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Sample records for nuclear transport factors

  1. Thermodynamics of nuclear transport

    NASA Astrophysics Data System (ADS)

    Wang, Ching-Hao; Mehta, Pankaj; Elbaum, Michael

    Molecular transport across the nuclear envelope is important for eukaryotes for gene expression and signaling. Experimental studies have revealed that nuclear transport is inherently a nonequilibrium process and actively consumes energy. In this work we present a thermodynamics theory of nuclear transport for a major class of nuclear transporters that are mediated by the small GTPase Ran. We identify the molecular elements responsible for powering nuclear transport, which we term the ``Ran battery'' and find that the efficiency of transport, measured by the cargo nuclear localization ratio, is limited by competition between cargo molecules and RanGTP to bind transport receptors, as well as the amount of NTF2 (i.e. RanGDP carrier) available to circulate the energy flow. This picture complements our current understanding of nuclear transport by providing a comprehensive thermodynamics framework to decipher the underlying biochemical machinery. Pm and CHW were supported by a Simons Investigator in the Mathematical Modeling in Living Systems grant (to PM).

  2. Interaction of Sp1 zinc finger with transport factor in the nuclear localization of transcription factor Sp1

    SciTech Connect

    Ito, Tatsuo; Kitamura, Haruka; Uwatoko, Chisana; Azumano, Makiko; Itoh, Kohji; Kuwahara, Jun

    2010-12-10

    Research highlights: {yields} Sp1 zinc fingers themselves interact with importin {alpha}. {yields} Sp1 zinc finger domains play an essential role as a nuclear localization signal. {yields} Sp1 can be transported into the nucleus in an importin-dependent manner. -- Abstract: Transcription factor Sp1 is localized in the nucleus and regulates the expression of many cellular genes, but the nuclear transport mechanism of Sp1 is not well understood. In this study, we revealed that GST-fused Sp1 protein bound to endogenous importin {alpha} in HeLa cells via the Sp1 zinc finger domains, which comprise the DNA binding domain of Sp1. It was found that the Sp1 zinc finger domains directly interacted with a wide range of importin {alpha} including the armadillo (arm) repeat domain and the C-terminal acidic domain. Furthermore, it turned out that all three zinc fingers of Sp1 are essential for binding to importin {alpha}. Taken together, these results suggest that the Sp1 zinc finger domains play an essential role as a NLS and Sp1 can be transported into the nucleus in an importin-dependent manner even though it possesses no classical NLSs.

  3. Effects of natural nuclear factor-kappa B inhibitors on anticancer drug efflux transporter human P-glycoprotein.

    PubMed

    Nabekura, Tomohiro; Hiroi, Takashi; Kawasaki, Tatsuya; Uwai, Yuichi

    2015-03-01

    Drug efflux transporter P-glycoprotein plays an important role in cancer chemotherapy. The nuclear factor-κB (NF-κB) transcription factors play critical roles in development and progression of cancer. In this study, the effects of natural compounds that can inhibit NF-κB activation on the function of P-glycoprotein were investigated using human MDR1 gene-transfected KB/MDR1 cells. The accumulation of daunorubicin or rhodamine 123, fluorescent substrates of P-glycoprotein, in KB/MDR1 cells increased in the presence of caffeic acid phenetyl ester (CAPE), licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol in a concentration-dependent manner. In contrast, lupeol, zerumbone, thymoquinone, emodin, and anethol had no effects. The ATPase activities of P-glycoprotein were stimulated by CAPE, licochalcone A, anacardic acid, celastrol, xanthohumol, magnolol, and honokiol. Tumor necrosis factor (TNF)-α stimulated NF-κB activation was inhibited by CAPE, licochalcone A, anacardic acid, and xanthohumol. KB/MDR1 cells were sensitized to vinblastine cytotoxicity by CAPE, licochalcone A, anacardic acid, xanthohumol, magnolol, and honokiol, showing that these natural NF-κB inhibitors reverse multidrug resistance. These results suggest that natural compounds, such as CAPE, licochalcone A, and anacardic acid, have dual inhibitory effects on the anticancer drug efflux transporter P-glycoprotein and NF-κB activation, and may become useful to enhance the efficacy of cancer chemotherapy.

  4. The nuclear pore complex and nuclear transport.

    PubMed

    Wente, Susan R; Rout, Michael P

    2010-10-01

    Internal membrane bound structures sequester all genetic material in eukaryotic cells. The most prominent of these structures is the nucleus, which is bounded by a double membrane termed the nuclear envelope (NE). Though this NE separates the nucleoplasm and genetic material within the nucleus from the surrounding cytoplasm, it is studded throughout with portals called nuclear pore complexes (NPCs). The NPC is a highly selective, bidirectional transporter for a tremendous range of protein and ribonucleoprotein cargoes. All the while the NPC must prevent the passage of nonspecific macromolecules, yet allow the free diffusion of water, sugars, and ions. These many types of nuclear transport are regulated at multiple stages, and the NPC carries binding sites for many of the proteins that modulate and modify the cargoes as they pass across the NE. Assembly, maintenance, and repair of the NPC must somehow occur while maintaining the integrity of the NE. Finally, the NPC appears to be an anchor for localization of many nuclear processes, including gene activation and cell cycle regulation. All these requirements demonstrate the complex design of the NPC and the integral role it plays in key cellular processes. PMID:20630994

  5. Cloning, expression and characterization of the putative nuclear transport factor 2 (NTF2) gene from moss Conocephalum conicum(L.) Dum.

    PubMed

    Bian, Chunxiang; Ruan, Qiping; Peng, Zhengsong; Ji, Hongchun; Jiang, Lichun; Li, Jintao; Yuan, Lijuan

    2011-03-01

    Biomacromolecules import into the nucleus is a complex progress which requires the participation of several cytosolic factors, and nuclear transport factor 2 (NTF2) is one of essential components in nuclear trafficking. Its main role is to transport RanGDP from cytoplasm to nucleus by interacting with FxFG nucleoporin repeats. In the study a putative new gene, designated as CcNTF2, was obtained from the moss (Conocephalum conicum) cDNA library we have constructed. The full-length cDNA sequence is 913 bp in size contains a 372 bp open reading frame (ORF) flanked by a 195 bp 5'-untranslated sequence and a long 346 bp 3'-non-coding region, encoding 123 amino acids of 13,575.3 Da. Part of the genomic sequence was also cloned and sequenced, which is 1,602 bp long and possesses two exons and one intron. Alignment analysis showed that the CcNTF2 protein is high conserved among plant NTF2 and shares 81% similarity with the ones from Arabidopsis thaliana and Brassica rapa. The expression of wild-type CcNTF2 was detected by immunoblotting of extraction of C. conicum and it indicated the putative protein is integral. Through functional expression of CcNTF2-green fluorescent protein (GFP) in tobacco, it was demonstrated that CcNTF2 can accumulate at the nuclear rim. Site-directed mutagenesis analysis confirmed CcNTF2 P71K has influence on the protein import into nucleus. In addition, overexpression of CcNTF2 P71K was observed to be deleterious for the plant cell. It is the first illumination of NTF2 in moss, and our study established the primary foundation for further research on moss NTF2.

  6. Cloning, expression and characterization of the putative nuclear transport factor 2 (NTF2) gene from moss Conocephalum conicum(L.) Dum.

    PubMed

    Bian, Chunxiang; Ruan, Qiping; Peng, Zhengsong; Ji, Hongchun; Jiang, Lichun; Li, Jintao; Yuan, Lijuan

    2011-03-01

    Biomacromolecules import into the nucleus is a complex progress which requires the participation of several cytosolic factors, and nuclear transport factor 2 (NTF2) is one of essential components in nuclear trafficking. Its main role is to transport RanGDP from cytoplasm to nucleus by interacting with FxFG nucleoporin repeats. In the study a putative new gene, designated as CcNTF2, was obtained from the moss (Conocephalum conicum) cDNA library we have constructed. The full-length cDNA sequence is 913 bp in size contains a 372 bp open reading frame (ORF) flanked by a 195 bp 5'-untranslated sequence and a long 346 bp 3'-non-coding region, encoding 123 amino acids of 13,575.3 Da. Part of the genomic sequence was also cloned and sequenced, which is 1,602 bp long and possesses two exons and one intron. Alignment analysis showed that the CcNTF2 protein is high conserved among plant NTF2 and shares 81% similarity with the ones from Arabidopsis thaliana and Brassica rapa. The expression of wild-type CcNTF2 was detected by immunoblotting of extraction of C. conicum and it indicated the putative protein is integral. Through functional expression of CcNTF2-green fluorescent protein (GFP) in tobacco, it was demonstrated that CcNTF2 can accumulate at the nuclear rim. Site-directed mutagenesis analysis confirmed CcNTF2 P71K has influence on the protein import into nucleus. In addition, overexpression of CcNTF2 P71K was observed to be deleterious for the plant cell. It is the first illumination of NTF2 in moss, and our study established the primary foundation for further research on moss NTF2. PMID:20857212

  7. The pro-inflammatory cytokine tumor necrosis factor α stimulates expression of the carnitine transporter OCTN2 (novel organic cation transporter 2) and carnitine uptake via nuclear factor-κB in Madin-Darby bovine kidney cells.

    PubMed

    Zhou, X; Ringseis, R; Wen, G; Eder, K

    2015-06-01

    Carnitine uptake into tissues is mediated mainly by the novel organic cation transporter 2 (OCTN2), whose expression is upregulated in the liver of early-lactating dairy cows. It has been shown recently that pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), stimulate OCTN2 expression and carnitine uptake in intestinal cells and inflamed intestinal mucosa. Given that many early-lactating dairy cows show typical signs of hepatic and systemic inflammation, such as elevated concentrations of circulating TNFα and activation of the key regulator of inflammation, nuclear factor κB (NF-κB), in tissues, it is possible that upregulation of OCTN2 and increase of carnitine uptake by TNFα is mediated by NF-κB, a mechanism that might contribute to the upregulation of OCNT2 in the liver of early-lactating dairy cows. Thus, in the present study, we tested the hypothesis that TNFα stimulates OCTN2 gene expression and carnitine uptake via NF-κB in the bovine Madin-Darby bovine kidney (MDBK) cell line. Treatment with TNFα caused activation of NF-κB, increased the mRNA and protein concentration of OCTN2, and stimulated the uptake of carnitine in MDBK cells. In contrast, combined treatment of MDBK cells with TNFα and the NF-κB inhibitor BAY 11-7085 completely blocked the effect of TNFα on OCTN2 mRNA and protein concentration and uptake of carnitine. These findings suggest that the bovine OCTN2 gene and carnitine uptake are regulated by NF-κB. Future studies are required to show the in vivo relevance of this regulatory mechanism in cattle.

  8. Rab7 Mutants Associated with Charcot-Marie-Tooth Disease Cause Delayed Growth Factor Receptor Transport and Altered Endosomal and Nuclear Signaling*

    PubMed Central

    BasuRay, Soumik; Mukherjee, Sanchita; Romero, Elsa G.; Seaman, Matthew N. J.; Wandinger-Ness, Angela

    2013-01-01

    Rab7 belongs to the Ras superfamily of small GTPases and is a master regulator of early to late endocytic membrane transport. Four missense mutations in the late endosomal Rab7 GTPase (L129F, K157N, N161T, and V162M) cause the autosomal dominant peripheral neuropathy Charcot-Marie-Tooth type 2B (CMT2B) disease. As yet, the pathological mechanisms connecting mutant Rab7 protein expression to altered neuronal function are undefined. Here, we analyze the effects of Rab7 CMT2B mutants on epidermal growth factor (EGF)-dependent intracellular signaling and trafficking. Three different cell lines expressing Rab7 CMT2B mutants and stimulated with EGF exhibited delayed trafficking of EGF to LAMP1-positive late endosomes and lysosomes and slowed EGF receptor (EGFR) degradation. Expression of all Rab7 CMT2B mutants altered the Rab7 activation cycle, leading to enhanced and prolonged EGFR signaling as well as variable increases in p38 and ERK1/2 activation. However, due to reduced nuclear translocation of p38 and ERK1/2, the downstream nuclear activation of Elk-1 was decreased along with the expression of immediate early genes like c-fos and Egr-1 by the disease mutants. In conclusion, our results demonstrate that Rab7 CMT2B mutants impair growth factor receptor trafficking and, in turn, alter p38 and ERK1/2 signaling from perinuclear, clustered signaling endosomes. The resulting down-regulation of EGFR-dependent nuclear transcription that is crucial for normal axon outgrowth and peripheral innervation offers a crucial new mechanistic insight into disease pathogenesis that is relevant to other neurodegenerative diseases. PMID:23188822

  9. Directional Phosphorylation and Nuclear Transport of the Splicing Factor SRSF1 Is Regulated by an RNA Recognition Motif.

    PubMed

    Serrano, Pedro; Aubol, Brandon E; Keshwani, Malik M; Forli, Stefano; Ma, Chen-Ting; Dutta, Samit K; Geralt, Michael; Wüthrich, Kurt; Adams, Joseph A

    2016-06-01

    Multisite phosphorylation is required for the biological function of serine-arginine (SR) proteins, a family of essential regulators of mRNA splicing. These modifications are catalyzed by serine-arginine protein kinases (SRPKs) that phosphorylate numerous serines in arginine-serine-rich (RS) domains of SR proteins using a directional, C-to-N-terminal mechanism. The present studies explore how SRPKs govern this highly biased phosphorylation reaction and investigate biological roles of the observed directional phosphorylation mechanism. Using NMR spectroscopy with two separately expressed domains of SRSF1, we showed that several residues in the RNA-binding motif 2 interact with the N-terminal region of the RS domain (RS1). These contacts provide a structural framework that balances the activities of SRPK1 and the protein phosphatase PP1, thereby regulating the phosphoryl content of the RS domain. Disruption of the implicated intramolecular RNA-binding motif 2-RS domain interaction impairs both the directional phosphorylation mechanism and the nuclear translocation of SRSF1 demonstrating that the intrinsic phosphorylation bias is obligatory for SR protein biological function. PMID:27091468

  10. Hepatocyte Nuclear Factor 1 Regulates the Expression of the Organic Cation Transporter 1 via Binding to an Evolutionary Conserved Region in Intron 1 of the OCT1 Gene

    PubMed Central

    O’Brien, Valerie P.; Bokelmann, Kristin; Ramírez, Jacqueline; Jobst, Karoline; Ratain, Mark J.; Brockmöller, Jürgen

    2013-01-01

    The organic cation transporter 1 (OCT1), also known as solute carrier family 22 member 1, is strongly and specifically expressed in the human liver. Here we show that the hepatocyte nuclear factor 1 (HNF1) regulates OCT1 transcription and contributes to the strong, liver-specific expression of OCT1. Bioinformatic analyses revealed strong conservation of HNF1 binding motifs in an evolutionary conserved region (ECR) in intron 1 of the OCT1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the specific binding of HNF1 to the intron 1 ECR. In reporter gene assays performed in HepG2 cells, the intron 1 ECR increased SV40 promoter activity by 22-fold and OCT1 promoter activity by 13-fold. The increase was reversed when the HNF1 binding sites in the intron 1 ECR were mutated or the endogenous HNF1α expression was downregulated with small interfering RNA. Following HNF1α overexpression in Huh7 cells, the intron 1 ECR increased SV40 promoter activity by 11-fold and OCT1 promoter activity by 6-fold. Without HNF1α overexpression, the increases were only 3- and 2-fold, respectively. Finally, in human liver samples, high HNF1 expression was significantly correlated with high OCT1 expression (r = 0.48, P = 0.002, n = 40). In conclusion, HNF1 is a strong regulator of OCT1 expression. It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin. Beyond OCT1, this study demonstrates the validity and usefulness of interspecies comparisons in the discovery of functionally relevant genomic sequences. PMID:23922447

  11. The Yeast Nuclear Pore Complex and Transport Through It

    PubMed Central

    Aitchison, John D.; Rout, Michael P.

