United States. Utilities were not required to report spent nuclear fuel assemblies shipped to away-from-reactor, off-site facilities.

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

Nuclear glycogen and glycogen synthase kinase 3.

PubMed

Ragano-Caracciolo, M; Berlin, W K; Miller, M W; Hanover, J A

1998-08-19

Glycogen is the principal storage form of glucose in animal cells. It accumulates in electron-dense cytoplasmic granules and is synthesized by glycogen synthase (GS), the rate-limiting enzyme of glycogen deposition. Glycogen synthase kinase-3 (GSK-3) is a protein kinase that phosphorylates GS. Two nearly identical forms of GSK-3 exist: GSK-3 alpha and GSK-3 beta. Both are constitutively active in resting cells and their activity can be modulated by hormones and growth factors. GSK-3 is implicated in the regulation of many physiological responses in mammalian cells by phosphorylating substrates including neuronal cell adhesion molecule, neurofilaments, synapsin I, and tau. Recent observations point to functions for glycogen and glycogen metabolism in the nucleus. GSK-3 phosphorylates several transcription factors, and we have recently shown that it modifies the major nuclear pore protein p62. It also regulates PK1, a protein kinase required for maintaining the interphase state and for DNA replication in cycling Xenopus egg extracts. Recently, glycogen was shown to be required for nuclear reformation in vitro using ovulated Xenopus laevis egg lysates. Because neither glycogen nor GSK-3 has been localized to the nuclear envelope or intranuclear sites, glycogen and GSK-3 activites were measured in rat liver nuclei and nuclear reformation extracts. Significant quantities of glycogen-like material co-purified with the rat-liver nuclear envelope. GSK-3 is also highly enriched in the glycogen pellet of egg extracts of Xenopus that is required for nuclear assembly in vitro. Based on the finding that enzymes of glycogen metabolism copurify with glycogen, we propose that glycogen may serve a structural role as a scaffold for nuclear assembly and sequestration of critical kinases and phosphatases in the nucleus. Copyright 1998 Academic Press.

Role of Bioavailable Iron in Coal Dust-Induced Activation of Activator Protein-1 and Nuclear Factor of Activated T Cells

PubMed Central

Huang, Chuanshu; Li, Jingxia; Zhang, Qi; Huang, Xi

2010-01-01

Activator protein-1 (AP-1) and nuclear factor of activated T cells (NFAT) are two important transcription factors responsible for the regulation of cytokines, which are involved in cell proliferation and inflammation. Coal workers’ pneumoconiosis (CWP) is an occupational lung disease that may be related to chronic inflammation caused by coal dust exposure. In the present study, we demonstrate that coal from the Pennsylvania (PA) coalmine region, which has a high prevalence of CWP, can activate both AP-1 and NFAT in JB6 mouse epidermal cells. In contrast, coal from the Utah (UT) coalmine region, which has a low prevalence of CWP, has no such effects. The PA coal stimulates mitogen-activated protein kinase (MAPK) family members of extracellular signal-regulated kinases (ERKs) and p38 MAPK but not c-Jun-NH2-terminal kinases, as determined by the phosphorylation assay. The increase in AP-1 by the PA coal was completely eliminated by the pretreatment of cells with PD98059, a specific MAPK kinase inhibitor, and SB202190, a p38 kinase inhibitor, further confirming that the PA coal-induced AP-1 activation is mediated through ERKs and p38 MAPK pathways. Deferoxamine (DFO), an iron chelator, synergistically enhanced the PA coal-induced AP-1 activity, but inhibited NFAT activity. For comparison, cells were treated with ferrous sulfate and/or DFO. We have found that iron transactivated both AP-1 and NFAT, and DFO further enhanced iron-induced AP-1 activation but inhibited NFAT. These results indicate that activation of AP-1 and NFAT by the PA coal is through bioavailable iron present in the coal. These data are in agreement with our previous findings that the prevalence of CWP correlates well with levels of bioavailable iron in coals from various mining regions. PMID:12397016

Spontaneous 15N Nuclear Spin Hyperpolarization in Metal-Free Activation of Parahydrogen by Molecular Tweezers

PubMed Central

2018-01-01

The ability of frustrated Lewis pairs (FLPs) to activate H2 is of significant interest for metal-free catalysis. The activation of H2 is also the key element of parahydrogen-induced polarization (PHIP), one of the nuclear spin hyperpolarization techniques. It is demonstrated that o-phenylene-based ansa-aminoboranes (AABs) can produce 1H nuclear spin hyperpolarization through a reversible interaction with parahydrogen at ambient temperatures. Heteronuclei are useful in NMR and MRI as well because they have a broad chemical shift range and long relaxation times and may act as background-free labels. We report spontaneous formation of 15N hyperpolarization of the N–H site for a family of AABs. The process is efficient at the high magnetic field of an NMR magnet (7 T), and it provides up to 350-fold 15N signal enhancements. Different hyperpolarization effects are observed with various AAB structures and in a broad temperature range. Spontaneous hyperpolarization, albeit an order of magnitude weaker than that for 15N, was also observed for 11B nuclei. PMID:29401399

25 CFR 170.623 - How are IRR Program projects and activities included in a self-governance agreement?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How are IRR Program projects and activities included in a self-governance agreement? 170.623 Section 170.623 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE... self-governance agreement? To include an IRR Program project or activity in a self-governance agreement...

Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors.

PubMed

Melis, Miriam; Pillolla, Giuliano; Luchicchi, Antonio; Muntoni, Anna Lisa; Yasar, Sevil; Goldberg, Steven R; Pistis, Marco

2008-12-17

Nicotine stimulates the activity of mesolimbic dopamine neurons, which is believed to mediate the rewarding and addictive properties of tobacco use. Accumulating evidence suggests that the endocannabinoid system might play a major role in neuronal mechanisms underlying the rewarding properties of drugs of abuse, including nicotine. Here, we investigated the modulation of nicotine effects by the endocannabinoid system on dopamine neurons in the ventral tegmental area with electrophysiological techniques in vivo and in vitro. We discovered that pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme that catabolizes fatty acid ethanolamides, among which the endocannabinoid anandamide (AEA) is the best known, suppressed nicotine-induced excitation of dopamine cells. Importantly, this effect was mimicked by the administration of the FAAH substrates oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), but not methanandamide, the hydrolysis resistant analog of AEA. OEA and PEA are naturally occurring lipid signaling molecules structurally related to AEA, but devoid of affinity for cannabinoid receptors. They blocked the effects of nicotine by activation of the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), a nuclear receptor transcription factor involved in several aspects of lipid metabolism and energy balance. Activation of PPAR-alpha triggered a nongenomic stimulation of tyrosine kinases, which might lead to phosphorylation and negative regulation of neuronal nicotinic acetylcholine receptors. These data indicate for the first time that the anorexic lipids OEA and PEA possess neuromodulatory properties as endogenous ligands of PPAR-alpha in the brain and provide a potential new target for the treatment of nicotine addiction.

Regulation of Stress-Inducible Phosphoprotein 1 Nuclear Retention by Protein Inhibitor of Activated STAT PIAS1

PubMed Central

Soares, Iaci N.; Caetano, Fabiana A.; Pinder, Jordan; Rodrigues, Bruna Roz; Beraldo, Flavio H.; Ostapchenko, Valeriy G.; Durette, Chantal; Pereira, Grace Schenatto; Lopes, Marilene H.; Queiroz-Hazarbassanov, Nicolle; Cunha, Isabela W.; Sanematsu, Paulo I.; Suzuki, Sergio; Bleggi-Torres, Luiz F.; Schild-Poulter, Caroline; Thibault, Pierre; Dellaire, Graham; Martins, Vilma R.; Prado, Vania F.; Prado, Marco A. M.

2013-01-01

Stress-inducible phosphoprotein 1 (STI1), a cochaperone for Hsp90, has been shown to regulate multiple pathways in astrocytes, but its contributions to cellular stress responses are not fully understood. We show that in response to irradiation-mediated DNA damage stress STI1 accumulates in the nucleus of astrocytes. Also, STI1 haploinsufficiency decreases astrocyte survival after irradiation. Using yeast two-hybrid screenings we identified several nuclear proteins as STI1 interactors. Overexpression of one of these interactors, PIAS1, seems to be specifically involved in STI1 nuclear retention and in directing STI1 and Hsp90 to specific sub-nuclear regions. PIAS1 and STI1 co-immunoprecipitate and PIAS1 can function as an E3 SUMO ligase for STI. Using mass spectrometry we identified five SUMOylation sites in STI1. A STI1 mutant lacking these five sites is not SUMOylated, but still accumulates in the nucleus in response to increased expression of PIAS1, suggesting the possibility that a direct interaction with PIAS1 could be responsible for STI1 nuclear retention. To test this possibility, we mapped the interaction sites between PIAS1 and STI1 using yeast-two hybrid assays and surface plasmon resonance and found that a large domain in the N-terminal region of STI1 interacts with high affinity with amino acids 450–480 of PIAS1. Knockdown of PIAS1 in astrocytes impairs the accumulation of nuclear STI1 in response to irradiation. Moreover, a PIAS1 mutant lacking the STI1 binding site is unable to increase STI1 nuclear retention. Interestingly, in human glioblastoma multiforme PIAS1 expression is increased and we found a significant correlation between increased PIAS1 expression and STI1 nuclear localization. These experiments provide evidence that direct interaction between STI1 and PIAS1 is involved in the accumulation of nuclear STI1. This retention mechanism could facilitate nuclear chaperone activity. PMID:23938469

Swelling-resistant nuclear fuel

DOEpatents

Arsenlis, Athanasios [Hayward, CA; Satcher, Jr., Joe; Kucheyev, Sergei O [Oakland, CA

2011-12-27

A nuclear fuel according to one embodiment includes an assembly of nuclear fuel particles; and continuous open channels defined between at least some of the nuclear fuel particles, wherein the channels are characterized as allowing fission gasses produced in an interior of the assembly to escape from the interior of the assembly to an exterior thereof without causing significant swelling of the assembly. Additional embodiments, including methods, are also presented.

Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow-derived macrophages.

PubMed

Kim, A-Ram; Kim, Hyuk Soon; Lee, Jeong Min; Choi, Jung Ho; Kim, Se Na; Kim, Do Kyun; Kim, Ji Hyung; Mun, Se Hwan; Kim, Jie Wan; Jeon, Hyun Soo; Kim, Young Mi; Choi, Wahn Soo

2012-05-05

Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Heterogeneous nuclear ribonucleoprotein K inhibits heat shock-induced transcriptional activity of heat shock factor 1.

PubMed

Kim, Hee-Jung; Lee, Jae-Jin; Cho, Jin-Hwan; Jeong, Jaeho; Park, A Young; Kang, Wonmo; Lee, Kong-Joo

2017-08-04

When cells are exposed to heat shock and various other stresses, heat shock factor 1 (HSF1) is activated, and the heat shock response (HSR) is elicited. To better understand the molecular regulation of the HSR, we used 2D-PAGE-based proteome analysis to screen for heat shock-induced post-translationally modified cellular proteins. Our analysis revealed that two protein spots typically present on 2D-PAGE gels and containing heterogeneous nuclear ribonucleoprotein K (hnRNP K) with trioxidized Cys 132 disappeared after the heat shock treatment and reappeared during recovery, but the total amount of hnRNP K protein remained unchanged. We next tested whether hnRNP K plays a role in HSR by regulating HSF1 and found that hnRNP K inhibits HSF1 activity, resulting in reduced expression of hsp70 and hsp27 mRNAs. hnRNP K also reduced binding affinity of HSF1 to the heat shock element by directly interacting with HSF1 but did not affect HSF1 phosphorylation-dependent activation or nuclear localization. hnRNP K lost its ability to induce these effects when its Cys 132 was substituted with Ser, Asp, or Glu. These findings suggest that hnRNP K inhibits transcriptional activity of HSF1 by inhibiting its binding to heat shock element and that the oxidation status of Cys 132 in hnRNP K is critical for this inhibition. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Daphnia HR96 is a Promiscuous Xenobiotic and Endobiotic Nuclear Receptor

PubMed Central

Karimullina, Elina; Li, Yangchun; Ginjupalli, Gautam; Baldwin, William S.