    2012-01-01

    Exchange of macromolecules between the nucleus and cytoplasm is a key regulatory event in the expression of a cell’s genome. This exchange requires a dedicated transport system: (1) nuclear pore complexes (NPCs), embedded in the nuclear envelope and composed of proteins termed nucleoporins (or “Nups”), and (2) nuclear transport factors that recognize the cargoes to be transported and ferry them across the NPCs. This transport is regulated at multiple levels, and the NPC itself also plays a key regulatory role in gene expression by influencing nuclear architecture and acting as a point of control for various nuclear processes. Here we summarize how the yeast Saccharomyces has been used extensively as a model system to understand the fundamental and highly conserved features of this transport system, revealing the structure and function of the NPC; the NPC’s role in the regulation of gene expression; and the interactions of transport factors with their cargoes, regulatory factors, and specific nucleoporins. PMID:22419078

  12. Targeting the β-catenin nuclear transport pathway in cancer.

    PubMed

    Jamieson, Cara; Sharma, Manisha; Henderson, Beric R

    2014-08-01

    The nuclear localization of specific proteins is critical for cellular processes such as cell division, and in recent years perturbation of the nuclear transport cycle of key proteins has been linked to cancer. In particular, specific gene mutations can alter nuclear transport of tumor suppressing and oncogenic proteins, leading to cell transformation or cancer progression. This review will focus on one such factor, β-catenin, a key mediator of the canonical wnt signaling pathway. In response to a wnt stimulus or specific gene mutations, β-catenin is stabilized and translocates to the nucleus where it binds TCF/LEF-1 transcription factors to transactivate genes that drive tumor formation. Moreover, the nuclear import and accumulation of β-catenin correlates with clinical tumor grade. Recent evidence suggests that the primary nuclear transport route of β-catenin is independent of the classical Ran/importin import machinery, and that β-catenin directly contacts the nuclear pore complex to self-regulate its own entry into the nucleus. Here we propose that the β-catenin nuclear import pathway may provide an opportunity for identification of specific drug targets and inhibition of β-catenin nuclear function, much like the current screening of drugs that block binding of β-catenin to LEF-1/TCFs. Here we will discuss the diverse mechanisms regulating nuclear localization of β-catenin and their potential as targets for anticancer agent development. PMID:24820952

  13. Nuclear transportation: The global vision

    SciTech Connect

    Lowry, D.; Blowers, A.

    1996-12-31

    The movement of nuclear materials - spent fuel, plutonium and uranium and radioactive wastes - has become an issue of international political significance. It has generated considerable attention from a developing network of NGOs focussing on movements between France and Japan. The paper discusses the conflicts and their implications for six basic principles of radioactive waste management.

  14. Components and regulation of nuclear transport processes.

    PubMed

    Cautain, Bastien; Hill, Richard; de Pedro, Nuria; Link, Wolfgang

    2015-02-01

    The spatial separation of DNA replication and gene transcription in the nucleus and protein translation in the cytoplasm is a uniform principle of eukaryotic cells. This compartmentalization imposes a requirement for a transport network of macromolecules to shuttle these components in and out of the nucleus. This nucleo-cytoplasmic transport of macromolecules is critical for both cell physiology and pathology. Consequently, investigating its regulation and disease-associated alterations can reveal novel therapeutic approaches to fight human diseases, such as cancer or viral infection. The characterization of the nuclear pore complex, the identification of transport signals and transport receptors, as well as the characterization of the Ran system (providing the energy source for efficient cargo transport) has greatly facilitated our understanding of the components, mechanisms and regulation of the nucleo-cytoplasmic transport of proteins in our cells. Here we review this knowledge with a specific emphasis on the selection of disease-relevant molecular targets for potential therapeutic intervention.

  15. Atoms on the Move: Transporting Nuclear Material.

    ERIC Educational Resources Information Center

    Dukert, Joseph M.

    This is an Energy Research and Development Administration pamphlet outlining in detail the many aspects involved in safe transportation of all types of nuclear materials. The detailed safety regulations and designs of various shipping packages and containers are emphasized. Included are maps of waste burial sites and fuel production facilities, an…

  16. Energetics of Transport through the Nuclear Pore Complex

    PubMed Central

    Ghavami, Ali; van der Giessen, Erik; Onck, Patrick R.

    2016-01-01

    Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex (NPC). The NPC provides two types of nucleocytoplasmic transport: passive diffusion of small molecules and active chaperon-mediated translocation of large molecules. It has been shown that the interaction between intrinsically disordered proteins that line the central channel of the NPC and the transporting cargoes is the determining factor, but the exact mechanism of transport is yet unknown. Here, we use coarse-grained molecular dynamics simulations to quantify the energy barrier that has to be overcome for molecules to pass through the NPC. We focus on two aspects of transport. First, the passive transport of model cargo molecules with different sizes is studied and the size selectivity feature of the NPC is investigated. Our results show that the transport probability of cargoes is significantly reduced when they are larger than ∼5 nm in diameter. Secondly, we show that incorporating hydrophobic binding spots on the surface of the cargo effectively decreases the energy barrier of the pore. Finally, a simple transport model is proposed which characterizes the energy barrier of the NPC as a function of diameter and hydrophobicity of the transporting particles. PMID:26894898

  17. Energetics of Transport through the Nuclear Pore Complex.

    PubMed

    Ghavami, Ali; van der Giessen, Erik; Onck, Patrick R

    2016-01-01

    Molecular transport across the nuclear envelope in eukaryotic cells is solely controlled by the nuclear pore complex (NPC). The NPC provides two types of nucleocytoplasmic transport: passive diffusion of small molecules and active chaperon-mediated translocation of large molecules. It has been shown that the interaction between intrinsically disordered proteins that line the central channel of the NPC and the transporting cargoes is the determining factor, but the exact mechanism of transport is yet unknown. Here, we use coarse-grained molecular dynamics simulations to quantify the energy barrier that has to be overcome for molecules to pass through the NPC. We focus on two aspects of transport. First, the passive transport of model cargo molecules with different sizes is studied and the size selectivity feature of the NPC is investigated. Our results show that the transport probability of cargoes is significantly reduced when they are larger than ∼5 nm in diameter. Secondly, we show that incorporating hydrophobic binding spots on the surface of the cargo effectively decreases the energy barrier of the pore. Finally, a simple transport model is proposed which characterizes the energy barrier of the NPC as a function of diameter and hydrophobicity of the transporting particles.

  18. Spent Nuclear Fuel Transport Reliability Study

    SciTech Connect

    Wang, Jy-An John; Wang, Hong; Jiang, Hao

    2016-01-01

    This conference paper was orignated and shorten from the following publisehd PTS documents: 1. Jy-An Wang, Hao Jiang, and Hong Wang, Dynamic Deformation Simulation of Spent Nuclear Fuel Assembly and CIRFT Deformation Sensor Stability Investigation, ORNL/SPR-2015/662, November 2015. 2. Jy-An Wang, Hong Wang, Mechanical Fatigue Testing of High-Burnup Fuel for Transportation Applications, NUREG/CR-7198, ORNL/TM-2014/214, May 2015. 3. Jy-An Wang, Hong Wang, Hao Jiang, Yong Yan, Bruce Bevard, Spent Nuclear Fuel Vibration Integrity Study 16332, WM2016 Conference, March 6 10, 2016, Phoenix, Arizona.

  19. Human Factors Research and Nuclear Safety.

    ERIC Educational Resources Information Center

    Moray, Neville P., Ed.; Huey, Beverly M., Ed.

    The Panel on Human Factors Research Needs in Nuclear Regulatory Research was formed by the National Research Council in response to a request from the Nuclear Regulatory Commission (NRC). The NRC asked the research council to conduct an 18-month study of human factors research needs for the safe operation of nuclear power plants. This report…

  20. Transport-theoretical description of nuclear reactions

    NASA Astrophysics Data System (ADS)

    Buss, O.; Gaitanos, T.; Gallmeister, K.; van Hees, H.; Kaskulov, M.; Lalakulich, O.; Larionov, A. B.; Leitner, T.; Weil, J.; Mosel, U.

    2012-03-01

    In this review we first outline the basics of transport theory and its recent generalization to off-shell transport. We then present in some detail the main ingredients of any transport method using in particular the Giessen Boltzmann-Uehling-Uhlenbeck (GiBUU) implementation of this theory as an example. We discuss the potentials used, the ground state initialization and the collision term, including the in-medium modifications of the latter. The central part of this review covers applications of GiBUU to a wide class of reactions, starting from pion-induced reactions over proton and antiproton reactions on nuclei to heavy-ion collisions (up to about 30 AGeV). A major part concerns also the description of photon-, electron- and neutrino-induced reactions (in the energy range from a few 100 MeV to a few 100 GeV). For this wide class of reactions GiBUU gives an excellent description with the same physics input and the same code being used. We argue that GiBUU is an indispensable tool for any investigation of nuclear reactions in which final-state interactions play a role. Studies of pion-nucleus interactions, nuclear fragmentation, heavy-ion reactions, hypernucleus formation, hadronization, color transparency, electron-nucleus collisions and neutrino-nucleus interactions are all possible applications of GiBUU and are discussed in this article.

  1. Astrocyte elevated gene-1 is a novel modulator of HIV-1-associated neuroinflammation via regulation of nuclear factor-κB signaling and excitatory amino acid transporter-2 repression.

    PubMed

    Vartak-Sharma, Neha; Gelman, Benjamin B; Joshi, Chaitanya; Borgamann, Kathleen; Ghorpade, Anuja

    2014-07-11

    Astrocyte elevated gene-1 (AEG-1), a novel human immunodeficiency virus (HIV)-1 and tumor necrosis factor (TNF)-α-inducible oncogene, has generated significant interest in the field of cancer research as a therapeutic target for many metastatic aggressive tumors. However, little is known about its role in astrocyte responses during HIV-1 central nervous system (CNS) infection and whether it contributes toward the development of HIV-associated neurocognitive disorders (HAND). Therefore, in this study, we investigated changes in AEG-1 CNS expression in HIV-1-infected brain tissues and elucidated a potential mechanism of AEG-1-mediated regulation of HAND. Immunoblotting and immunohistochemical analyses of HIV-1 seropositive and HIV-1 encephalitic human brain tissues revealed significantly elevated levels of AEG-1 protein. Immunohistochemical analyses of HIV-1 Tat transgenic mouse brain tissues also showed a marked increase in AEG-1 staining. Similar to in vivo observations, cultured astrocytes expressing HIV-1 Tat also revealed AEG-1 and cytokine up-regulation. Astrocytes treated with HAND-relevant stimuli, TNF-α, interleukin (IL)-1β, and HIV-1, also significantly induced AEG-1 expression and nuclear translocation via activation of the nuclear factor (NF)-κB pathway. Co-immunoprecipitation studies demonstrated IL-1β- or TNF-α-induced AEG-1 interaction with NF-κB p65 subunit. AEG-1 knockdown decreased NF-κB activation, nuclear translocation, and transcriptional output in TNF-α-treated astrocytes. Moreover, IL-1β treatment of AEG-1-overexpressing astrocytes significantly lowered expression of excitatory amino acid transporter 2, increased expression of excitatory amino acid transporter 2 repressor ying yang 1, and reduced glutamate clearance, a major transducer of excitotoxic neuronal damage. Findings from this study identify a novel transcriptional co-factor function of AEG-1 and further implicate AEG-1 in HAND-associated neuroinflammation.

  2. Nuclear Energy and Synthetic Liquid Transportation Fuels

    NASA Astrophysics Data System (ADS)

    McDonald, Richard

    2012-10-01

    This talk will propose a plan to combine nuclear reactors with the Fischer-Tropsch (F-T) process to produce synthetic carbon-neutral liquid transportation fuels from sea water. These fuels can be formed from the hydrogen and carbon dioxide in sea water and will burn to water and carbon dioxide in a cycle powered by nuclear reactors. The F-T process was developed nearly 100 years ago as a method of synthesizing liquid fuels from coal. This process presently provides commercial liquid fuels in South Africa, Malaysia, and Qatar, mainly using natural gas as a feedstock. Nuclear energy can be used to separate water into hydrogen and oxygen as well as to extract carbon dioxide from sea water using ion exchange technology. The carbon dioxide and hydrogen react to form synthesis gas, the mixture needed at the beginning of the F-T process. Following further refining, the products, typically diesel and Jet-A, can use existing infrastructure and can power conventional engines with little or no modification. We can then use these carbon-neutral liquid fuels conveniently long into the future with few adverse environmental impacts.

  3. Ion transport of Fr nuclear reaction products

    SciTech Connect

    Behr, J.A.; Cahn, S.B.; Dutta, S.B.

    1993-04-01

    Experiments planned for fundamental studies of radioactive atoms in magneto-optic traps require efficient deceleration and transport of nuclear reaction products to energies and locations where they can be trapped. The authors have built a low-energy ion transport system for Francium and other alkalis. A thick Au target is held on a W rod at 45{degrees} to the accelerator beam direction. The heavy-ion fusion reaction 115 MeV {sup 18}O + {sup 197}Au produces {sup 211,210,209}Fr recoil products which are stopped in the target. The target is heated to close to the melting point of Au to allow the Fr to diffuse to the surface, where it is ionized due to Au`s high work function, and is directly extracted by an electrode at 90{degrees} to the accelerator beam direction. The Fr is transported by electrostatic optics {approximately}1 m to a catcher viewed by an {alpha} detector: {ge}15% of the Fr produced in the target reaches the catcher. 2{times}10{sup 5} Fr/sec have been produced at the catcher, yielding at equilibrium a sample of 3x10{sup 7}Fr nuclei. This scheme physically decouples the target diffusion from the surface neutralization process, which can occur at a lower temperature more compatible with the neutral-atom trap.

  4. Nuclear transport erupts on the slopes of Mount Etna.

    PubMed

    Powers, Maureen A; Dasso, Mary

    2004-02-01

    Nuclear pore complexes (NPCs) mediate the active transport of large substrates and allow the passive diffusion of small molecules into the nucleus of eukaryotic cells. The EMBO Workshop on the Mechanisms of Nuclear Transport focused on NPCs and on the soluble nucleocytoplasmic transport machinery. This meeting, organized by Valérie Doye (Institut Curie, Paris) and Ed Hurt (University of Heidelberg), was held within view of Mount Etna at Taormina, Sicily (November 1-5, 2003). Presentations emphasized the dynamic properties of the nuclear trafficking machinery, and demonstrated the continuity of nuclear transport with processes in the nucleus and cytoplasm.

  5. Spatiotemporal Regulation of Nuclear Transport Machinery and Microtubule Organization

    PubMed Central

    Okada, Naoyuki; Sato, Masamitsu

    2015-01-01

    Spindle microtubules capture and segregate chromosomes and, therefore, their assembly is an essential event in mitosis. To carry out their mission, many key players for microtubule formation need to be strictly orchestrated. Particularly, proteins that assemble the spindle need to be translocated at appropriate sites during mitosis. A small GTPase (hydrolase enzyme of guanosine triphosphate), Ran, controls this translocation. Ran plays many roles in many cellular events: nucleocytoplasmic shuttling through the nuclear envelope, assembly of the mitotic spindle, and reorganization of the nuclear envelope at the mitotic exit. Although these events are seemingly distinct, recent studies demonstrate that the mechanisms underlying these phenomena are substantially the same as explained by molecular interplay of the master regulator Ran, the transport factor importin, and its cargo proteins. Our review focuses on how the transport machinery regulates mitotic progression of cells. We summarize translocation mechanisms governed by Ran and its regulatory proteins, and particularly focus on Ran-GTP targets in fission yeast that promote spindle formation. We also discuss the coordination of the spatial and temporal regulation of proteins from the viewpoint of transport machinery. We propose that the transport machinery is an essential key that couples the spatial and temporal events in cells. PMID:26308057

  6. Palmitate-induced interleukin 6 production is mediated by protein kinase C and nuclear-factor kappaB activation and leads to glucose transporter 4 down-regulation in skeletal muscle cells.