2012-01-01

Daphnia pulex is the first crustacean to have its genome sequenced. The genome project provides new insight and data into how an aquatic crustacean may respond to environmental stressors, including toxicants. We cloned Daphnia pulex HR96 (DappuHR96), a nuclear receptor orthologous to the CAR/PXR/VDR group of nuclear receptors. In Drosophila melanogaster, (hormone receptor 96) HR96 responds to phenobarbital exposure and has been hypothesized as a toxicant receptor. Therefore, we set up a transactivation assay to test whether DappuHR96 is a promiscuous receptor activated by xenobiotics and endobiotics similar to the constitutive androstane receptor (CAR) and the pregnane X-receptor (PXR). Transactivation assays performed with a GAL4-HR96 chimera demonstrate that HR96 is a promiscuous toxicant receptor activated by a diverse set of chemicals such as pesticides, hormones, and fatty acids. Several environmental toxicants activate HR96 including estradiol, pyriproxyfen, chlorpyrifos, atrazine, and methane arsonate. We also observed repression of HR96 activity by chemicals such as triclosan, androstanol, and fluoxetine. Nearly 50% of the chemicals tested activated or inhibited HR96. Interestingly, unsaturated fatty acids were common activators or inhibitors of HR96 activity, indicating a link between diet and toxicant response. The omega-6 and omega-9 unsaturated fatty acids linoleic and oleic acid activated HR96, but the omega-3 unsaturated fatty acids alpha-linolenic acid and docosahexaenoic acid inhibited HR96, suggesting that these two distinct sets of lipids perform opposing roles in Daphnia physiology. This also provides a putative mechanism by which the ratio of dietary unsaturated fats may affect the ability of an organism to respond to a toxic insult. In summary, HR96 is a promiscuous nuclear receptor activated by numerous endo- and xenobiotics. PMID:22466357

Nuclear Forensic Science: Analysis of Nuclear Material Out of Regulatory Control

NASA Astrophysics Data System (ADS)

Kristo, Michael J.; Gaffney, Amy M.; Marks, Naomi; Knight, Kim; Cassata, William S.; Hutcheon, Ian D.

2016-06-01

Nuclear forensic science seeks to identify the origin of nuclear materials found outside regulatory control. It is increasingly recognized as an integral part of a robust nuclear security program. This review highlights areas of active, evolving research in nuclear forensics, with a focus on analytical techniques commonly employed in Earth and planetary sciences. Applications of nuclear forensics to uranium ore concentrates (UOCs) are discussed first. UOCs have become an attractive target for nuclear forensic researchers because of the richness in impurities compared to materials produced later in the fuel cycle. The development of chronometric methods for age dating nuclear materials is then discussed, with an emphasis on improvements in accuracy that have been gained from measurements of multiple radioisotopic systems. Finally, papers that report on casework are reviewed, to provide a window into current scientific practice.

FENDL: International reference nuclear data library for fusion applications

NASA Astrophysics Data System (ADS)

Pashchenko, A. B.; Wienke, H.; Ganesan, S.

1996-10-01

The IAEA Nuclear Data Section, in co-operation with several national nuclear data centres and research groups, has created the first version of an internationally available Fusion Evaluated Nuclear Data Library (FENDL-1). The FENDL library has been selected to serve as a comprehensive source of processed and tested nuclear data tailored to the requirements of the engineering design activity (EDA) of the ITER project and other fusion-related development projects. The present version of FENDL consists of the following sublibraries covering the necessary nuclear input for all physics and engineering aspects of the material development, design, operation and safety of the ITER project in its current EDA phase: FENDL/A-1.1: neutron activation cross-sections, selected from different available sources, for 636 nuclides, FENDL/D-1.0: nuclear decay data for 2900 nuclides in ENDF-6 format, FENDL/DS-1.0: neutron activation data for dosimetry by foil activation, FENDL/C-1.0: data for the fusion reactions D(d,n), D(d,p), T(d,n), T(t,2n), He-3(d,p) extracted from ENDF/B-6 and processed, FENDL/E-1.0:data for coupled neutron—photon transport calculations, including a data library for neutron interaction and photon production for 63 elements or isotopes, selected from ENDF/B-6, JENDL-3, or BROND-2, and a photon—atom interaction data library for 34 elements. The benchmark validation of FENDL-1 as required by the customer, i.e. the ITER team, is considered to be a task of high priority in the coming months. The well tested and validated nuclear data libraries in processed form of the FENDL-2 are expected to be ready by mid 1996 for use by the ITER team in the final phase of ITER EDA after extensive benchmarking and integral validation studies in the 1995-1996 period. The FENDL data files can be electronically transferred to users from the IAEA nuclear data section online system through INTERNET. A grand total of 54 (sub)directories with 845 files with total size of about 2

The oxidative stress mediator 4-hydroxynonenal is an intracellular agonist of the nuclear receptor peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)

PubMed Central

Coleman, Jeffrey D.; Prabhu, K. Sandeep; Thompson, Jerry T.; Reddy, P. Sreenivasula; Peters, Jeffrey M.; Peterson, Blake R.; Reddy, C. Channa; Vanden Heuvel, John P.

2007-01-01

Liver insufficiency and damage is a major cause of death and disease worldwide and may result from exposure to environmental toxicants, specific combinations or dosages of pharmaceuticals and microbial metabolites. The generation of reactive intermediates, in particular 4-hydroxynonenal (4-HNE), is a common event in liver damage caused by a variety of hepatotoxic drugs and solvents. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are involved in the transcriptional regulation of lipid metabolism as well as other biological functions. Importantly, we have observed that the PPARβ/δ−/− mouse is more susceptible to chemically-induced hepatotoxicity than its wildtype counterpart, and our objective in this study was to elucidate the mechanism(s) by which PPARβ/δ confers protection to hepatocytes. We hypothesized that PPARβ/δ plays a protective role by responding to toxic lipids and altering gene expression accordingly. In support, oxidized-VLDL and constituents including 13-S-hydroxyoctadeca-dienoic acid (13(S)-HODE) and 4-HNE are PPARβ/δ ligands. A structure-activity relationship was established where 4-HNE and 4-hydroperoxynonenal (4-HpNE) enhanced the activity of the PPARβ/δ subtype while 4-hyroxy-hexenal (4-HHE), 4-oxo-2-Nonenal (4-ONE), and trans-4,5-epoxy-2(E)-decenal did not activate this receptor. Increasing PPARβ/δ activity with a synthetic agonist decreased sensitivity of hepatocytes to 4-HNE and other toxic agents, whereas inhibition of this receptor had the opposite result. Gene expression microarray analysis identified several important PPARβ/δ-regulated detoxification enzymes involved in 4-HNE metabolism that are regulated at the transcript level. This research established 4-HNE as an endogenous modulator of PPARβ/δ activity and raises the possibility that agonists of this nuclear receptor may be utilized to prevent or treat liver disease associated with oxidative damage. PMID:17382197

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation.

PubMed

Moussaieff, Arieh; Shohami, Esther; Kashman, Yoel; Fride, Ester; Schmitz, M Lienhard; Renner, Florian; Fiebich, Bernd L; Munoz, Eduardo; Ben-Neriah, Yinon; Mechoulam, Raphael

2007-12-01

Boswellia resin is a major anti-inflammatory agent in herbal medical tradition, as well as a common food supplement. Its anti-inflammatory activity has been attributed to boswellic acid and its derivatives. Here, we re-examined the anti-inflammatory effect of the resin, using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells for a bioassay-guided fractionation. We thus isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole (IN). IA inhibited TAK/TAB-mediated IkappaB kinase (IKK) activation loop phosphorylation, resulting in the inhibition of cytokine and lipopolysaccharide-mediated NF-kappaB activation. It had no effect on IKK activity in vitro, and it did not suppress IkappaB alpha phosphorylation in costimulated T-cells, indicating that the kinase inhibition is neither direct nor does it affect all NF-kappaB activation pathways. The inhibitory effect seems specific; IA did not interfere with TNFalpha-induced activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase. IA treatment had a robust anti-inflammatory effect in a mouse inflamed paw model. Cembrenoid diterpenoids, specifically IA and its derivatives, may thus constitute a potential novel group of NF-kappaB inhibitors, originating from an ancient anti-inflammatory herbal remedy.

Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

PubMed

Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

2018-01-01

Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights 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...

Fatty Acid Amide Hydrolase (FAAH) Inhibition Enhances Memory Acquisition through Activation of PPAR-alpha Nuclear Receptors

ERIC Educational Resources Information Center

Mazzola, Carmen; Medalie, Julie; Scherma, Maria; Panlilio, Leigh V.; Solinas, Marcello; Tanda, Gianluigi; Drago, Filippo; Cadet, Jean Lud; Goldberg, Steven R.; Yasar, Sevil

2009-01-01

Inhibitors of fatty acid amide hydrolase (FAAH) increase endogenous levels of anandamide (a cannabinoid CB[subscript 1]-receptor ligand) and oleoylethanolamide and palmitoylethanolamide (OEA and PEA, ligands for alpha-type peroxisome proliferator-activated nuclear receptors, PPAR-alpha) when and where they are naturally released in the brain.…

Ex Vivo Activity of Endoperoxide Antimalarials, Including Artemisone and Arterolane, against Multidrug-Resistant Plasmodium falciparum Isolates from Cambodia

DTIC Science & Technology

2014-10-01

OCT 2014 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Ex Vivo Activity of Endoperoxide Antimalarials , Including Artemisone...Prescribed by ANSI Std Z39-18 Ex Vivo Activity of Endoperoxide Antimalarials , Including Artemisone and Arterolane, against Multidrug-Resistant...potent antimalarial activity (2, 3). Despite having a rapid mecha- nism of action, artemisinin resistance eventually emerged and was first detected

Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway

PubMed Central

Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A.; Johnson, Jeffrey A.

2013-01-01

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in-vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H2O2 induced cell death. PMID:23507152

International nuclear fuel cycle fact book. Revision 4

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

Harmon, K.M.; Lakey, L.T.; Leigh, I.W.

This Fact Book has been compiled in an effort to provide (1) an overview of worldwide nuclear power and fuel cycle programs and (2) current data concerning fuel cycle and waste management facilities, R and D programs, and key personnel in countries other than the United States. Additional information on each country's program is available in the International Source Book: Nuclear Fuel Cycle Research and Development, PNL-2478, Rev. 2. The Fact Book is organized as follows: (1) Overview section - summary tables which indicate national involvement in nuclear reactor, fuel cycle, and waste management development activities; (2) national summaries -more » a section for each country which summarizes nuclear policy, describes organizational relationships and provides addresses, names of key personnel, and facilities information; (3) international agencies - a section for each of the international agencies which has significant fuel cycle involvement; (4) energy supply and demand - summary tables, including nuclear power projections; (5) fuel cycle - summary tables; and (6) travel aids - international dialing instructions, international standard time chart, passport and visa requirements, and currency exchange rate.« less

International Nuclear Fuel Cycle Fact Book. Revision 5

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

Harmon, K.M.; Lakey, L.T.; Leigh, I.W.

This Fact Book has been compiled in an effort to provide: (1) an overview of worldwide nuclear power and fuel cycle programs; and (2) current data concerning fuel cycle and waste management facilities, R and D programs, and key personnel in countries other than the United States. Additional information on each country's program is available in the International Source Book: Nuclear Fuel Cycle Research and Development, PNL-2478, Rev. 2. The Fact Book is organized as follows: (1) Overview section - summary tables which indicate national involvement in nuclear reactor, fuel cycle, and waste management development activities; (2) national summaries -more » a section for each country which summarizes nuclear policy, describes organizational relationships and provides addresses, names of key personnel, and facilities information; (3) international agencies - a section for each of the international agencies which has significant fuel cycle involvement; (4) energy supply and demand - summary tables, including nuclear power projections; (5) fuel cycle - summary tables; and (6) travel aids international dialing instructions, international standard time chart, passport and visa requirements, and currency exchange rate.« less

Including students with moderate and severe intellectual disabilities in school extracurricular and community recreation activities.

PubMed

Kleinert, Harold L; Miracle, Sally; Sheppard-Jones, Kathy

2007-02-01

We conducted an online statewide survey of teachers of students with moderate and severe intellectual disabilities to determine the extent to which their students were included in school extracurricular and community recreation activities. For the 252 teacher respondents who indicated that their primary caseload consisted of students with significant intellectual disabilities, we report the numbers of students participating in school and community activities and the primary type of support students required to participate in each activity. Finally, we identify implications for practitioners who want to increase the participation of students with significant disabilities in school and community activities.

Nuclear option

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

Olson, P.S.

The energy demand complexion of this country is always changing and promises to change in the future. The nuclear industry is responding to changing energy demands through standards writing activities. Since the oil embargo of 1973, there has been a change in the mix of fuels contributing to energy growth in this country; virtually all of the energy growth has come from coal and nuclear power. The predicted expansion of coal use by 1985, over 1977 level, is 37%, while the use of oil is expected to decline by 17%. Use of nuclear power is expected to increase 62% frommore » the 1977 level. The feasibility of using nuclear energy to meet the needs of the USA for electric power is discussed.« less

Targeting nuclear receptors for the treatment of fatty liver disease.

PubMed

Tanaka, Naoki; Aoyama, Toshifumi; Kimura, Shioko; Gonzalez, Frank J

2017-11-01

Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis. Recently, disorders associated with disrupted nutrient/energy homeostasis, e.g., obesity, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD), are increasing worldwide. Notably, in NAFLD, a progressive subtype exists, designated as non-alcoholic steatohepatitis (NASH) that is characterized by typical histological features resembling alcoholic steatohepatitis (ASH), and NASH/ASH are recognized as major causes of hepatitis virus-unrelated liver cirrhosis and hepatocellular carcinoma. Since hepatic steatosis is basically caused by an imbalance between fat/energy influx and utilization, abnormal signaling of these nuclear receptors contribute to the pathogenesis of fatty liver disease. Standard therapeutic interventions have not been fully established for fatty liver disease, but some new agents that activate or inhibit nuclear receptor signaling have shown promise as possible therapeutic targets. In this review, we summarize recent findings on the roles of nuclear receptors in fatty liver disease and discuss future perspectives to develop promising pharmacological strategies targeting nuclear receptors for NAFLD/NASH. Copyright © 2017 Elsevier Inc. All rights reserved.