    PubMed

    Jové, Mireia; Planavila, Anna; Laguna, Juan Carlos; Vázquez-Carrera, Manuel

    2005-07-01

    The mechanisms by which elevated levels of free fatty acids cause insulin resistance are not well understood. In addition, accumulating evidence suggests a link between inflammation and type 2 diabetes. Here, we report that exposure of C2C12 skeletal muscle cells to 0.5 mm palmitate results in increased mRNA levels (3.5-fold induction; P < 0.05) and secretion (control 375 +/- 57 vs. palmitate 1129 +/- 177 pg/ml; P < 0.001) of the proinflammatory cytokine IL-6. Palmitate increased nuclear factor-kappaB activation and coincubation of the cells with palmitate and the nuclear factor-kappaB inhibitor pyrrolidine dithiocarbamate prevented both IL-6 expression and secretion. Furthermore, incubation of palmitate-treated cells with calphostin C, a strong and specific inhibitor of protein kinase C, and phorbol myristate acetate, that down-regulates protein kinase C in long-term incubations, abolished induction of IL-6 production. Finally, exposure of skeletal muscle cells to palmitate caused a fall in the mRNA levels of glucose transporter 4 and insulin-stimulated glucose uptake, whereas in the presence of anti-IL-6 antibody, which neutralizes the biological activity of mouse IL-6 in cell culture, these reductions were prevented. These findings suggest that IL-6 may mediate several of the prodiabetic effects of palmitate.

  7. Identification of four nuclear transport signal-binding proteins that interact with diverse transport signals.

    PubMed

    Yamasaki, L; Kanda, P; Lanford, R E

    1989-07-01

    The transport of proteins into the nucleus requires not only the presence of a nuclear transport signal on the targeted protein but also the signal recognition proteins and the nuclear pore translocation apparatus. Complicating the search for the signal recognition proteins is the fact that the nuclear transport signals identified share little obvious homology. In this study, synthetic peptides homologous to the nuclear transport signals from the simian virus 40 large T antigen, Xenopus oocyte nucleoplasmin, adenovirus E1A, and Saccharomyces cerevisiae MAT alpha 2 proteins were coupled to a UV-photoactivable cross-linker and iodinated for use in an in vitro cross-linking reaction with cellular lysates. Four proteins, p140, p100, p70, and p55, which specifically interacted with the nuclear transport signal peptides were identified. Unique patterns of reactivity were observed with closely related pairs of nuclear transport signal peptides. Competition experiments with labeled and unlabeled peptides demonstrated that heterologous signals were able to bind the same protein and suggested that diverse signals use a common transport pathway. The subcellular distribution of the four nuclear transport signal-binding proteins suggested that nuclear transport involves both cytoplasmic and nuclear receptors. The four proteins were not bound by wheat germ agglutinin and were not associated tightly with the nuclear pore complex.

  8. Nuclear protein accumulation by facilitated transport and intranuclear binding.

    PubMed

    Paine, P L

    1993-10-01

    Nuclear proteins are transported from the cytoplasm into the nucleus via nuclear envelope pore complexes (NPCs). At the molecular level, the mechanisms responsible for this transport remain obscure. However, it is known that, for many proteins, the process requires ATP and proceeds against formidable nucleocytoplasmic concentration gradients. Therefore, the NPC is often thought of as an active transport site. In this article, Philip Paine presents the alternative hypothesis that, on current evidence, protein translocation across the nuclear envelope and accumulation in the nucleus can equally well be explained by facilitated transport through the NPC and subsequent intranuclear binding.

  9. Kpna7 interacts with egg-specific nuclear factors in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nuclear proteins are required for initiation of transcription in early embryos before embryonic genome activation. The regulation of transportation of nuclear proteins is mediated by transport factors known as importins (karyopherins). Kpna7 is a newly discovered member of the importin a family, whi...

  10. The motion commotion: Human factors in transportation

    NASA Technical Reports Server (NTRS)

    Millar, A. E., Jr. (Editor); Rosen, R. L. (Editor); Gibson, J. D. (Editor); Crum, R. G. (Editor)

    1972-01-01

    The program for a systems approach to the problem of incorporating human factors in designing transportation systems is summarized. The importance of the human side of transportation is discussed along with the three major factors related to maintaining a mobile and quality life. These factors are (1) people, as individuals and groups, (2) society as a whole, and (3) the natural environment and man-made environs. The problems and bottlenecks are presented along with approaches to their solutions through systems analysis. Specific recommendations essential to achieving improved mobility within environmental constraints are presented.

  11. Factorized molecular wave functions: Analysis of the nuclear factor

    SciTech Connect

    Lefebvre, R.

    2015-06-07

    The exact factorization of molecular wave functions leads to nuclear factors which should be nodeless functions. We reconsider the case of vibrational perturbations in a diatomic species, a situation usually treated by combining Born-Oppenheimer products. It was shown [R. Lefebvre, J. Chem. Phys. 142, 074106 (2015)] that it is possible to derive, from the solutions of coupled equations, the form of the factorized function. By increasing artificially the interstate coupling in the usual approach, the adiabatic regime can be reached, whereby the wave function can be reduced to a single product. The nuclear factor of this product is determined by the lowest of the two potentials obtained by diagonalization of the potential matrix. By comparison with the nuclear wave function of the factorized scheme, it is shown that by a simple rectification, an agreement is obtained between the modified nodeless function and that of the adiabatic scheme.

  12. Enzymatically driven transport: a kinetic theory for nuclear export.

    PubMed

    Kim, Sanghyun; Elbaum, M

    2013-11-01

    Nuclear import and export are often considered inverse processes whereby transport receptors ferry protein cargo through the nuclear pore. In contrast to import, where the reversible binding of receptor to nuclear RanGTP leads to a balanced bidirectional exchange, termination of export by physiologically irreversible hydrolysis of the Ran-bound GTP leads to unidirectional transport. We present a concise mathematical model that predicts protein distributions and kinetic rates for receptor-mediated nuclear export, which further exhibit an unexpected pseudolinear relation one to the other. Predictions of the model are verified with permeabilized and live cell measurements.

  13. Interaction with plant transcription factors can mediate nuclear import of phytochrome B.

    PubMed

    Pfeiffer, Anne; Nagel, Marie-Kristin; Popp, Claudia; Wüst, Florian; Bindics, János; Viczián, András; Hiltbrunner, Andreas; Nagy, Ferenc; Kunkel, Tim; Schäfer, Eberhard

    2012-04-10

    Phytochromes (phy) are red/far-red-absorbing photoreceptors that regulate the adaption of plant growth and development to changes in ambient light conditions. The nuclear transport of the phytochromes upon light activation is regarded as a key step in phytochrome signaling. Although nuclear import of phyA is regulated by the transport facilitators far red elongated hypocotyl 1 (FHY1) and fhy1-like, an intrinsic nuclear localization signal was proposed to be involved in the nuclear accumulation of phyB. We recently showed that nuclear import of phytochromes can be analyzed in a cell-free system consisting of isolated nuclei of the unicellular green algae Acetabularia acetabulum. We now show that this system is also versatile to elucidate the mechanism of the nuclear transport of phyB. We tested the nuclear transport characteristics of full-length phyB as well as N- and C-terminal phyB fragments in vitro and showed that the nuclear import of phyB can be facilitated by phytochrome-interacting factor 3 (PIF3). In vivo measurements of phyB nuclear accumulation in the absence of PIF1, -3, -4, and -5 indicate that these PIFs are the major transport facilitators during the first hours of deetiolation. Under prolonged irradiations additional factors might be responsible for phyB nuclear transport in the plant.

  14. Comparative analyses of spent nuclear fuel transport modal options: Transport options under existing site constraints

    SciTech Connect

    Brentlinger, L.A.; Hofmann, P.L.; Peterson, R.W.

    1989-08-01

    The movement of nuclear waste can be accomplished by various transport modal options involving different types of vehicles, transport casks, transport routes, and intermediate intermodal transfer facilities. A series of systems studies are required to evaluate modal/intermodal spent fuel transportation options in a consistent fashion. This report provides total life-cycle cost and life-cycle dose estimates for a series of transport modal options under existing site constraints. 14 refs., 7 figs., 28 tabs.

  15. Effects of Nuclear Interactions in Space Radiation Transport

    NASA Technical Reports Server (NTRS)

    Lin, Zi-Wei; Barghouty, A. F.

    2005-01-01

    Space radiation transport codes have been developed to calculate radiation effects behind materials in human mission to the Moon, Mars or beyond. We study how nuclear fragmentation processes affect predictions from such radiation transport codes. In particular, we investigate the effects of fragmentation cross sections at different energies on fluxes, dose and dose-equivalent from galactic cosmic rays behind typical shielding materials.

  16. Effects of Nuclear Interactions in Space Radiation Transport

    NASA Technical Reports Server (NTRS)

    Lin, Zi-Wei; Barghouty, A. F.

    2004-01-01

    Space radiation transport codes have been developed to calculate radiation effects behind materials in human missions to the Moon, Mars or beyond. We study how nuclear fragmentation processes affect predictions from such radiation transport codes. In particular, we investigate the effects of fragmentation cross sections at different energies on fluxes, dose and dose-equivalent from galactic cosmic rays behind typical shielding materials.

  17. Electron transport through nuclear pasta in magnetized neutron stars

    NASA Astrophysics Data System (ADS)

    Yakovlev, D. G.

    2015-10-01

    We present a simple model for electron transport in a possible layer of exotic nuclear clusters (in the so-called nuclear pasta layer) between the crust and liquid core of a strongly magnetized neutron star. The electron transport there can be strongly anisotropic and gyrotropic. The anisotropy is produced by different electron effective collision frequencies along and across local symmetry axis in domains of exotic ordered nuclear clusters and by complicated effects of the magnetic field. We also calculate averaged kinetic coefficients in case local domains are freely oriented. Possible applications of the obtained results and open problems are outlined.

  18. Review of EPRI Nuclear Human Factors Program

    SciTech Connect

    Hanes, L.F.; O`Brien, J.F.

    1996-03-01

    The Electric Power Research Institute (EPRI) Human Factors Program, which is part of the EPRI Nuclear Power Group, was established in 1975. Over the years, the Program has changed emphasis based on the shifting priorities and needs of the commercial nuclear power industry. The Program has produced many important products that provide significant safety and economic benefits for EPRI member utilities. This presentation will provide a brief history of the Program and products. Current projects and products that have been released recently will be mentioned.

  19. Transportation capabilities study of DOE-owned spent nuclear fuel

    SciTech Connect

    Clark, G.L.; Johnson, R.A.; Smith, R.W.; Abbott, D.G.; Tyacke, M.J.

    1994-10-01

    This study evaluates current capabilities for transporting spent nuclear fuel owned by the US Department of Energy. Currently licensed irradiated fuel shipping packages that have the potential for shipping the spent nuclear fuel are identified and then matched against the various spent nuclear fuel types. Also included are the results of a limited investigation into other certified packages and new packages currently under development. This study is intended to support top-level planning for the disposition of the Department of Energy`s spent nuclear fuel inventory.

  20. The transport of nuclear power plant components. [via airships

    NASA Technical Reports Server (NTRS)

    Keating, S. J., Jr.

    1975-01-01

    The problems of transporting nuclear power plant components to landlocked sites where the usual mode of transport by barge cannot be used are considered. Existing methods of ground-based overland transport are discussed and their costs presented. Components are described and traffic density projections made to the year 2000. Plots of units transported versus distance transported are provided for units booked in 1973 and booked and proposed in 1974. It is shown that, for these cases, overland transport requirements for the industry will be over 5,000,000 ton-miles/year while a projection based on increasing energy demands shows that this figure will increase significantly by the year 2000. The payload size, distances, and costs of existing overland modes are significant enough to consider development of a lighter than air (LTA) mode for transporting NSSS components.

  1. Effects of Nuclear Interactions on Accuracy of Space Radiation Transport

    NASA Technical Reports Server (NTRS)

    Lin, Zi-Wei; Barghouty, A. F.

    2005-01-01

    Space radiation risk to astronauts and electronic equipments is one major obstacle in long term human space explorations. Space radiation transport codes have been developed to calculate radiation effects behind materials in human missions to the Moon, Mars or beyond. We study how nuclear fragmentation processes affect the accuracy of predictions from such radiation transport. In particular, we investigate the effects of fragmentation cross sections at different energies on fluxes, dose and dose-equivalent from galactic cosmic rays behind typical shielding materials. These results tell us at what energies nuclear cross sections are the most important for radiation risk evaluations, and how uncertainties in our knowledge about nuclear fragmentations relate to uncertainties in space transport predictions.

  2. COPI-mediated retrograde trafficking from the Golgi to the ER regulates EGFR nuclear transport

    SciTech Connect

    Wang, Ying-Nai; Wang, Hongmei; Yamaguchi, Hirohito; Lee, Hong-Jen; Lee, Heng-Huan; Hung, Mien-Chie

    2010-09-03

    Research highlights: {yields} ARF1 activation is involved in the EGFR transport to the ER and the nucleus. {yields} Assembly of {gamma}-COP coatomer mediates EGFR transport to the ER and the nucleus. {yields} Golgi-to-ER retrograde trafficking regulates nuclear transport of EGFR. -- Abstract: Emerging evidence indicates that cell surface receptors, such as the entire epidermal growth factor receptor (EGFR) family, have been shown to localize in the nucleus. A retrograde route from the Golgi to the endoplasmic reticulum (ER) is postulated to be involved in the EGFR trafficking to the nucleus; however, the molecular mechanism in this proposed model remains unexplored. Here, we demonstrate that membrane-embedded vesicular trafficking is involved in the nuclear transport of EGFR. Confocal immunofluorescence reveals that in response to EGF, a portion of EGFR redistributes to the Golgi and the ER, where its NH{sub 2}-terminus resides within the lumen of Golgi/ER and COOH-terminus is exposed to the cytoplasm. Blockage of the Golgi-to-ER retrograde trafficking by brefeldin A or dominant mutants of the small GTPase ADP-ribosylation factor, which both resulted in the disassembly of the coat protein complex I (COPI) coat to the Golgi, inhibit EGFR transport to the ER and the nucleus. We further find that EGF-dependent nuclear transport of EGFR is regulated by retrograde trafficking from the Golgi to the ER involving an association of EGFR with {gamma}-COP, one of the subunits of the COPI coatomer. Our findings experimentally provide a comprehensive pathway that nuclear transport of EGFR is regulated by COPI-mediated vesicular trafficking from the Golgi to the ER, and may serve as a general mechanism in regulating the nuclear transport of other cell surface receptors.

  3. Global enhancement of nuclear localization-dependent nuclear transport in transformed cells.

    PubMed

    Kuusisto, Henna V; Wagstaff, Kylie M; Alvisi, Gualtiero; Roth, Daniela M; Jans, David A

    2012-03-01

    Fundamental to eukaryotic cell function, nucleocytoplasmic transport can be regulated at many levels, including through modulation of the importin/exportin (Imp/Exp) nuclear transport machinery itself. Although Imps/Exps are overexpressed in a number of transformed cell lines and patient tumor tissues, the efficiency of nucleocytoplasmic transport in transformed cell types compared with nontransformed cells has not been investigated. Here we use quantitative live cell imaging of 3 isogenic nontransformed/transformed cell pairs to show that nuclear accumulation of nuclear localization signal (NLS)-containing proteins, but not their NLS-mutated derivatives, is increased up to 7-fold in MCF10CA1h human epithelial breast carcinoma cells and in simian virus 40 (SV40)-transformed fibroblasts of human and monkey origin, compared with their nontransformed counterparts. The basis for this appears to be a significantly faster rate of nuclear import in transformed cell types, as revealed by analysis using fluorescence recovery after photobleaching for the human MCF10A/MCF10CA1h cell pair. Nuclear accumulation of NLS/nuclear export signal-containing (shuttling) proteins was also enhanced in transformed cell types, experiments using the nuclear export inhibitor leptomycin B demonstrating that efficient Exp-1-mediated nuclear export was not impaired in transformed compared with nontransformed cells. Enhanced nuclear import and export efficiencies were found to correlate with 2- to 4-fold higher expression of specific Imps/Exps in transformed cells, as indicated by quantitative Western blot analysis, with ectopic expression of Imps able to enhance NLS nuclear accumulation levels up to 5-fold in nontransformed MCF10A cells. The findings indicate that transformed cells possess altered nuclear transport properties, most likely due to the overexpression of Imps/Exps. The findings have important implications for the development of tumor-specific drug nanocarriers in anticancer therapy.

  4. Vulnerability Analysis Considerations for the Transportation of Special Nuclear Material

    SciTech Connect

    Nicholson, Lary G.; Purvis, James W.

    1999-07-21

    The vulnerability analysis methodology developed for fixed nuclear material sites has proven to be extremely effective in assessing associated transportation issues. The basic methods and techniques used are directly applicable to conducting a transportation vulnerability analysis. The purpose of this paper is to illustrate that the same physical protection elements (detection, delay, and response) are present, although the response force plays a dominant role in preventing the theft or sabotage of material. Transportation systems are continuously exposed to the general public whereas the fixed site location by its very nature restricts general public access.

  5. Charge transport in disordered semiconducting polymers driven by nuclear tunneling

    NASA Astrophysics Data System (ADS)

    van der Kaap, N. J.; Katsouras, I.; Asadi, K.; Blom, P. W. M.; Koster, L. J. A.; de Leeuw, D. M.

    2016-04-01

    The current density-voltage (J -V ) characteristics of hole-only diodes based on poly(2-methoxy, 5-(2' ethyl-hexyloxy)-p -phenylene vinylene) (MEH-PPV) were measured at a wide temperature and field range. At high electric fields the temperature dependence of the transport vanishes, and all J -V sweeps converge to a power law. Nuclear tunneling theory predicts a power law at high fields that scales with the Kondo parameter. To model the J -V characteristics we have performed master-equation calculations to determine the dependence of charge carrier mobility on electric field, charge carrier density, temperature, and Kondo parameter, using nuclear tunneling transfer rates. We demonstrate that nuclear tunneling, unlike other semiclassical models, provides a consistent description of the charge transport for a large bias, temperature, and carrier density range.

  6. Artificial nanopores that mimic the transport selectivity of the nuclear pore complex

    PubMed Central

    Jovanovic-Talisman, Tijana; Tetenbaum-Novatt, Jaclyn; McKenney, Anna Sophia; Zilman, Anton; Peters, Reiner; Rout, Michael P.; Chait, Brian T.

    2009-01-01

    Nuclear pore complexes (NPCs) act as effective and robust gateways between the nucleus and the cytoplasm, selecting for the passage of particular macromolecules across the nuclear envelope. NPCs are comprised of an elaborate scaffold that defines a ∼30nm diameter passageway connecting the nucleus and the cytoplasm. This scaffold anchors proteins termed ‘phenylalanine-glycine’ (FG)-nucleoporins, the natively disordered domains of which line the passageway and extend into its lumen1. Passive diffusion through this lined passageway is hindered in a size-dependent manner. However, transport factors and their cargo-bound complexes overcome this restriction by transient binding to the FG-nucleoporins2–10. To test whether a simple passageway and a lining of transport-factor-binding FG-nucleoporins are sufficient for selective transport, we designed a functionalized membrane that incorporates just these two elements. Here we demonstrate that this membrane functions as a nanoselective filter, efficiently passing transport factors and transport-factor–cargo complexes that specifically bind FG-nucleoporins, while significantly inhibiting the passage of proteins that do not. This inhibition is greatly enhanced when transport factor is present. Determinants of selectivity include the passageway diameter, the length of the nanopore region coated with FG-nucleoporins, the binding strength to FG-nucleoporins, and the antagonistic effect of transport factors on the passage of proteins that do not specifically bind FG-nucleoporins. We show that this artificial system faithfully reproduces key features of trafficking through the NPC, including transport-factor-mediated cargo import. PMID:19098896

  7. Neutron transport analysis for nuclear reactor design

    DOEpatents

    Vujic, Jasmina L.

    1993-01-01

    Replacing regular mesh-dependent ray tracing modules in a collision/transfer probability (CTP) code with a ray tracing module based upon combinatorial geometry of a modified geometrical module (GMC) provides a general geometry transfer theory code in two dimensions (2D) for analyzing nuclear reactor design and control. The primary modification of the GMC module involves generation of a fixed inner frame and a rotating outer frame, where the inner frame contains all reactor regions of interest, e.g., part of a reactor assembly, an assembly, or several assemblies, and the outer frame, with a set of parallel equidistant rays (lines) attached to it, rotates around the inner frame. The modified GMC module allows for determining for each parallel ray (line), the intersections with zone boundaries, the path length between the intersections, the total number of zones on a track, the zone and medium numbers, and the intersections with the outer surface, which parameters may be used in the CTP code to calculate collision/transfer probability and cross-section values.

  8. Neutron transport analysis for nuclear reactor design

    DOEpatents

    Vujic, J.L.

    1993-11-30

    Replacing regular mesh-dependent ray tracing modules in a collision/transfer probability (CTP) code with a ray tracing module based upon combinatorial geometry of a modified geometrical module (GMC) provides a general geometry transfer theory code in two dimensions (2D) for analyzing nuclear reactor design and control. The primary modification of the GMC module involves generation of a fixed inner frame and a rotating outer frame, where the inner frame contains all reactor regions of interest, e.g., part of a reactor assembly, an assembly, or several assemblies, and the outer frame, with a set of parallel equidistant rays (lines) attached to it, rotates around the inner frame. The modified GMC module allows for determining for each parallel ray (line), the intersections with zone boundaries, the path length between the intersections, the total number of zones on a track, the zone and medium numbers, and the intersections with the outer surface, which parameters may be used in the CTP code to calculate collision/transfer probability and cross-section values. 28 figures.

  9. Organizational factors and nuclear power plant safety

    SciTech Connect

    Haber, S.B.

    1995-12-31

    There are many organizations in our society that depend on human performance to avoid incidents involving significant adverse consequences. As our culture and technology have become more sophisticated, the management of risk on a broad basis has become more and more critical. The safe operation of military facilities, chemical plants, airlines, and mass transit, to name a few, are substantially dependent on the performance of the organizations that operate those facilities. The nuclear power industry has, within the past 15 years, increased the attention given to the influence of human performance in the safe operation of nuclear power plants (NPP). While NPPs have been designed through engineering disciplines to intercept and mitigate events that could cause adverse consequences, it has been clear from various safety-related incidents that human performance also plays a dominant role in preventing accidents. Initial efforts following the 1979 Three Mile Island incident focused primarily on ergonomic factors (e.g., the best design of control rooms for maximum performance). Greater attention was subsequently directed towards cognitive processes involved in the use of NPP decision support systems and decision making in general, personnel functions such as selection systems, and the influence of work scheduling and planning on employees` performance. Although each of these approaches has contributed to increasing the safety of NPPS, during the last few years, there has been a growing awareness that particular attention must be paid to how organizational processes affect NPP personnel performance, and thus, plant safety. The direct importance of organizational factors on safety performance in the NPP has been well-documented in the reports on the Three Mile Island and Chernobyl accidents as well as numerous other events, especially as evaluated by the U.S. Nuclear Regulatory Commission (NRC).

  10. Retinoblastoma-binding Protein 4-regulated Classical Nuclear Transport Is Involved in Cellular Senescence.

    PubMed

    Tsujii, Akira; Miyamoto, Yoichi; Moriyama, Tetsuji; Tsuchiya, Yuko; Obuse, Chikashi; Mizuguchi, Kenji; Oka, Masahiro; Yoneda, Yoshihiro

    2015-12-01

    Nucleocytoplasmic trafficking is a fundamental cellular process in eukaryotic cells. Here, we demonstrated that retinoblastoma-binding protein 4 (RBBP4) functions as a novel regulatory factor to increase the efficiency of importin α/β-mediated nuclear import. RBBP4 accelerates the release of importin β1 from importin α via competitive binding to the importin β-binding domain of importin α in the presence of RanGTP. Therefore, it facilitates importin α/β-mediated nuclear import. We showed that the importin α/β pathway is down-regulated in replicative senescent cells, concomitant with a decrease in RBBP4 level. Knockdown of RBBP4 caused both suppression of nuclear transport and induction of cellular senescence. This is the first report to identify a factor that competes with importin β1 to bind to importin α, and it demonstrates that the loss of this factor can trigger cellular senescence.

  11. Spent Nuclear Fuel Transportation Risk Assessment Methodology for Homeland Security

    SciTech Connect

    Teagarden, Grant A.; Canavan, Kenneth T.; Nickell, Robert E.

    2006-07-01

    In response to increased interest in risk-informed decision making regarding terrorism, EPRI was selected by U.S. DHS and ASME to develop and demonstrate a nuclear sector specific methodology for owner / operators to utilize in performing a Risk Analysis and Management for Critical Asset Protection (RAMCAP) assessment for the transportation of spent nuclear fuel (SNF). The objective is to characterize SNF transportation risk for risk management opportunities and to provide consistent information for DHS decision making. The method uses a characterization of risk as a function of Consequence, Vulnerability, and Threat. Worst reasonable case scenarios characterize risk for a benchmark set of threats and consequence types. A trial application was successfully performed and implementation is underway by one utility. (authors)

  12. Non-nuclear Electron Transport Channels in Hollow Molecules

    SciTech Connect

    Zhao, Jin; Petek, Hrvoje

    2014-08-15

    Electron transport in inorganic semiconductors and metals occurs through delocalized bands formed by overlapping electron orbitals. Strong correlation of electronic wave functions with the ionic cores couples the electron and lattice motions, leading to efficient interaction and scattering that degrades coherent charge transport. By contrast, unoccupied electronic states at energies near the vacuum level with diffuse molecular orbitals may form nearly-free-electron bands with density maxima in non-nuclear interstitial voids, which are subject to weaker electron-phonon interaction. The position of such bands typically above the frontier orbitals, however, renders them unstable with respect to electronic interband relaxation and therefore unsuitable for charge transport. Through electronic-structure calculations, we engineer stable, non-nuclear, nearly-free-electron conduction channels in low-dimensional molecular materials by tailoring their electrostatic and polarization potentials. We propose quantum structures of graphane-derived Janus molecular sheets with spatially isolated conducting and insulating regions that potentially exhibit emergent electronic properties, as a paradigm for molecular-scale non-nuclear charge conductors; we also describe tuning of their electronic properties by application of external fields and calculate their electron–acoustic-phonon interaction.

  13. Non-nuclear electron transport channels in hollow molecules

    NASA Astrophysics Data System (ADS)

    Zhao, Jin; Petek, Hrvoje

    2014-08-01

    Electron transport in inorganic semiconductors and metals occurs through delocalized bands formed by overlapping electron orbitals. Strong correlation of electronic wave functions with the ionic cores couples the electron and lattice motions, leading to efficient interaction and scattering that degrades coherent charge transport. By contrast, unoccupied electronic states at energies near the vacuum level with diffuse molecular orbitals may form nearly-free-electron bands with density maxima in non-nuclear interstitial voids, which are subject to weaker electron-phonon interaction. The position of such bands typically above the frontier orbitals, however, renders them unstable with respect to electronic interband relaxation and therefore unsuitable for charge transport. Through electronic-structure calculations, we engineer stable, non-nuclear, nearly-free-electron conduction channels in low-dimensional molecular materials by tailoring their electrostatic and polarization potentials. We propose quantum structures of graphane-derived Janus molecular sheets with spatially isolated conducting and insulating regions that potentially exhibit emergent electronic properties, as a paradigm for molecular-scale non-nuclear charge conductors; we also describe tuning of their electronic properties by application of external fields and calculate their electron-acoustic-phonon interaction.

  14. A Transport Model for Nuclear Reactions Induced by Radioactive Beams

    SciTech Connect

    Li Baoan; Chen Liewen; Das, Champak B.; Das Gupta, Subal; Gale, Charles; Ko, C.M.; Yong, G.-C.; Zuo Wei

    2005-10-14

    Major ingredients of an isospin and momentum dependent transport model for nuclear reactions induced by radioactive beams are outlined. Within the IBUU04 version of this model we study several experimental probes of the equation of state of neutron-rich matter, especially the density dependence of the nuclear symmetry energy. Comparing with the recent experimental data from NSCL/MSU on isospin diffusion, we found a nuclear symmetry energy of Esym({rho}) {approx_equal} 31.6({rho}/{rho}0)1.05 at subnormal densities. Predictions on several observables sensitive to the density dependence of the symmetry energy at supranormal densities accessible at GSI and the planned Rare Isotope Accelerator (RIA) are also made.

  15. Isotopic Effects in Nuclear Fragmentation and GCR Transport Problems

    NASA Technical Reports Server (NTRS)

    Cucinotta, Francis A.

    2002-01-01

    Improving the accuracy of the galactic cosmic ray (GCR) environment and transport models is an important goal in preparing for studies of the projected risks and the efficiency of potential mitigations methods for space exploration. In this paper we consider the effects of the isotopic composition of the primary cosmic rays and the isotopic dependence of nuclear fragmentation cross sections on GCR transport models. Measurements are used to describe the isotopic composition of the GCR including their modulation throughout the solar cycle. The quantum multiple-scattering approach to nuclear fragmentation (QMSFRG) is used as the data base generator in order to accurately describe the odd-even effect in fragment production. Using the Badhwar and O'Neill GCR model, the QMSFRG model and the HZETRN transport code, the effects of the isotopic dependence of the primary GCR composition and on fragment production for transport problems is described for a complete GCR isotopic-grid. The principle finding of this study is that large errors ( 100%) will occur in the mass-flux spectra when comparing the complete isotopic-grid (141 ions) to a reduced isotopic-grid (59 ions), however less significant errors 30%) occur in the elemental-flux spectra. Because the full isotopic-grid is readily handled on small computer work-stations, it is recommended that they be used for future GCR studies.

  16. The Storage, Transportation, and Disposal of Nuclear Waste

    NASA Astrophysics Data System (ADS)

    Younker, J. L.

    2002-12-01

    The U.S. Congress established a comprehensive federal policy to dispose of wastes from nuclear reactors and defense facilities, centered on deep geologic disposal of high-level radioactive waste. Site screening led to selection of three potential sites and in 1987, Congress directed the Secretary of Energy to characterize only one site: Yucca Mountain in Nevada. For more than 20 years, teams of scientists and engineers have been evaluating the potential suitability of the site. On the basis of their work, the U.S. Secretary of Energy, Spencer Abraham, concluded in February 2002 that a safe repository can be sited at Yucca Mountain. On July 23, 2002, President Bush signed Joint Resolution 87 approving the site at Yucca Mountain for development of a repository, which allows the U.S. Department of Energy (DOE) to prepare and submit a license application to the U.S. Nuclear Regulatory Commission (NRC). Concerns have been raised relative to the safe transportation of nuclear materials. The U.S. history of transportation of nuclear materials demonstrates that high-level nuclear materials can be safely transported. Since the 1960s, over 1.6 million miles have been traveled by more than 2,700 spent nuclear fuel shipments, and there has never been an accident severe enough to cause a release of radioactive materials. The DOE will use NRC-certified casks that must be able to withstand very stringent tests. The same design features that allow the casks to survive severe accidents also limit their vulnerability to sabotage. In addition, the NRC will approve all shipping routes and security plans. With regard to long-term safety, the Yucca Mountain disposal system has five key attributes. First, the arid climate and geology of Yucca Mountain combine to ensure that limited water will enter the emplacement tunnels. Second, the DOE has designed a waste package and drip shield that are expected to have very long lifetimes in the repository environment. Third, waste form

  17. [Intracellular transport of nuclear ribosomal RNA in Acetabularia mediterranea].