VI European Summer School on Experimental Nuclear Astrophysics

NASA Astrophysics Data System (ADS)

The European Summer School on Experimental Nuclear Astrophysics has reached the sixth edition, marking the tenth year's anniversary. The spirit of the school is to provide a very important occasion for a deep education of young researchers about the main topics of experimental nuclear astrophysics. Moreover, it should be regarded as a forum for the discussion of the last-decade research activity. Lectures are focused on various aspects of primordial and stellar nucleosynthesis, including novel experimental approaches and detectors, indirect methods and radioactive ion beams. Moreover, in order to give a wide educational offer, some lectures cover complementary subjects of nuclear astrophysics such as gamma ray astronomy, neutron-induced reactions, short-lived radionuclides, weak interaction and cutting-edge facilities used to investigate nuclear reactions of interest for astrophysics. Large room is also given to young researcher oral contributions. Traditionally, particular attention is devoted to the participation of students from less-favoured countries, especially from the southern coast of the Mediterranean Sea. The school is organised by the Catania Nuclear Astrophysics research group with the collaboration of Dipartimento di Fisica e Astromomia - Università di Catania and Laboratori Nazionali del Sud - Istituto Nazionale di Fisica Nucleare.

Cost effective nuclear commercial grade dedication

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

Maletz, J.J.; Marston, M.J.

1991-01-01

This paper describes a new computerized database method to create/edit/view specification technical data sheets (mini-specifications) for procurement of spare parts for nuclear facility maintenance and to develop information that could support possible future facility life extension efforts. This method may reduce cost when compared with current manual methods. The use of standardized technical data sheets (mini-specifications) for items of the same category improves efficiency. This method can be used for a variety of tasks, including: Nuclear safety-related procurement; Non-safety related procurement; Commercial grade item procurement/dedication; Evaluation of replacement items. This program will assist the nuclear facility in upgrading its procurementmore » activities consistent with the recent NUMARC Procurement Initiative. Proper utilization of the program will assist the user in assuring that the procured items are correct for the applications, provide data to assist in detecting fraudulent materials, minimize human error in withdrawing database information, improve data retrievability, improve traceability, and reduce long-term procurement costs.« less

The anti-allergic activity of Cymbopogon citratus is mediated via inhibition of nuclear factor kappa B (Nf-Κb) activation.

PubMed

Santos Serafim Machado, Marta; Ferreira Silva, Hugo Bernardino; Rios, Raimon; Pires de Oliveira, Anaque; Vilany Queiroz Carneiro, Noma; Santos Costa, Ryan; Santos Alves, William; Meneses Souza, Fabio-Luis; da Silva Velozo, Eudes; Alves de Souza, Silvana; Sarmento Silva, Tania Maria; Silva, Maria Lenise; Pontes-de-Carvalho, Lain Carlos; Alcântara-Neves, Neuza Maria; Figueiredo, Camila Alexandrina

2015-06-06

The prevalence of allergic diseases such as asthma has significantly increased worldwide, making it a public health concern. There is an urgent need for new anti-inflammatory agents with selective pharmacology and lower toxicity. Plant extracts have been used for centuries in traditional medicine to alleviate inflammatory diseases. In this work, we evaluated the anti-allergic activity of Cymbopogon citratus (Cy), a medicinal herb used by folk medicine to treat asthma. We used a murine model of respiratory allergy to the mite Blomia tropicalis (Bt) and evaluated certain parameters known to be altered in this model. A/J mice were sensitized (100 μg/animal s.c.) and challenged (10 μg/animal i.n.) with Bt mite extract and treated with 60, 120 or 180 mg/kg of Cy standardized hexane extract. The parameters evaluated included: cellular infiltrate in bronchoalveolar lavage (BAL); eosinophil peroxidase activity (EPO); histopathological examination of the lung; serum levels of specific IgE, IgG1 and IgG2a; Th2 cytokine concentrations in BAL and expression of NF-κB. Our results showed that oral administration of a Cy hexane extract (especially 180 mg/Kg) reduced the numbers of leukocytes/eosinophils in BAL; the eosinophil peroxidase activity in BAL; the infiltration of leukocytes in lung tissue; the production of mucus in the respiratory tract; the level of IL-4 in BAL and the nuclear expression of NF-κB. The results presented demonstrate the potential of the Cy hexane extract to modulate allergic asthma; this extract may be an alternative future approach to treat this pathology.

Thioredoxin-mediated denitrosylation regulates cytokine-induced nuclear factor κB (NF-κB) activation.

PubMed

Kelleher, Zachary T; Sha, Yonggang; Foster, Matthew W; Foster, W Michael; Forrester, Michael T; Marshall, Harvey E

2014-01-31

S-nitrosylation of nuclear factor κB (NF-κB) on the p65 subunit of the p50/p65 heterodimer inhibits NF-κB DNA binding activity. We have recently shown that p65 is constitutively S-nitrosylated in the lung and that LPS-induced injury elicits a decrease in SNO-p65 levels concomitant with NF-κB activation in the respiratory epithelium and initiation of the inflammatory response. Here, we demonstrate that TNFα-mediated activation of NF-κB in the respiratory epithelium similarly induces p65 denitrosylation. This process is mediated by the denitrosylase thioredoxin (Trx), which becomes activated upon cytokine-induced degradation of thioredoxin-interacting protein (Txnip). Similarly, inhibition of Trx activity in the lung attenuates LPS-induced SNO-p65 denitrosylation, NF-κB activation, and airway inflammation, supporting a pathophysiological role for this mechanism in lung injury. These data thus link stimulus-coupled activation of NF-κB to a specific, protein-targeted denitrosylation mechanism and further highlight the importance of S-nitrosylation in the regulation of the immune response.

Nuclear Photonics

NASA Astrophysics Data System (ADS)

Nedorezov, V. G.; Savel'ev-Trofimov, A. B.

2017-12-01

A review of works performed at the Institute for Nuclear Research of the Russian Academy of Sciences and at the International Laser Center of the Moscow State University in the context of the new research area called "nuclear photonics" is presented. Nuclear photonics is based on creation of the new-generation gamma-ray sources which make it possible to solve a number of fundamental and applied problems, including research of low-energy photonuclear reactions, namely, investigation of collective excitations of nuclei near the threshold (pygmy resonances); nuclear safety assurance; production of low-energy positron beams; and phase-contrast X-ray imaging.