    PubMed

    Naumova, L P; Pressman, E K; Sandakhchiev, L S

    1976-01-01

    The ribosomal RNA transport from a nucleus to a perinuclear cytoplasm and its following distribution in the cytoplasm of Acetabularia mediterranea cells were studied using transplantation of RNA-labeled rhizoid into unlabeled stalk. In addition rifamycin treatment was used for inhibition of cytoplasmic RNA synthesis. Acetabularia nuclei contain the stable RNA fractions similar to those present in some other eukaryotes. Nuclear 25S and 17S ribosomal RNA rapidly enter the rhizoid cytoplasm whereas the following trasfer of them to other regions of the cell is a very slow process. Within two days only an insignificant part of 25S and 17S ribosomal RNA is transferred from the rhizoid to the stalk and is distributed there over the base-apical gradient. No preferential transfer of the nuclear ribosomal RNA to the apical region was observed.

  18. SRSF1 regulates the assembly of pre-mRNA processing factors in nuclear speckles.

    PubMed

    Tripathi, Vidisha; Song, David Y; Zong, Xinying; Shevtsov, Sergey P; Hearn, Stephen; Fu, Xiang-Dong; Dundr, Miroslav; Prasanth, Kannanganattu V

    2012-09-01

    The mammalian cell nucleus is compartmentalized into nonmembranous subnuclear domains that regulate key nuclear functions. Nuclear speckles are subnuclear domains that contain pre-mRNA processing factors and noncoding RNAs. Many of the nuclear speckle constituents work in concert to coordinate multiple steps of gene expression, including transcription, pre-mRNA processing and mRNA transport. The mechanism that regulates the formation and maintenance of nuclear speckles in the interphase nucleus is poorly understood. In the present study, we provide evidence for the involvement of nuclear speckle resident proteins and RNA components in the organization of nuclear speckles. SR-family splicing factors and their binding partner, long noncoding metastasis-associated lung adenocarcinoma transcript 1 RNA, can nucleate the assembly of nuclear speckles in the interphase nucleus. Depletion of SRSF1 in human cells compromises the association of splicing factors to nuclear speckles and influences the levels and activity of other SR proteins. Furthermore, on a stably integrated reporter gene locus, we demonstrate the role of SRSF1 in RNA polymerase II-mediated transcription. Our results suggest that SR proteins mediate the assembly of nuclear speckles and regulate gene expression by influencing both transcriptional and posttranscriptional activities within the cell nucleus.

  19. Public opinion factors regarding nuclear power

    SciTech Connect

    Benson, B.

    1991-12-31

    This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry`s practices are aligned with public opinion, a more favorable regulatory climate is possible.

  20. Public opinion factors regarding nuclear power

    SciTech Connect

    Benson, B.

    1991-01-01

    This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry's practices are aligned with public opinion, a more favorable regulatory climate is possible.

  1. 75 FR 38151 - Governors' Designees Receiving Advance Notification of Transportation of Nuclear Waste

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... COMMISSION Governors' Designees Receiving Advance Notification of Transportation of Nuclear Waste On January... prior to transportation of certain shipments of nuclear waste and spent fuel. The advance notification... numbers of those individuals in each State who are responsible for receiving information on nuclear...

  2. 10 CFR 150.21 - Transportation of special nuclear material by aircraft.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Transportation of special nuclear material by aircraft. 150.21 Section 150.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXEMPTIONS AND CONTINUED... Transportation of special nuclear material by aircraft. Except as specifically approved by the Commission...

  3. 10 CFR 150.21 - Transportation of special nuclear material by aircraft.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Transportation of special nuclear material by aircraft. 150.21 Section 150.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXEMPTIONS AND CONTINUED... Transportation of special nuclear material by aircraft. Except as specifically approved by the Commission...

  4. 10 CFR 150.21 - Transportation of special nuclear material by aircraft.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Transportation of special nuclear material by aircraft. 150.21 Section 150.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXEMPTIONS AND CONTINUED... Transportation of special nuclear material by aircraft. Except as specifically approved by the Commission...

  5. 10 CFR 150.21 - Transportation of special nuclear material by aircraft.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Transportation of special nuclear material by aircraft. 150.21 Section 150.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXEMPTIONS AND CONTINUED... Transportation of special nuclear material by aircraft. Except as specifically approved by the Commission...

  6. 10 CFR 150.21 - Transportation of special nuclear material by aircraft.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Transportation of special nuclear material by aircraft. 150.21 Section 150.21 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) EXEMPTIONS AND CONTINUED... Transportation of special nuclear material by aircraft. Except as specifically approved by the Commission...

  7. Slide-and-exchange mechanism for rapid and selective transport through the nuclear pore complex

    PubMed Central

    Raveh, Barak; Karp, Jerome M.; Sparks, Samuel; Rout, Michael P.; Sali, Andrej; Cowburn, David

    2016-01-01

    Nucleocytoplasmic transport is mediated by the interaction of transport factors (TFs) with disordered phenylalanine-glycine (FG) repeats that fill the central channel of the nuclear pore complex (NPC). However, the mechanism by which TFs rapidly diffuse through multiple FG repeats without compromising NPC selectivity is not yet fully understood. In this study, we build on our recent NMR investigations showing that FG repeats are highly dynamic, flexible, and rapidly exchanging among TF interaction sites. We use unbiased long timescale all-atom simulations on the Anton supercomputer, combined with extensive enhanced sampling simulations and NMR experiments, to characterize the thermodynamic and kinetic properties of FG repeats and their interaction with a model transport factor. Both the simulations and experimental data indicate that FG repeats are highly dynamic random coils, lack intrachain interactions, and exhibit significant entropically driven resistance to spatial confinement. We show that the FG motifs reversibly slide in and out of multiple TF interaction sites, transitioning rapidly between a strongly interacting state and a weakly interacting state, rather than undergoing a much slower transition between strongly interacting and completely noninteracting (unbound) states. In the weakly interacting state, FG motifs can be more easily displaced by other competing FG motifs, providing a simple mechanism for rapid exchange of TF/FG motif contacts during transport. This slide-and-exchange mechanism highlights the direct role of the disorder within FG repeats in nucleocytoplasmic transport, and resolves the apparent conflict between the selectivity and speed of transport. PMID:27091992

  8. Slide-and-exchange mechanism for rapid and selective transport through the nuclear pore complex.

    PubMed

    Raveh, Barak; Karp, Jerome M; Sparks, Samuel; Dutta, Kaushik; Rout, Michael P; Sali, Andrej; Cowburn, David

    2016-05-01

    Nucleocytoplasmic transport is mediated by the interaction of transport factors (TFs) with disordered phenylalanine-glycine (FG) repeats that fill the central channel of the nuclear pore complex (NPC). However, the mechanism by which TFs rapidly diffuse through multiple FG repeats without compromising NPC selectivity is not yet fully understood. In this study, we build on our recent NMR investigations showing that FG repeats are highly dynamic, flexible, and rapidly exchanging among TF interaction sites. We use unbiased long timescale all-atom simulations on the Anton supercomputer, combined with extensive enhanced sampling simulations and NMR experiments, to characterize the thermodynamic and kinetic properties of FG repeats and their interaction with a model transport factor. Both the simulations and experimental data indicate that FG repeats are highly dynamic random coils, lack intrachain interactions, and exhibit significant entropically driven resistance to spatial confinement. We show that the FG motifs reversibly slide in and out of multiple TF interaction sites, transitioning rapidly between a strongly interacting state and a weakly interacting state, rather than undergoing a much slower transition between strongly interacting and completely noninteracting (unbound) states. In the weakly interacting state, FG motifs can be more easily displaced by other competing FG motifs, providing a simple mechanism for rapid exchange of TF/FG motif contacts during transport. This slide-and-exchange mechanism highlights the direct role of the disorder within FG repeats in nucleocytoplasmic transport, and resolves the apparent conflict between the selectivity and speed of transport. PMID:27091992

  9. 25 CFR 170.900 - What is the purpose of the provisions relating to transportation of hazardous and nuclear waste?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... transportation of hazardous and nuclear waste? 170.900 Section 170.900 Indians BUREAU OF INDIAN AFFAIRS... and Nuclear Waste Transportation § 170.900 What is the purpose of the provisions relating to transportation of hazardous and nuclear waste? Sections 170.900 through 170.907 on transportation of nuclear...

  10. 25 CFR 170.900 - What is the purpose of the provisions relating to transportation of hazardous and nuclear waste?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... transportation of hazardous and nuclear waste? 170.900 Section 170.900 Indians BUREAU OF INDIAN AFFAIRS... and Nuclear Waste Transportation § 170.900 What is the purpose of the provisions relating to transportation of hazardous and nuclear waste? Sections 170.900 through 170.907 on transportation of nuclear...

  11. 25 CFR 170.900 - What is the purpose of the provisions relating to transportation of hazardous and nuclear waste?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... transportation of hazardous and nuclear waste? 170.900 Section 170.900 Indians BUREAU OF INDIAN AFFAIRS... and Nuclear Waste Transportation § 170.900 What is the purpose of the provisions relating to transportation of hazardous and nuclear waste? Sections 170.900 through 170.907 on transportation of nuclear...

  12. 25 CFR 170.900 - What is the purpose of the provisions relating to transportation of hazardous and nuclear waste?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... transportation of hazardous and nuclear waste? 170.900 Section 170.900 Indians BUREAU OF INDIAN AFFAIRS... and Nuclear Waste Transportation § 170.900 What is the purpose of the provisions relating to transportation of hazardous and nuclear waste? Sections 170.900 through 170.907 on transportation of nuclear...

  13. 25 CFR 170.900 - What is the purpose of the provisions relating to transportation of hazardous and nuclear waste?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... transportation of hazardous and nuclear waste? 170.900 Section 170.900 Indians BUREAU OF INDIAN AFFAIRS... and Nuclear Waste Transportation § 170.900 What is the purpose of the provisions relating to transportation of hazardous and nuclear waste? Sections 170.900 through 170.907 on transportation of nuclear...

  14. Variance Reduction Factor of Nuclear Data for Integral Neutronics Parameters

    SciTech Connect

    Chiba, G. Tsuji, M.; Narabayashi, T.

    2015-01-15

    We propose a new quantity, a variance reduction factor, to identify nuclear data for which further improvements are required to reduce uncertainties of target integral neutronics parameters. Important energy ranges can be also identified with this variance reduction factor. Variance reduction factors are calculated for several integral neutronics parameters. The usefulness of the variance reduction factors is demonstrated.

  15. Transport calculations for nuclear analyses: Theory and guidelines for effective use of transport codes

    SciTech Connect

    O'Dell, R.D.; Alcouffe, R.E.

    1987-09-01

    This report is for the serious user of discrete ordinates transport computer codes for performing nuclear analysis calculations. The first section after the introduction provides a reasonably thorough mathematical description of the analytic Boltzmann transport equation. Next is a section on the numerical discretization of the energy, angle, and space variables in the transport equation, along with an introduction to the source iteration method. The fourth section provides numerical details and features pertinent to discrete ordinates codes. That section details angular quadrature, spatial discretization methods, iteration acceleration methods, and search capabilities. The fifth section presents considerations in choosing a discrete ordinates code for use, and this is followed by a section on typical discrete ordinates codes available throughout the world. The report ends with some guidance for the user. 73 refs., 18 figs., 13 tabs.

  16. Nuclear thermal propulsion transportation systems for lunar/Mars exploration

    NASA Technical Reports Server (NTRS)

    Clark, John S.; Borowski, Stanley K.; Mcilwain, Melvin C.; Pellaccio, Dennis G.

    1992-01-01

    Nuclear thermal propulsion technology development is underway at NASA and DoE for Space Exploration Initiative (SEI) missions to Mars, with initial near-earth flights to validate flight readiness. Several reactor concepts are being considered for these missions, and important selection criteria will be evaluated before final selection of a system. These criteria include: safety and reliability, technical risk, cost, and performance, in that order. Of the concepts evaluated to date, the Nuclear Engine for Rocket Vehicle Applications (NERVA) derivative (NDR) is the only concept that has demonstrated full power, life, and performance in actual reactor tests. Other concepts will require significant design work and must demonstrate proof-of-concept. Technical risk, and hence, development cost should therefore be lowest for the concept, and the NDR concept is currently being considered for the initial SEI missions. As lighter weight, higher performance systems are developed and validated, including appropriate safety and astronaut-rating requirements, they will be considered to support future SEI application. A space transportation system using a modular nuclear thermal rocket (NTR) system for lunar and Mars missions is expected to result in significant life cycle cost savings. Finally, several key issues remain for NTR's, including public acceptance and operational issues. Nonetheless, NTR's are believed to be the 'next generation' of space propulsion systems - the key to space exploration.

  17. RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1

    PubMed Central

    Rajakylä, Eeva Kaisa; Viita, Tiina; Kyheröinen, Salla; Huet, Guillaume; Treisman, Richard; Vartiainen, Maria K.

    2015-01-01

    Controlled transport of macromolecules between the cytoplasm and nucleus is essential for homeostatic regulation of cellular functions. For instance, gene expression entails coordinated nuclear import of transcriptional regulators to activate transcription and nuclear export of the resulting messenger RNAs for cytoplasmic translation. Here we link these two processes by reporting a novel role for the mRNA export factor Ddx19/Dbp5 in nuclear import of MKL1, the signal-responsive transcriptional activator of SRF. We show that Ddx19 is not a general nuclear import factor, and that its specific effect on MKL1 nuclear import is separate from its role in mRNA export. Both helicase and nuclear pore-binding activities of Ddx19 are dispensable for MKL1 nuclear import, but RNA binding is required. Mechanistically, Ddx19 operates by modulating the conformation of MKL1, which affects its interaction with Importin-β for efficient nuclear import. Thus, Ddx19 participates in mRNA export, translation and nuclear import of a key transcriptional regulator. PMID:25585691

  18. 75 FR 53686 - Blue Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-01

    ... spent nuclear fuel and nuclear waste. The Co-chairs of the Commission requested the formation of the T&S... Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee AGENCY: Department of Energy, Office of Nuclear Energy. ACTION: Notice of open meeting. SUMMARY: This notice...

  19. 75 FR 45608 - Blue Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ..., processing, and disposal of civilian and defense spent nuclear fuel and nuclear waste. The Co-chairs of the... the way in which it is storing used nuclear fuel and high level waste while one or more final disposal... Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee AGENCY:...

  20. 75 FR 64720 - Blue Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ... spent nuclear fuel and nuclear waste. The Co-chairs of the Commission requested the formation of the T&S... Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee AGENCY: Office of Nuclear Energy, Department of Energy. ACTION: Notice of Open Meeting. SUMMARY: This notice announces...

  1. The molecular mechanism of nuclear transport revealed by atomic-scale measurements

    PubMed Central

    Hough, Loren E; Dutta, Kaushik; Sparks, Samuel; Temel, Deniz B; Kamal, Alia; Tetenbaum-Novatt, Jaclyn; Rout, Michael P; Cowburn, David

    2015-01-01

    Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC. DOI: http://dx.doi.org/10.7554/eLife.10027.001 PMID:26371551

  2. High-speed civil transport study: Special factors

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Studies relating to environmental factors associated with high speed civil transports were conducted. Projected total engine emissions for year 2015 fleets of several subsonic/supersonic transport fleet scenarios, discussion of sonic boom reduction methods, discussion of community noise level requirements, fuels considerations, and air traffic control impact are presented.

  3. Specific transport and storage solutions : waste management facing current and future stakes of the nuclear fuel cycle

    SciTech Connect

    Choho, T.; Blachet, L.; Deniau, H.; Gagner, L.; Gendreau, F.; Presta, A.