The Epstein–Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression

PubMed Central

Ruvolo, Vivian; Wang, Eryu; Boyle, Sarah; Swaminathan, Sankar

1998-01-01

The Epstein–Barr virus (EBV) nuclear protein BS-MLF1 (SM) is expressed early after entry of EBV into the lytic cycle. SM transactivates reporter gene constructs driven by a wide variety of promoters, but the mechanism of SM action is poorly understood. In this study, we demonstrate that the SM protein inhibits expression of intron-containing genes and activates expression of intron-less genes. We demonstrate that SM has the predicted inhibitory effect on expression of a spliced EBV gene but activates an unspliced early EBV gene. SM inhibited gene expression at the post-transcriptional level by preventing the accumulation of nuclear and cytoplasmic RNA transcripts. Conversely, SM led to increased accumulation of nuclear mRNA from intron-less genes without affecting the rate of transcription, indicating that SM enhances nuclear RNA stability. The ratio of cytoplasmic to nuclear polyadenylated mRNA was increased in the presence of SM, suggesting that SM also enhances nucleo-cytoplasmic mRNA transport. The degree of transactivation by SM was dependent on the sequence of the 3′-untranslated region of the target mRNA. Finally, we demonstrate that the amino-terminal portion of SM fused to glutathione-S-transferase binds radioactively labeled RNA in vitro, indicating that SM is a single-stranded RNA binding protein. Importantly, the latent and immediate-early genes of EBV contain introns whereas many early and late genes do not. Thus, SM may down-regulate synthesis of host cell proteins and latent EBV proteins while simultaneously enhancing expression of specific lytic EBV genes by binding to mRNA and modulating its stability and transport. PMID:9671768

The Epstein-Barr virus nuclear protein SM is both a post-transcriptional inhibitor and activator of gene expression.

PubMed

Ruvolo, V; Wang, E; Boyle, S; Swaminathan, S

1998-07-21

The Epstein-Barr virus (EBV) nuclear protein BS-MLF1 (SM) is expressed early after entry of EBV into the lytic cycle. SM transactivates reporter gene constructs driven by a wide variety of promoters, but the mechanism of SM action is poorly understood. In this study, we demonstrate that the SM protein inhibits expression of intron-containing genes and activates expression of intron-less genes. We demonstrate that SM has the predicted inhibitory effect on expression of a spliced EBV gene but activates an unspliced early EBV gene. SM inhibited gene expression at the post-transcriptional level by preventing the accumulation of nuclear and cytoplasmic RNA transcripts. Conversely, SM led to increased accumulation of nuclear mRNA from intron-less genes without affecting the rate of transcription, indicating that SM enhances nuclear RNA stability. The ratio of cytoplasmic to nuclear polyadenylated mRNA was increased in the presence of SM, suggesting that SM also enhances nucleo-cytoplasmic mRNA transport. The degree of transactivation by SM was dependent on the sequence of the 3'-untranslated region of the target mRNA. Finally, we demonstrate that the amino-terminal portion of SM fused to glutathione-S-transferase binds radioactively labeled RNA in vitro, indicating that SM is a single-stranded RNA binding protein. Importantly, the latent and immediate-early genes of EBV contain introns whereas many early and late genes do not. Thus, SM may down-regulate synthesis of host cell proteins and latent EBV proteins while simultaneously enhancing expression of specific lytic EBV genes by binding to mRNA and modulating its stability and transport.

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.

The human papillomavirus (HPV) E6 oncoproteins promotes nuclear localization of active caspase 8

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

Manzo-Merino, Joaquin; Massimi, Paola; Lizano, Marcela, E-mail: lizanosoberon@gmail.com

The HPV-16 E6 and E6{sup ⁎} proteins have been shown previously to be capable of regulating caspase 8 activity. We now show that the capacity of E6 to interact with caspase 8 is common to diverse HPV types, being also seen with HPV-11 E6, HPV-18 E6 and HPV-18 E6{sup ⁎}. Unlike most E6-interacting partners, caspase 8 does not appear to be a major proteasomal target of E6, but instead E6 appears able to stimulate caspase 8 activation, without affecting the overall apoptotic activity. This would appear to be mediated in part by the ability of the HPV E6 oncoproteins tomore » recruit active caspase 8 to the nucleus. - Highlights: • Multiple HPV E6 oncoproteins interact with the caspase 8 DED domain. • HPV E6 stimulates activation of caspase 8. • HPV E6 promotes nuclear accumulation of caspase 8.« less

Partially ionized plasmas including the third symposium on uranium plasmas

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

Krishnan, M.

1976-09-01

Separate abstracts are included for 28 papers on electrically generated plasmas, fission generated plasmas, nuclear pumped lasers, gaseous fuel reactor research, and applications. Five papers have been previously abstracted and included in ERA.

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

PubMed

Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

2016-03-01

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

Insight into the functional organization of nuclear lamins in health and disease.

PubMed

Tatli, Meltem; Medalia, Ohad

2018-05-22

Lamins are the main component of the nuclear lamina, a protein meshwork at the inner nuclear membrane which primarily provide mechanical stability to the nucleus. Lamins, type V intermediate filament proteins, are also involved in many nuclear activities. Structural analysis of nuclei revealed that lamins form 3.5nm thick filaments often interact with nuclear pore complexes. Mutations in the LMNA gene, encoding A-type lamins, have been associated with at least 15 distinct diseases collectively termed laminopathies, including muscle, metabolic and neurological disorders, and premature aging syndrome. It is unclear how laminopathic mutations lead to such a wide array of diseases, essentially affecting almost all tissues. Copyright © 2018 Elsevier Ltd. All rights reserved.

Phytol metabolites are circulating dietary factors that activate the nuclear receptor RXR.

PubMed Central

Kitareewan, S; Burka, L T; Tomer, K B; Parker, C E; Deterding, L J; Stevens, R D; Forman, B M; Mais, D E; Heyman, R A; McMorris, T; Weinberger, C

1996-01-01

RXR is a nuclear receptor that plays a central role in cell signaling by pairing with a host of other receptors. Previously, 9-cis-retinoic acid (9cRA) was defined as a potent RXR activator. Here we describe a unique RXR effector identified from organic extracts of bovine serum by following RXR-dependent transcriptional activity. Structural analyses of material in active fractions pointed to the saturated diterpenoid phytanic acid, which induced RXR-dependent transcription at concentrations between 4 and 64 microM. Although 200 times more potent than phytanic acid, 9cRA was undetectable in equivalent amounts of extract and cannot be present at a concentration that could account for the activity. Phytanic acid, another phytol metabolite, was synthesized and stimulated RXR with a potency and efficacy similar to phytanic acid. These metabolites specifically displaced [3H]-9cRA from RXR with Ki values of 4 microM, indicating that their transcriptional effects are mediated by direct receptor interactions. Phytol metabolites are compelling candidates for physiological effectors, because their RXR binding affinities and activation potencies match their micromolar circulating concentrations. Given their exclusive dietary origin, these chlorophyll metabolites may represent essential nutrients that coordinate cellular metabolism through RXR-dependent signaling pathways. PMID:8856661

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.

Nuclear materials 1993 annual report. Volume 8, No. 2

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

NONE

1995-05-01

This annual report of the US Nuclear Regulatory Commission`s Office for Analysis and Evaluation of Operational Data (AEOD) describes activities conducted during 1993. The report is published in two parts. NUREG-1272, Vol. 8, No. 1, covers power reactors and presents an overview of the operating experience of the nuclear power industry from the NRC perspective, including comments about the trends of some key performance measures. The report also includes the principal findings and issues identified in AEOD studies over the past year and summarizes information from such sources as licensee event reports, diagnostic evaluations, and reports to the NRC`s Operationsmore » Center. NUREG-1272, Vol. 8, No. 2, covers nuclear materials and presents a review of the events and concerns during 1993 associated with the use of licensed material in nonreactor applications, such as personnel overexposures and medical misadministrations. Note that the subtitle of No. 2 has been changed from ``Nonreactors`` to ``Nuclear Materials.`` Both reports also contain a discussion of the Incident Investigation Team program and summarize both the Incident Investigation Team and Augmented Inspection Team reports. Each volume contains a list of the AEOD reports issued from 1980 through 1993.« less

Nuclear Data Needs and Capabilities for Applications

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

Brown, D.

2015-05-27

In July 2014, DOE NP carried out a review of the US Nuclear Data Program. This led to several recommendations, including that the USNDP should “devise effective and transparent mechanisms to solicit input and feedback from all stakeholders on nuclear data needs and priorities.” The review also recommended that USNDP pursue experimental activities of relevance to nuclear data; the revised 2014 Mission Statement accordingly states that the USNDP uses “targeted experimental studies” to address gaps in nuclear data. In support of these recommendations, DOE NP requested that USNDP personnel organize a Workshop on Nuclear Data Needs and Capabilities for Applicationsmore » (NDNCA). This Workshop was held at Lawrence Berkeley National Laboratory (LBNL) on 27-29 May 2015. The goal of the NDNCA Workshop was to compile nuclear data needs across a wide spectrum of applied nuclear science, and to provide a summary of associated capabilities (accelerators, reactors, spectrometers, etc.) available for the required measurements. The first two days of the workshop consisted of 25 plenary talks by speakers from 16 different institutions, on nuclear energy (NE), national security (NS), isotope production (IP), and industrial applications (IA). There were also shorter “capabilities” talks that described the experimental facilities and instrumentation available for the measurement of nuclear data. This was followed by a third day of topic-specific “breakout” sessions and a final closeout session. The agenda and copies of these talks are available online at http://bang.berkeley.edu/events/NDNCA/agenda. The importance of nuclear data to both basic and applied nuclear science was reflected in the fact that while the impetus for the workshop arose from the 2014 USNDP review, joint sponsorship for the workshop was provided by the Nuclear Science and Security Consortium, a UC-Berkeley based organization funded by the National Nuclear Security Administration (NNSA).« less

Nuclear Thermal Rocket Element Environmental Simulator (NTREES) Phase II Upgrade Activities

NASA Technical Reports Server (NTRS)

Emrich, William J.; Moran, Robert P.; Pearson, J. Bose

2013-01-01

To support the on-going nuclear thermal propulsion effort, a state-of-the-art non nuclear experimental test setup has been constructed to evaluate the performance characteristics of candidate fuel element materials and geometries in representative environments. The facility to perform this testing is referred to as the Nuclear Thermal Rocket Element Environment Simulator (NTREES). This device can simulate the environmental conditions (minus the radiation) to which nuclear rocket fuel components will be subjected during reactor operation. Test articles mounted in the simulator are inductively heated in such a manner so as to accurately reproduce the temperatures and heat fluxes which would normally occur as a result of nuclear fission and would be exposed to flowing hydrogen. Initial testing of a somewhat prototypical fuel element has been successfully performed in NTREES and the facility has now been shutdown to allow for an extensive reconfiguration of the facility which will result in a significant upgrade in its capabilities. Keywords: Nuclear Thermal Propulsion, Simulator

Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling

PubMed Central

Wilkes, Mark C.; Repellin, Claire E.; Kang, Jeong-Han; Andrianifahanana, Mahefatiana; Yin, Xueqian; Leof, Edward B.

2015-01-01

Transforming growth factor β (TGFβ) is a pleiotropic protein secreted from essentially all cell types and primary tissues. While TGFβ’s actions reflect the activity of a number of signaling networks, the primary mediator of TGFβ responses are the Smad proteins. Following receptor activation, these cytoplasmic proteins form hetero-oligomeric complexes that translocate to the nucleus and affect gene transcription. Here, through biological, biochemical, and immunofluorescence approaches, sorting nexin 9 (SNX9) is identified as being required for Smad3-dependent responses. SNX9 interacts with phosphorylated (p) Smad3 independent of Smad2 or Smad4 and promotes more rapid nuclear delivery than that observed independent of ligand. Although SNX9 does not bind nucleoporins Nup153 or Nup214 or some β importins (Imp7 or Impβ), it mediates the association of pSmad3 with Imp8 and the nuclear membrane. This facilitates nuclear translocation of pSmad3 but not SNX9. PMID:26337383

Development of Scintillators in Nuclear Medicine

PubMed Central

Khoshakhlagh, Mohammad; Islamian, Jalil Pirayesh; Abedi, Seyed Mohammad; Mahmoudian, Babak

2015-01-01

High-quality image is necessary for accurate diagnosis in nuclear medicine. There are many factors in creating a good image and detector is the most important one. In recent years, several detectors are studied to get a better picture. The aim of this paper is comparison of some type of these detectors such as thallium activated sodium iodide bismuth germinate cesium activated yttrium aluminum garnet (YAG: Ce) YAP: Ce “lutetium aluminum garnet activated by cerium” CRY018 “CRY019” lanthanum bromide and cadmium zinc telluride. We studied different properties of these crystals including density, energy resolution and decay times that are more important factors affecting the image quality. PMID:26420984