    2007-07-01

    With major projects ongoing or being planned, and also with the daily management of radioactive waste from nuclear facilities, the role of transport and/or storage packaging has been often overlooked. Indeed, the packaging development process and transport solutions implemented are a key part of the waste management challenge : protection of people and of the environment. During over four decades, the AREVA Group has developed a complete and coherent system for the transport of waste produced by nuclear industries. The transport solutions integrate the factors to consider, as industrial transportation needs, various waste forms, associated hazards and current regulations. Thus, TN International has designed, licensed and manufactured a large number of different transport, storage and dual purpose cask models for residues and all kinds of radioactive wastes. The present paper proposes to illustrate how a company acting both as a cask designer and a carrier is key to the waste management issue and how it can support the waste management policy of nuclear waste producers through their operational choices. We will focus on the TN International technical solutions implemented to guarantee safe and secure transportation and storage solutions. We will describe different aspects of the cask design process, insisting on how it enables to fulfil both customer needs and regulation requirements. We will also mention the associated services developed by the AREVA Business Unit Logistics (TN International, TRANSNUCLEAR, MAINCO, and LMC) in order to manage transportation of liquid and solid waste towards interim or final storage sites. (authors)

  4. The Dose Rate Conversion Factors for Nuclear Fallout

    SciTech Connect

    Spriggs, G D

    2009-02-13

    In a previous paper, the composite exposure rate conversion factor (ECF) for nuclear fallout was calculated using a simple theoretical photon-transport model. The theoretical model was used to fill in the gaps in the FGR-12 table generated by ORNL. The FGR-12 table contains the individual conversion factors for approximate 1000 radionuclides. However, in order to calculate the exposure rate during the first 30 minutes following a nuclear detonation, the conversion factors for approximately 2000 radionuclides are needed. From a human-effects standpoint, it is also necessary to have the dose rate conversion factors (DCFs) for all 2000 radionuclides. The DCFs are used to predict the whole-body dose rates that would occur if a human were standing in a radiation field of known exposure rate. As calculated by ORNL, the whole-body dose rate (rem/hr) is approximately 70% of the exposure rate (R/hr) at one meter above the surface. Hence, the individual DCFs could be estimated by multiplying the individual ECFs by 0.7. Although this is a handy rule-of-thumb, a more consistent (and perhaps, more accurate) method of estimating the individual DCFs for the missing radionuclides in the FGR-12 table is to use the linear relationship between DCF and total gamma energy released per decay. This relationship is shown in Figure 1. The DCFs for individual organs in the body can also be estimated from the estimated whole-body DCF. Using the DCFs given FGR-12, the ratio of the organ-specific DCFs to the whole-body DCF were plotted as a function of the whole-body DCF. From these plots, the asymptotic ratios were obtained (see Table 1). Using these asymptotic ratios, the organ-specific DCFs can be estimated using the estimated whole-body DCF for each of the missing radionuclides in the FGR-12 table. Although this procedure for estimating the organ-specific DCFs may over-estimate the value for some low gamma-energy emitters, having a finite value for the organ-specific DCFs in the table is

  5. Human factors aspects of advanced instrumentation in the nuclear industry

    SciTech Connect

    Carter, R.J.

    1989-01-01

    An important consideration in regards to the use of advanced instrumentation in the nuclear industry is the interface between the instrumentation system and the human. A survey, oriented towards identifying the human factors aspects of digital instrumentation, was conducted at a number of United States (US) and Canadian nuclear vendors and utilities. Human factors issues, subsumed under the categories of computer-generated displays, controls, organizational support, training, and related topics were identified. 20 refs., 2 tabs.

  6. Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks.

    PubMed

    Jordan, Amy B; Stauffer, Philip H; Knight, Earl E; Rougier, Esteban; Anderson, Dale N

    2015-01-01

    Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable. PMID:26676058

  7. Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks

    PubMed Central

    Jordan, Amy B.; Stauffer, Philip H.; Knight, Earl E.; Rougier, Esteban; Anderson, Dale N.

    2015-01-01

    Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable. PMID:26676058

  8. Radionuclide gas transport through nuclear explosion-generated fracture networks

    DOE PAGES

    Jordan, Amy B.; Stauffer, Philip H.; Knight, Earl E.; Rougier, Esteban; Anderson, Dale N.

    2015-12-17

    Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gasmore » breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. In conclusion, seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable.« less

  9. Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks.

    PubMed

    Jordan, Amy B; Stauffer, Philip H; Knight, Earl E; Rougier, Esteban; Anderson, Dale N

    2015-12-17

    Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable.

  10. Radionuclide Gas Transport through Nuclear Explosion-Generated Fracture Networks

    NASA Astrophysics Data System (ADS)

    Jordan, Amy B.; Stauffer, Philip H.; Knight, Earl E.; Rougier, Esteban; Anderson, Dale N.

    2015-12-01

    Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. Seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable.

  11. Radionuclide gas transport through nuclear explosion-generated fracture networks

    SciTech Connect

    Jordan, Amy B.; Stauffer, Philip H.; Knight, Earl E.; Rougier, Esteban; Anderson, Dale N.

    2015-12-17

    Underground nuclear weapon testing produces radionuclide gases which may seep to the surface. Barometric pumping of gas through explosion-fractured rock is investigated using a new sequentially-coupled hydrodynamic rock damage/gas transport model. Fracture networks are produced for two rock types (granite and tuff) and three depths of burial. The fracture networks are integrated into a flow and transport numerical model driven by surface pressure signals of differing amplitude and variability. There are major differences between predictions using a realistic fracture network and prior results that used a simplified geometry. Matrix porosity and maximum fracture aperture have the greatest impact on gas breakthrough time and window of opportunity for detection, with different effects between granite and tuff simulations highlighting the importance of accurately simulating the fracture network. In particular, maximum fracture aperture has an opposite effect on tuff and granite, due to different damage patterns and their effect on the barometric pumping process. From stochastic simulations using randomly generated hydrogeologic parameters, normalized detection curves are presented to show differences in optimal sampling time for granite and tuff simulations. In conclusion, seasonal and location-based effects on breakthrough, which occur due to differences in barometric forcing, are stronger where the barometric signal is highly variable.

  12. Evidence for an inhibitory feedback loop regulating simian virus 40 large T-antigen fusion protein nuclear transport.

    PubMed Central

    Seydel, U; Jans, D A

    1996-01-01

    Nuclear protein import is central to eukaryotic cell function. It is dependent on ATP, temperature and cytosolic factors, and requires specific targeting sequences called nuclear localization signals (NLSs). Nuclear import kinetics was studied in vitro using digitonin-permeabilized cells of the HTC rat hepatoma cell line and a fluorescently labelled beta-galactosidase fusion protein carrying amino acids 111-135 of the simian virus 40 large T-antigen (T-ag), including the NLS. Nuclear accumulation was rapid, reaching steady-state after about 80 min at 37 degrees C (t1/2 at about 17 min). Surprisingly, maximal nuclear concentration was found to be directly proportional to the concentration of the cytosolic extract and of cytoplasmic T-ag protein. Neither preincubation of cells for 1 h at 37 degrees C before the addition of T-ag protein nor the addition of fresh transport medium after 1 h and continuation of the incubation for another hour affected the maximal nuclear concentration. If cells were allowed to accumulate T-ag protein for 1 h before the addition of fresh transport medium containing different concentrations of T-ag protein and incubated for a further hour, the maximal nuclear concentration did not change unless the concentration of T-ag protein in the second transport mixture exceeded that in the first, in which case the nuclear concentration increased. Nuclear import of T-ag thus appeared (i) to be strictly unidirectional over 2 h at 37 degrees C and (ii) to be regulated by an inhibitory feedback loop, whereby the cytosolic concentration of protein appears to determine directly the precise end point of nuclear accumulation. This study represents the first characterization of this previously undescribed mechanism of regulation of nuclear protein import. PMID:8670127

  13. The "genomic storm" induced by bacterial endotoxin is calmed by a nuclear transport modifier that attenuates localized and systemic inflammation.

    PubMed

    DiGiandomenico, Antonio; Veach, Ruth Ann; Zienkiewicz, Jozef; Moore, Daniel J; Wylezinski, Lukasz S; Hutchens, Martha A; Hawiger, Jacek

    2014-01-01

    Lipopolysaccharide (LPS) is a potent microbial virulence factor that can trigger production of proinflammatory mediators involved in the pathogenesis of localized and systemic inflammation. Importantly, the role of nuclear transport of stress responsive transcription factors in this LPS-generated "genomic storm" remains largely undefined. We developed a new nuclear transport modifier (NTM) peptide, cell-penetrating cSN50.1, which targets nuclear transport shuttles importin α5 and importin β1, to analyze its effect in LPS-induced localized (acute lung injury) and systemic (lethal endotoxic shock) murine inflammation models. We analyzed a human genome database to match 46 genes that encode cytokines, chemokines and their receptors with transcription factors whose nuclear transport is known to be modulated by NTM. We then tested the effect of cSN50.1 peptide on proinflammatory gene expression in murine bone marrow-derived macrophages stimulated with LPS. This NTM suppressed a proinflammatory transcriptome of 37 out of 84 genes analyzed, without altering expression of housekeeping genes or being cytotoxic. Consistent with gene expression analysis in primary macrophages, plasma levels of 23 out of 26 LPS-induced proinflammatory cytokines, chemokines, and growth factors were significantly attenuated in a murine model of LPS-induced systemic inflammation (lethal endotoxic shock) while the anti-inflammatory cytokine, interleukin 10, was enhanced. This anti-inflammatory reprogramming of the endotoxin-induced genomic response was accompanied by complete protection against lethal endotoxic shock with prophylactic NTM treatment, and 75% protection when NTM was first administered after LPS exposure. In a murine model of localized lung inflammation caused by direct airway exposure to LPS, expression of cytokines and chemokines in the bronchoalveolar space was suppressed with a concomitant reduction of neutrophil trafficking. Thus, calming the LPS-triggered "genomic storm" by

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

    SciTech Connect

    Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim

    2014-07-18

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

  15. 78 FR 35746 - Advance Notification to Native American Tribes of Transportation of Certain Shipments of Nuclear...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... Transportation of Certain Shipments of Nuclear Waste AGENCY: Nuclear Regulatory Commission. ACTION: Final rule... shipments of irradiated reactor fuel and nuclear waste to State Governors or their designees. On June 11...-415- 6628; email: James.Firth@nrc.gov . SUPPLEMENTARY INFORMATION: On January 6, 1982 (47 FR 596...

  16. Factors controlling large-wood transport in a mountain river

    NASA Astrophysics Data System (ADS)

    Ruiz-Villanueva, Virginia; Wyżga, Bartłomiej; Zawiejska, Joanna; Hajdukiewicz, Maciej; Stoffel, Markus

    2016-11-01

    As with bedload transport, wood transport in rivers is governed by several factors such as flow regime, geomorphic configuration of the channel and floodplain, or wood size and shape. Because large-wood tends to be transported during floods, safety and logistical constraints make field measurements difficult. As a result, direct observation and measurements of the conditions of wood transport are scarce. This lack of direct observations and the complexity of the processes involved in wood transport may result in an incomplete understanding of wood transport processes. Numerical modelling provides an alternative approach to addressing some of the unknowns in the dynamics of large-wood in rivers. The aim of this study is to improve the understanding of controls governing wood transport in mountain rivers, combining numerical modelling and direct field observations. By defining different scenarios, we illustrate relationships between the rate of wood transport and discharge, wood size, and river morphology. We test these relationships for a wide, multithread reach and a narrower, partially channelized single-thread reach of the Czarny Dunajec River in the Polish Carpathians. Results indicate that a wide range of quantitative information about wood transport can be obtained from a combination of numerical modelling and field observations and from document contrasting patterns of wood transport in single- and multithread river reaches. On the one hand, log diameter seems to have a greater importance for wood transport in the multithread channel because of shallower flow, lower flow velocity, and lower stream power. Hydrodynamic conditions in the single-thread channel allow transport of large-wood pieces, whereas in the multithread reach, logs with diameters similar to water depth are not being moved. On the other hand, log length also exerts strong control on wood transport, more so in the single-thread than in the multithread reach. In any case, wood transport strongly

  17. Optical recording of signal-mediated protein transport through single nuclear pore complexes.

    PubMed

    Keminer, O; Siebrasse, J P; Zerf, K; Peters, R

    1999-10-12

    Optical single-transporter recording, a recently established fluorescence microscopic method, was used to study the selective transport of proteins through single nuclear pore complexes (NPCs) of Xenopus oocytes. Recombinant proteins containing either a nuclear localization signal (import protein) or a nuclear export signal (export protein) were generated as transport substrates. To approximate in vivo conditions as closely as possible, a Xenopus egg extract was applied to the cytosolic side and a Xenopus oocyte nuclear extract to the nuclear side of the NPCs. It was found that protein transport through functionally isolated, "patched" NPCs depended on signal sequences, extracts, and metabolic energy, as in vivo. All NPCs were competent for both import and export. The transport direction was strictly determined by the transport signal, and at none of the conditions explored was the import protein exported or the export protein imported, even when the application sides of the extracts were reversed. The mean transport rates of the single NPC were approximately 2 dimers/s for the import protein and approximately 4 dimers/s for the export protein ( approximately 15 microM substrate concentration, 22-24 degrees C), in good agreement with in vivo rates estimated for mammalian cells by microinjection experiments. The study shows that optical single-transporter recording permits the analysis of membrane transport processes not previously accessible to single-transporter recording and thus provides additional possibilities for the elucidation of nucleocytoplasmic transport mechanisms. PMID:10518538

  18. Optical recording of signal-mediated protein transport through single nuclear pore complexes

    PubMed Central

    Keminer, Oliver; Siebrasse, Jan-Peter; Zerf, Katja; Peters, Reiner

    1999-01-01

    Optical single-transporter recording, a recently established fluorescence microscopic method, was used to study the selective transport of proteins through single nuclear pore complexes (NPCs) of Xenopus oocytes. Recombinant proteins containing either a nuclear localization signal (import protein) or a nuclear export signal (export protein) were generated as transport substrates. To approximate in vivo conditions as closely as possible, a Xenopus egg extract was applied to the cytosolic side and a Xenopus oocyte nuclear extract to the nuclear side of the NPCs. It was found that protein transport through functionally isolated, “patched” NPCs depended on signal sequences, extracts, and metabolic energy, as in vivo. All NPCs were competent for both import and export. The transport direction was strictly determined by the transport signal, and at none of the conditions explored was the import protein exported or the export protein imported, even when the application sides of the extracts were reversed. The mean transport rates of the single NPC were ≈2 dimers/s for the import protein and ≈4 dimers/s for the export protein (≈15 μM substrate concentration, 22–24°C), in good agreement with in vivo rates estimated for mammalian cells by microinjection experiments. The study shows that optical single-transporter recording permits the analysis of membrane transport processes not previously accessible to single-transporter recording and thus provides additional possibilities for the elucidation of nucleocytoplasmic transport mechanisms. PMID:10518538

  19. Overexpressing components of the nuclear transport apparatus causes severe growth symptoms in tobacco leaves

    PubMed Central

    Kemp, Clare; Coleman, Alex; Wells, Graeme; Parry, Geraint

    2015-01-01

    Regulating nucleo-cytoplasmic transport of RNA and protein is a key cellular control point. Perturbing the function of plant nuclear transport components can cause significant developmental defects and in this report we add an important line to this evidence. Overexpression of AtRAN1 or AtNUP62 in Nicotiana benthamiana causes significant damage to leaf tissue. This demonstrates that the precise control of nuclear transport is an important aspect of maintaining tissue integrity. PMID:26039465

  20. Multi-Tasking: Nuclear Transcription Factors with Novel Roles in the Mitochondria

    PubMed Central

    Szczepanek, Karol; Lesnefsky, Edward J.; Larner, Andrew C.

    2012-01-01

    Coordinated responses between the nucleus and mitochondria are essential for maintenance of homeostasis. For over 15 years, pools of nuclear transcription factors (TFs), such as p53 and nuclear hormone receptors, have been observed in the mitochondria. The contribution of the mitochondrial pool of these TFs to their well-defined biological actions is in some cases clear and in others not well understood. Recently, a small mitochondrial pool of the TF signal transducer and activator of transcription factor 3 (STAT3) was shown to modulate the activity of the electron transport chain. The mitochondrial function of STAT3 encompasses both its biological actions in the heart as well as its oncogenic effects. This review highlights advances in our understanding of how mitochondrial pools of nuclear TFs may influence the function of this organelle. PMID:22705015

  1. Novel properties of the protein kinase CK2-site-regulated nuclear- localization sequence of the interferon-induced nuclear factor IFI 16.