Nuclear Rocket Technology Conference

NASA Technical Reports Server (NTRS)

1966-01-01

The Lewis Research Center has a strong interest in nuclear rocket propulsion and provides active support of the graphite reactor program in such nonnuclear areas as cryogenics, two-phase flow, propellant heating, fluid systems, heat transfer, nozzle cooling, nozzle design, pumps, turbines, and startup and control problems. A parallel effort has also been expended to evaluate the engineering feasibility of a nuclear rocket reactor using tungsten-matrix fuel elements and water as the moderator. Both of these efforts have resulted in significant contributions to nuclear rocket technology. Many successful static firings of nuclear rockets have been made with graphite-core reactors. Sufficient information has also been accumulated to permit a reasonable Judgment as to the feasibility of the tungsten water-moderated reactor concept. We therefore consider that this technoIogy conference on the nuclear rocket work that has been sponsored by the Lewis Research Center is timely. The conference has been prepared by NASA personnel, but the information presented includes substantial contributions from both NASA and AEC contractors. The conference excludes from consideration the many possible mission requirements for nuclear rockets. Also excluded is the direct comparison of nuclear rocket types with each other or with other modes of propulsion. The graphite reactor support work presented on the first day of the conference was partly inspired through a close cooperative effort between the Cleveland extension of the Space Nuclear Propulsion Office (headed by Robert W. Schroeder) and the Lewis Research Center. Much of this effort was supervised by Mr. John C. Sanders, chairman for the first day of the conference, and by Mr. Hugh M. Henneberry. The tungsten water-moderated reactor concept was initiated at Lewis by Mr. Frank E. Rom and his coworkers. The supervision of the recent engineering studies has been shared by Mr. Samuel J. Kaufman, chairman for the second day of the

Activation of orphan nuclear constitutive androstane receptor requires subnuclear targeting by peroxisome proliferator-activated receptor gamma coactivator-1 alpha. A possible link between xenobiotic response and nutritional state.

PubMed

Shiraki, Takuma; Sakai, Noriko; Kanaya, Eiko; Jingami, Hisato

2003-03-28

In contrast to the classical nuclear receptors, the constitutive androstane receptor (CAR) is transcriptionally active in the absence of ligand. In the course of searching for the mediator of CAR activation, we found that ligand-independent activation of CAR was achieved in cooperation with the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha). PGC-1 beta, a PGC-1 alpha homologue, also activated CAR to less of an extent than PGC-1 alpha. Coexpression of the ligand-binding domain of a heterodimerization partner, retinoid X receptor alpha, enhanced the PGC-1 alpha-mediated activation of CAR, although it had a weak effect on the basal activity of CAR in the absence of PGC-1 alpha. Both the N-terminal region, with the LXXLL motif, and the C-terminal region, with a serine/arginine-rich domain (RS domain), in PGC-1 alpha were required for full activation of CAR. Pull-down experiments using recombinant proteins revealed that CAR directly interacted with both the LXXLL motif and the RS domain. Furthermore, we demonstrated that the RS domain of PGC-1 alpha was required for CAR localization at nuclear speckles. These results indicate that PGC-1 alpha mediates the ligand-independent activation of CAR by means of subnuclear targeting through the RS domain of PGC-1 alpha.

Nuclear Energy, Nuclear Weapons Proliferation, and the Arms Race.

ERIC Educational Resources Information Center

Hollander, Jack, Ed.

A symposium was organized to reexamine the realities of vertical proliferation between the United States and the Soviet Union and to place into perspective the horizontal proliferation of nuclear weapons throughout the world, including the possible role of commercial nuclear power in facilitating proliferation. The four invited symposium…

Regulatory T cells facilitate the nuclear accumulation of inducible cAMP early repressor (ICER) and suppress nuclear factor of activated T cell c1 (NFATc1)

PubMed Central

Vaeth, Martin; Gogishvili, Tea; Bopp, Tobias; Klein, Matthias; Berberich-Siebelt, Friederike; Gattenloehner, Stefan; Avots, Andris; Sparwasser, Tim; Grebe, Nadine; Schmitt, Edgar; Hünig, Thomas; Serfling, Edgar; Bodor, Josef

2011-01-01

Inducible cAMP early repressor (ICER) is a transcriptional repressor, which, because of alternate promoter use, is generated from the 3′ region of the cAMP response modulator (Crem) gene. Its expression and nuclear occurrence are elevated by high cAMP levels in naturally occurring regulatory T cells (nTregs). Using two mouse models, we demonstrate that nTregs control the cellular localization of ICER/CREM, and thereby inhibit IL-2 synthesis in conventional CD4+ T cells. Ablation of nTregs in depletion of regulatory T-cell (DEREG) mice resulted in cytosolic localization of ICER/CREM and increased IL-2 synthesis upon stimulation. Direct contacts between nTregs and conventional CD4+ T cells led to nuclear accumulation of ICER/CREM and suppression of IL-2 synthesis on administration of CD28 superagonistic (CD28SA) Ab. In a similar way, nTregs communicated with B cells and induced the cAMP-driven nuclear localization of ICER/CREM. High levels of ICER suppressed the induction of nuclear factor of activated T cell c1 (Nfatc1) gene in T cells whose inducible Nfatc1 P1 promoter bears two highly conserved cAMP-responsive elements to which ICER/CREM can bind. These findings suggest that nTregs suppress T-cell responses by the cAMP-dependent nuclear accumulation of ICER/CREM and inhibition of NFATc1 and IL-2 induction. PMID:21262800

Research Activities for Nuclear Power Plant Aging Promoted by PLEC, JAPEIC, Japan

NASA Astrophysics Data System (ADS)

Maeda, Noriyoshi; Tajima, Kenichi

In order to perform research activity for aging countermeasure of nuclear power plant effectively, Plant Life Engineering Center (PLEC) was established in Japan Power Engineering and Inspection Corporation (JAPEIC) in April 2000 sponsored by Ministry of International Trade and Industry (MITI, presently METI). Outlined activities of PLEC are as follows. Results of technical survey for research and development for aging phenomena have been summarized in a table (Research Map) categorizing them into “inspection and monitoring”, “evaluation method for aging” and “preventive maintenances and refurbishment”. Necessary research themes have been extracted from the Research Map consulting to experts of the specified research area and they are summarized into Medium and Long-term Research Perspective (Research Perspective), which contains prioritized research themes and outlined specification of each theme. Several new research themes proposed by various organizations and selected by PLEC as effective for the regulation activities are identified and proposed to be funded by METI every year. This paper also provides outlines and obtained results of aging related research projects currently conducted by JAPEIC sponsored by METI.