    PubMed Central

    Briggs, L J; Johnstone, R W; Elliot, R M; Xiao, C Y; Dawson, M; Trapani, J A; Jans, D A

    2001-01-01

    Members of the interferon-induced class of nuclear factors possess a putative CcN motif, comparable with that within proteins such as the simian virus 40 large tumour antigen (T-ag), which confers phosphorylation-mediated regulation of nuclear-localization sequence (NLS)-dependent nuclear import. Here we examine the functionality of the interferon-induced factor 16 (IFI 16) CcN motif, demonstrating its ability to target a heterologous protein to the nucleus, and to be phosphorylated specifically by the CcN-motif-phosphorylating protein kinase CK2 (CK2). The IFI 16 NLS, however, has novel properties, conferring ATP-dependent nuclear import completely independent of cytosolic factors, as well as binding to nuclear components. The IFI 16 NLS is not recognized with high affinity by the NLS-binding importin heterodimer, and transport mediated by it is insensitive to non-hydrolysable GTP analogues. The IFI 16 NLS thus mediates nuclear import through a pathway completely distinct from that of conventional NLSs, such as that of T-ag, but intriguingly resembling that of the NLS of the HIV-1 transactivator protein Tat. Since the IFI 16 CK2 site enhances nuclear import through facilitating binding to nuclear components, this represents a novel mechanism by which the site regulates nuclear-protein import, and constitutes a difference between the IFI 16 and Tat NLSs that may be of importance in the immune response. PMID:11115400

  2. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. PMID:27114368

  3. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system.

  4. Both ran and importins have the ability to function as nuclear mRNA export factors.

    PubMed Central

    Yi, Rui; Bogerd, Hal P; Wiegand, Heather L; Cullen, Bryan R

    2002-01-01

    The Ran protein regulates nucleocytoplasmic transport mediated by the karyopherin family of nuclear transport factors. Ran is converted to the active, GTP bound form in the nucleus and then binds to a conserved domain found in all karyopherins. This interaction induces cargo binding for exportins and cargo release for importins. In either case, the Ran.GTP is then transported to the cytoplasm by the karyopherin, where it is hydrolyzed to Ran.GDP. To ask whether Ran could function as a nuclear mRNA export factor, we fused Ran to the MS2 coat protein and inserted MS2 RNA-binding sites into an unspliced cat mRNA that is normally sequestered in the nucleus. Coexpression of MS2-Ran induced cat mRNA export and CAT enzyme expression as effectively as, for example, an MS2-Rev fusion protein. MS2-Ran dependent nuclear mRNA export was reduced by inhibitors specific for Crm1, but not blocked as was seen with MS2-Rev. Consistent with the hypothesis that Crm1 is not the only karyopherin cofactor for MS2-Ran mediated mRNA export, we show that not only Crm1 but also CAS, transportin, importin beta and exportin t can all export mRNA from the nucleus when tethered via the MS2 RNA-binding domain. In contrast, two shuttling hnRNPs, hnRNP A1 and hnRNP K, proved unable to function as nuclear RNA export factors when expressed as MS2 fusions. Together, these data argue that karyopherins that normally function to transport proteins into or out of the nucleus are also capable of exporting tethered mRNA molecules. PMID:11911364

  5. Nuclear modification factor using Tsallis non-extensive statistics

    NASA Astrophysics Data System (ADS)

    Tripathy, Sushanta; Bhattacharyya, Trambak; Garg, Prakhar; Kumar, Prateek; Sahoo, Raghunath; Cleymans, Jean

    2016-09-01

    The nuclear modification factor is derived using Tsallis non-extensive statistics in relaxation time approximation. The variation of the nuclear modification factor with transverse momentum for different values of the non-extensive parameter, q, is also observed. The experimental data from RHIC and LHC are analysed in the framework of Tsallis non-extensive statistics in a relaxation time approximation. It is shown that the proposed approach explains the R_{AA} of all particles over a wide range of transverse momentum but does not seem to describe the rise in R_{AA} at very high transverse momenta.

  6. Economic Conditions and Factors Affecting New Nuclear Power Deployment

    SciTech Connect

    Harrison, Thomas J.

    2014-10-01

    This report documents work performed in support of the US Department of Energy Office of Nuclear Energy’s Advanced Small Modular Reactor (AdvSMR) program. The report presents information and results from economic analyses to describe current electricity market conditions and those key factors that may impact the deployment of AdvSMRs or any other new nuclear power plants. Thus, this report serves as a reference document for DOE as it moves forward with its plans to develop advanced reactors, including AdvSMRs. For the purpose of this analysis, information on electricity markets and nuclear power plant operating costs will be combined to examine the current state of the nuclear industry and the process required to successfully move forward with new nuclear power in general and AdvSMRs in particular. The current electricity market is generally unfavorable to new nuclear construction, especially in deregulated markets with heavy competition from natural gas and subsidized renewables. The successful and profitable operation of a nuclear power plant (or any power plant) requires the rate at which the electricity is sold to be sufficiently greater than the cost to operate. The wholesale rates in most US markets have settled into values that provide profits for most operating nuclear power plants but are too low to support the added cost of capital recovery for new nuclear construction. There is a strong geographic dependence on the wholesale rate, with some markets currently able to support new nuclear construction. However, there is also a strong geographic dependence on pronuclear public opinion; the areas where power prices are high tend to have unfavorable views on the construction of new nuclear power plants. The use of government-backed incentives, such as subsidies, can help provide a margin to help justify construction projects that otherwise may not seem viable. Similarly, low interest rates for the project will also add a positive margin to the economic

  7. 75 FR 75641 - Advance Notification to Native American Tribes of Transportation of Certain Types of Nuclear Waste

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-06

    ... notification to Native American Tribes of transportation of certain types of nuclear waste (64 FR 71331... Tribes of Transportation of Certain Types of Nuclear Waste AGENCY: Nuclear Regulatory Commission. ACTION...'s designee, of certain shipments of irradiated reactor fuel and certain nuclear waste...

  8. Cytokinin response factors regulate PIN-FORMED auxin transporters.

    PubMed

    Šimášková, Mária; O'Brien, José Antonio; Khan, Mamoona; Van Noorden, Giel; Ötvös, Krisztina; Vieten, Anne; De Clercq, Inge; Van Haperen, Johanna Maria Adriana; Cuesta, Candela; Hoyerová, Klára; Vanneste, Steffen; Marhavý, Peter; Wabnik, Krzysztof; Van Breusegem, Frank; Nowack, Moritz; Murphy, Angus; Friml, Jiří; Weijers, Dolf; Beeckman, Tom; Benková, Eva

    2015-11-06

    Auxin and cytokinin are key endogenous regulators of plant development. Although cytokinin-mediated modulation of auxin distribution is a developmentally crucial hormonal interaction, its molecular basis is largely unknown. Here we show a direct regulatory link between cytokinin signalling and the auxin transport machinery uncovering a mechanistic framework for cytokinin-auxin cross-talk. We show that the CYTOKININ RESPONSE FACTORS (CRFs), transcription factors downstream of cytokinin perception, transcriptionally control genes encoding PIN-FORMED (PIN) auxin transporters at a specific PIN CYTOKININ RESPONSE ELEMENT (PCRE) domain. Removal of this cis-regulatory element effectively uncouples PIN transcription from the CRF-mediated cytokinin regulation and attenuates plant cytokinin sensitivity. We propose that CRFs represent a missing cross-talk component that fine-tunes auxin transport capacity downstream of cytokinin signalling to control plant development.

  9. Recombinant modular transporters on the basis of epidermal growth factor for targeted intracellular delivery of photosensitizers

    NASA Astrophysics Data System (ADS)

    Gilyazova, Dinara G.; Rosenkranz, Andrey A.; Gulak, Pavel V.; Lunin, Vladimir G.; Sergienko, Olga V.; Grin, Mikhail A.; Mironov, Andrey F.; Rubin, Andrey B.; Sobolev, Alexander S.

    2005-08-01

    The search for new pharmaceuticals has raised interest in locally-acting drugs which act over short distances within the cell, and for which different cell compartments have different sensitivities. Thus, photosensitizers used in anti-cancer therapy should be transported to the most sensitive subcellular compartments where their action is most pronounced. Earlier, we described the effects of bacterially expressed modular recombinant transporters for photosensitizers comprising a-melanocyte-stimulating hormone as an internalizable, cell-specific ligand, an optimized nuclear localization sequence, an Escherichia coli hemoglobin-like protein as a carrier, and an endosomolytic amphipathic polypeptide. These transporters delivered photosensitizers into the murine melanoma cells nuclei to result in cytotoxic effects 2 orders of magnitude greater than those of nonmodified photosensitizers. Here we describe new transporters possessing the same modules except for a ligand that is replaced with epidermal growth factor specific for other cancer cell types. The new transporter modules retained their functional activities within the chimera, this transporter delivered photosensitizers into the human carcinoma cells nuclei to result in photocytotoxic effects almost 3 orders of magnitude greater than those of nonmodified photosensitizers. The obtained results show that ligand modules of such transporters are interchangeable, meaning that they can be tailored for particular applications.

  10. Factors controlling radionuclide transport behavior in a generic geological radioactive waste repository

    NASA Astrophysics Data System (ADS)

    Bianchi, M.; Liu, H.; Birkholzer, J. T.

    2013-12-01

    One of the main challenges in designing a geological repository for high-level nuclear waste is the assessment of postclosure safety, which involves the long-term ability of the engineered system and the geological host formation to contain and delay the leakage of radionuclides toward the biosphere. A correct assessment requires detailed knowledge of the factors controlling radionuclide transport in the different components of the geological disposal system. For instance, molecular diffusion, which is considered the dominant transport mechanism in low-permeable geological formations, may be influenced by the heterogeneity of the diffusive parameters and by electrochemical processes. Likewise, the prevalence of advective transport in the near-field excavation damaged zone (EDZ) may be controlled by the hydrogeological conditions in the host formation, as well as by hydrogeological and geometrical properties. In this study, we performed two-dimensional numerical simulations of groundwater flow and radionuclide transport to study the influence of several factors on the prevailing transport mechanism (i.e., advection or molecular diffusion) in the different components of a geological nuclear waste repository system. Particular attention was given to the excavation damaged zone (EDZ) around the repository tunnels and access shaft, which was modeled as a single effective continuum as well as with the dual-porosity approach. We considered different hydrogeological and geometrical factors, including the ambient hydraulic gradient, the presence of groundwater pressure anomalies, and the thickness of the EDZ and its hydraulic properties. By comparing simulation results, we show that transport behavior and the role of the EDZ as a preferential flow path for radionuclide transport is most sensitive to the hydrogeological conditions in the host rock. When the hydraulic gradient in the host rock is reduced by a factor of 5 from the unit value, we observe a significant reduction

  11. Personality Factors and Nuclear Power Plant Operators: Initial License Success

    NASA Astrophysics Data System (ADS)

    DeVita-Cochrane, Cynthia

    Commercial nuclear power utilities are under pressure to effectively recruit and retain licensed reactor operators in light of poor candidate training completion rates and recent candidate failures on the Nuclear Regulatory Commission (NRC) license exam. One candidate failure can cost a utility over $400,000, making the successful licensing of new operators a critical path to operational excellence. This study was designed to discover if the NEO-PI-3, a 5-factor measure of personality, could improve selection in nuclear utilities by identifying personality factors that predict license candidate success. Two large U.S. commercial nuclear power corporations provided potential participant contact information and candidate results on the 2014 NRC exam from their nuclear power units nation-wide. License candidates who participated (n = 75) completed the NEO-PI-3 personality test and results were compared to 3 outcomes on the NRC exam: written exam, simulated operating exam, and overall exam result. Significant correlations were found between several personality factors and both written and operating exam outcomes on the NRC exam. Further, a regression analysis indicated that personality factors, particularly Conscientiousness, predicted simulated operating exam scores. The results of this study may be used to support the use of the NEO-PI-3 to improve operator selection as an addition to the current selection protocol. Positive social change implications from this study include support for the use of a personality measure by utilities to improve their return-on-investment in candidates and by individual candidates to avoid career failures. The results of this study may also positively impact the public by supporting the safe and reliable operation of commercial nuclear power utilities in the United States.

  12. Electronic and Nuclear Factors in Charge and Excitation Transfer

    SciTech Connect

    Piotr Piotrowiak

    2004-09-28

    We report the and/or state of several subprojects of our DOE sponsored research on Electronic and Nuclear Factors in Electron and Excitation Transfer: (1) Construction of an ultrafast Ti:sapphire amplifier. (2) Mediation of electronic interactions in host-guest molecules. (3) Theoretical models of electrolytes in weakly polar media. (4) Symmetry effects in intramolecular excitation transfer.

  13. Summary report on transportation of nuclear fuel materials in Japan : transportation infrastructure, threats identified in open literature, and physical protection regulations.

    SciTech Connect

    Cochran, John Russell; Ouchi, Yuichiro; Furaus, James Phillip; Marincel, Michelle K.

    2008-03-01

    This report summarizes the results of three detailed studies of the physical protection systems for the protection of nuclear materials transport in Japan, with an emphasis on the transportation of mixed oxide fuel materials1. The Japanese infrastructure for transporting nuclear fuel materials is addressed in the first section. The second section of this report presents a summary of baseline data from the open literature on the threats of sabotage and theft during the transport of nuclear fuel materials in Japan. The third section summarizes a review of current International Atomic Energy Agency, Japanese and United States guidelines and regulations concerning the physical protection for the transportation of nuclear fuel materials.

  14. Development and Analysis of Advanced High-Temperature Technology for Nuclear Heat Transport and Power Conversion

    SciTech Connect

    Per F. Peterson

    2010-03-01

    This project by the Thermal Hydraulics Research Laboratory at U.C. Berkeley Studied advanced high-temperature heat transport and power conversion technology, in support of the Nuclear Hydrogen Initiative and Generation IV.

  15. Critical design factors for sector transport maintenance in DEMO

    NASA Astrophysics Data System (ADS)

    Utoh, Hiroyasu; Someya, Youji; Tobita, Kenji; Asakura, Nobuyuki; Hoshino, Kazuo; Nakamura, Makoto

    2013-12-01

    This paper mainly focuses on a sector transport maintenance scheme from the aspects of high plant availability. In this study, three different maintenance schemes are considered based on (1) the number of maintenance ports and (2) the insertion direction. The design study clarifies critical design factors and key engineering issues on the maintenance scheme: (1) how to support an enormous overturning force of the toroidal field coils in the large open port for sector transport and (2) define the transferring mechanism of sectors in the vacuum vessel. On reviewing these assessment factors, the sector transport using a limited number of horizontal maintenance ports is found to be a more realistic maintenance scheme. In addition, evaluating maintenance scenarios under high decay heat is proposed for the first time. The key design factors are the cool-down time in the reactor and the cooling method in the maintenance scheme to keep components under operational temperature. Based on one-dimensional heat conduction analysis, after one month cool-down time, each sector of SlimCS could be transported to the hot cell facility by gas cooling.

  16. Hepatocyte uptake and nuclear binding of epidermal growth factor (EGF)

    SciTech Connect

    Moriarity, D.M.; Underwood, T.

    1987-05-01

    The internalization of /sup 125/I-EGF and its cell-membrane receptor by target cells suggests a possible intracellular role for EGF and/or its receptor. They have examined the uptake of /sup 125/I-EGF by primary cultures of adult rat hepatocytes after 1, 24 and 48 hours of incubation in the presence of the growth factor. A significant increase in the association of radioactivity with various nuclear fractions was observed between 1 and 24 hours incubation. After 1 hour approximately 2% of the total specific binding was associated with both the nuclear sap proteins extractable with 0.14 M NaCl and with the residual nucleoplasm, while about 1% or less was associated with the nuclear membrane and the chromatin fractions. After 24 hours the percentage associated with the nuclear membrane and chromatin fractions increased 2-4 fold. Binding of /sup 125/I-EGF to isolated nuclei from intact livers of adult rats followed by fractionation of the nuclei after incubation with /sup 125/I-EGF indicated that after 60 min at 37/sup 0/C there was a substantial amount of specific binding associated with the nucleoplasm, nuclear membranes and chromatin fractions. These data indicate that specific interactions of EGF with nuclear components occur in both intact normal hepatocytes and in isolated nuclei from intact liver.

  17. Methamphetamine oxidative stress, neurotoxicity, and functional deficits are modulated by nuclear factor-E2-related factor 2.

    PubMed

    Ramkissoon, Annmarie; Wells, Peter G

    2015-12-01

    Activation of redox-sensitive transcription factors like nuclear factor-E2-related factor 2 (Nrf2) can enhance the transcription of cytoprotective genes during oxidative stress. We investigated whether Nrf2 is activated by methamphetamine (METH) thereby altering neurotoxicity in Nrf2 +/+ and -/- adult mouse brain. A single dose of METH can induce the mRNA levels of Nrf2-regulated antioxidant and cytoprotective proteins in mouse brain. Multiple-day dosing with METH enhanced DNA oxidation and decreased tyrosine hydroxylase and dopamine transporter staining in the striatum, indicating dopaminergic nerve terminal toxicity, which was more severe in -/- mice, as were deficits in motor coordination and olfactory discrimination. These Nrf2-dependent effects were independent of changes in METH metabolism or the induction of hyperthermia. Similarly, METH increased striatal glial fibrillary acidic protein, indicating neurotoxicity. METH neurotoxicity was also observed in the glial cells and in the GABAergic system of the olfactory bulbs and was enhanced in -/- mice, whereas dopaminergic parameters were unaffected. With one-day dosing of METH, there were no differences between +/+ and -/- mice in either basal or METH-enhanced DNA oxidation and neurotoxicity markers. Nrf2-mediated pathways accordingly may protect against the neurodegenerative effects and functional deficits initiated by METH and perhaps other reactive oxygen species-enhancing neurotoxicants, when there is time for transcriptional activation and protein induction. In human users of METH, this mechanism may be essential when differences in drug abuse patterns may alter the induction and duration of Nrf2 activation thereby modulating susceptibility to the neurotoxic effects of METH.

  18. Monocarboxylate transporter 1 contributes to growth factor-induced tumor cell migration independent of transporter activity

    PubMed Central

    Gray, Alana L.; Coleman, David T.; Shi, Runhua; Cardelli, James A.

    2016-01-01

    Tumor progression to metastatic disease contributes to the vast majority of incurable cancer. Understanding the processes leading to advanced stage cancer is important for the development of future therapeutic strategies. Here, we establish a connection between tumor cell migration, a prerequisite to metastasis, and monocarboxylate transporter 1 (MCT1). MCT1 transporter activity is known to regulate aspects of tumor progression and, as such, is a clinically relevant target for treating cancer. Knockdown of MCT1 expression caused decreased hepatocyte growth factor (HGF)-induced as well as epidermal growth factor (EGF)-induced tumor cell scattering and wound healing. Western blot analysis suggested that MCT1 knockdown (KD) hinders signaling through the HGF receptor (c-Met) but not the EGF receptor. Exogenous, membrane-permeable MCT1 substrates were not able to rescue motility in MCT1 KD cells, nor was pharmacologic inhibition of MCT1 able to recapitulate decreased cell motility as seen with MCT1 KD cells, indicating transporter activity of MCT1 was dispensable for EGF- and HGF-induced motility. These results indicate MCT1 expression, independent of transporter activity, is required for growth factor-induced tumor cell motility. The findings presented herein suggest a novel function for MCT1 in tumor progression independent of its role as a monocarboxylate transporter. PMID:27127175

  19. An overview of a nuclear reprocessing plant Human Factors programme.

    PubMed

    Kirwan, Barry

    2003-09-01

    This paper presents a case study of a large Human Factors programme applied in the nuclear fuel reprocessing industry (1987-1991). The paper outlines the key Human Factors issues addressed, as well as the impacts achieved, and gives an indication of the resources utilised (approximately 15 person-years of effort). It also considers the starting point of the programme, in terms of the factors that led to the need for such an extensive programme. Some general lessons learned are given at the end of the paper. PMID:12963330

  20. Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion

    PubMed Central

    Bosse, Jens B.; Hogue, Ian B.; Feric, Marina; Thiberge, Stephan Y.; Sodeik, Beate; Brangwynne, Clifford P.; Enquist, Lynn W.

    2015-01-01

    The nuclear chromatin structure confines the movement of large macromolecular complexes to interchromatin corrals. Herpesvirus capsids of approximately 125 nm assemble in the nucleoplasm and must reach the nuclear membranes for egress. Previous studies concluded that nuclear herpesvirus capsid motility is active, directed, and based on nuclear filamentous actin, suggesting that large nuclear complexes need metabolic energy to escape nuclear entrapment. However, this hypothesis has recently been challenged. Commonly used microscopy techniques do not allow the imaging of rapid nuclear particle motility with sufficient spatiotemporal resolution. Here, we use a rotating, oblique light sheet, which we dubbed a ring-sheet, to image and track viral capsids with high temporal and spatial resolution. We do not find any evidence for directed transport. Instead, infection with different herpesviruses induced an enlargement of interchromatin domains and allowed particles to diffuse unrestricted over longer distances, thereby facilitating nuclear egress for a larger fraction of capsids. PMID:26438852

  1. Remodeling nuclear architecture allows efficient transport of herpesvirus capsids by diffusion.

    PubMed

    Bosse, Jens B; Hogue, Ian B; Feric, Marina; Thiberge, Stephan Y; Sodeik, Beate; Brangwynne, Clifford P; Enquist, Lynn W

    2015-10-20

    The nuclear chromatin structure confines the movement of large macromolecular complexes to interchromatin corrals. Herpesvirus capsids of approximately 125 nm assemble in the nucleoplasm and must reach the nuclear membranes for egress. Previous studies concluded that nuclear herpesvirus capsid motility is active, directed, and based on nuclear filamentous actin, suggesting that large nuclear complexes need metabolic energy to escape nuclear entrapment. However, this hypothesis has recently been challenged. Commonly used microscopy techniques do not allow the imaging of rapid nuclear particle motility with sufficient spatiotemporal resolution. Here, we use a rotating, oblique light sheet, which we dubbed a ring-sheet, to image and track viral capsids with high temporal and spatial resolution. We do not find any evidence for directed transport. Instead, infection with different herpesviruses induced an enlargement of interchromatin domains and allowed particles to diffuse unrestricted over longer distances, thereby facilitating nuclear egress for a larger fraction of capsids. PMID:26438852

  2. Nuclear transport of paxillin depends on focal adhesion dynamics and FAT domains

    PubMed Central

    Sathe, Aneesh R.; Shivashankar, G. V.; Sheetz, Michael P.

    2016-01-01

    ABSTRACT The nuclear transport of paxillin appears to be crucial for paxillin function but the mechanism of transport remains unclear. Here, we show that the nuclear transport of paxillin is regulated by focal adhesion turnover and the presence of FAT domains. Focal adhesion turnover was controlled using triangular or circular fibronectin islands. Circular islands caused higher focal adhesion turnover and increased the nuclear transport of paxillin relative to triangular islands. Mutating several residues of paxillin had no effect on its nuclear transport, suggesting that the process is controlled by multiple domains. Knocking out FAK (also known as PTK2) and vinculin caused an increase in nuclear paxillin. This could be reversed by rescue with wild-type FAK but not by FAK with a mutated FAT domain, which inhibits paxillin binding. Expressing just the FAT domain of FAK not only brought down nuclear levels of paxillin but also caused a large immobile fraction of paxillin to be present at focal adhesions, as demonstrated by fluorescence recovery after photobleaching (FRAP) studies. Taken together, focal adhesion turnover and FAT domains regulate the nuclear localization of paxillin, suggesting a possible role for transcriptional control, through paxillin, by focal adhesions. PMID:27068537

  3. Using Nuclear Theory, Data and Uncertainties in Monte Carlo Transport Applications

    SciTech Connect

    Rising, Michael Evan

    2015-11-03

    These are slides for a presentation on using nuclear theory, data and uncertainties in Monte Carlo transport applications. The following topics are covered: nuclear data (experimental data versus theoretical models, data evaluation and uncertainty quantification), fission multiplicity models (fixed source applications, criticality calculations), uncertainties and their impact (integral quantities, sensitivity analysis, uncertainty propagation).

  4. Factors affecting recognition of cancer risks of nuclear workers.

    PubMed Central

    Kneale, G W; Stewart, A M

    1995-01-01

    OBJECTIVES--To discover whether direct estimates of the risks of cancer for nuclear workers agree with indirect estimates based on survivors of the atomic bomb; whether relations between age at exposure and risk of cancer are the same for workers and survivors, and whether dosimetry standards are sufficiently uniform to allow pooling of data from different nuclear industrial sites. METHOD--Data from five nuclear sites in the United States were included in a cohort analysis that as well as controlling for all the usual factors also allowed for possible effects of three cancer modulating factors (exposure age, cancer latency, and year of exposure). This analysis was first applied to three distinct cohorts, and then to two sets of pooled data. RESULTS--From each study cohort there was evidence of a risk of cancer related to dose, and evidence that the extra radiogenic cancers had the same overall histological manifestations as naturally occurring cancers and were largely the result of exposures after 50 years of age causing deaths after 70 years. There were, however, significant differences between the five sets of risk estimates. CONCLUSIONS--Although the risks of cancer in nuclear workers were appreciably higher than estimates based on the cancer experiences of survivors of the atomic bomb, some uncertainties remained as there were non-uniform standards of dosimetry in the nuclear sites. The differences between nuclear workers and survivors of the atomic bomb were largely the result of relations between age at exposure and risk of cancer being totally different for workers and survivors and, in the occupational data, there were no signs of the special risks of leukaemia found in atomic bomb data and other studies of effects of high doses. PMID:7663636

  5. Molecular Characterization and Functional Analysis of Annulate Lamellae Pore Complexes in Nuclear Transport in Mammalian Cells

    PubMed Central

    Raghunayakula, Sarita; Subramonian, Divya; Dasso, Mary; Kumar, Rita; Zhang, Xiang-Dong

    2015-01-01

    Annulate lamellae are cytoplasmic organelles containing stacked sheets of membranes embedded with pore complexes. These cytoplasmic pore complexes at annulate lamellae are morphologically similar to nuclear pore complexes at the nuclear envelope. Although annulate lamellae has been observed in nearly all types of cells, their biological functions are still largely unknown. Here we show that SUMO1-modification of the Ran GTPase-activating protein RanGAP1 not only target RanGAP1 to its known sites at nuclear pore complexes but also to annulate lamellae pore complexes through interactions with the Ran-binding protein RanBP2 and the SUMO-conjugating enzyme Ubc9 in mammalian cells. Furthermore, upregulation of annulate lamellae, which decreases the number of nuclear pore complexes and concurrently increases that of annulate lamellae pore complexes, causes a redistribution of nuclear transport receptors including importin α/β and the exportin CRM1 from nuclear pore complexes to annulate lamellae pore complexes and also reduces the rates of nuclear import and export. Moreover, our results reveal that importin α/β-mediated import complexes initially accumulate at annulate lamellae pore complexes upon the activation of nuclear import and subsequently disassociate for nuclear import through nuclear pore complexes in cells with upregulation of annulate lamellae. Lastly, CRM1-mediated export complexes are concentrated at both nuclear pore complexes and annulate lamellae pore complexes when the disassembly of these export complexes is inhibited by transient expression of a Ran GTPase mutant arrested in its GTP-bound form, suggesting that RanGAP1/RanBP2-activated RanGTP hydrolysis at these pore complexes is required for the dissociation of the export complexes. Hence, our findings provide a foundation for further investigation of how upregulation of annulate lamellae decreases the rates of nuclear transport and also for elucidation of the biological significance of the

  6. Molecular Characterization and Functional Analysis of Annulate Lamellae Pore Complexes in Nuclear Transport in Mammalian Cells.

    PubMed

    Raghunayakula, Sarita; Subramonian, Divya; Dasso, Mary; Kumar, Rita; Zhang, Xiang-Dong

    2015-01-01

    Annulate lamellae are cytoplasmic organelles containing stacked sheets of membranes embedded with pore complexes. These cytoplasmic pore complexes at annulate lamellae are morphologically similar to nuclear pore complexes at the nuclear envelope. Although annulate lamellae has been observed in nearly all types of cells, their biological functions are still largely unknown. Here we show that SUMO1-modification of the Ran GTPase-activating protein RanGAP1 not only target RanGAP1 to its known sites at nuclear pore complexes but also to annulate lamellae pore complexes through interactions with the Ran-binding protein RanBP2 and the SUMO-conjugating enzyme Ubc9 in mammalian cells. Furthermore, upregulation of annulate lamellae, which decreases the number of nuclear pore complexes and concurrently increases that of annulate lamellae pore complexes, causes a redistribution of nuclear transport receptors including importin α/β and the exportin CRM1 from nuclear pore complexes to annulate lamellae pore complexes and also reduces the rates of nuclear import and export. Moreover, our results reveal that importin α/β-mediated import complexes initially accumulate at annulate lamellae pore complexes upon the activation of nuclear import and subsequently disassociate for nuclear import through nuclear pore complexes in cells with upregulation of annulate lamellae. Lastly, CRM1-mediated export complexes are concentrated at both nuclear pore complexes and annulate lamellae pore complexes when the disassembly of these export complexes is inhibited by transient expression of a Ran GTPase mutant arrested in its GTP-bound form, suggesting that RanGAP1/RanBP2-activated RanGTP hydrolysis at these pore complexes is required for the dissociation of the export complexes. Hence, our findings provide a foundation for further investigation of how upregulation of annulate lamellae decreases the rates of nuclear transport and also for elucidation of the biological significance of the

  7. Regulated nuclear export of the homeodomain transcription factor Prospero.

    PubMed

    Demidenko, Z; Badenhorst, P; Jones, T; Bi, X; Mortin, M A

    2001-04-01

    Subcellular distribution of the Prospero protein is dynamically regulated during Drosophila embryonic nervous system development. Prospero is first detected in neuroblasts where it becomes cortically localized and tethered by the adapter protein, Miranda. After division, Prospero enters the nucleus of daughter ganglion mother cells where it functions as a transcription factor. We have isolated a mutation that removes the C-terminal 30 amino acids from the highly conserved 100 amino acid Prospero domain. Molecular dissection of the homeo- and Prospero domains, and expression of chimeric Prospero proteins in mammalian and insect cultured cells indicates that Prospero contains a nuclear export signal that is masked by the Prospero domain. Nuclear export of Prospero, which is sensitive to the drug leptomycin B, is mediated by Exportin. Mutation of the nuclear export signal-mask in Drosophila embryos prevents Prospero nuclear localization in ganglion mother cells. We propose that a combination of cortical tethering and regulated nuclear export controls Prospero subcellular distribution and function in all higher eukaryotes. PMID:11262236

  8. RISKIND: A computer program for calculating radiological consequences and health risks from transportation of spent nuclear fuel

    SciTech Connect

    Yuan, Y.C.; Chen, S.Y.; LePoire, D.J.; Rothman, R.

    1993-02-01

    This report presents the technical details of RISIUND, a computer code designed to estimate potential radiological consequences and health risks to individuals and the collective population from exposures associated with the transportation of spent nuclear fuel. RISKIND is a user-friendly, semiinteractive program that can be run on an IBM or equivalent personal computer. The program language is FORTRAN-77. Several models are included in RISKIND that have been tailored to calculate the exposure to individuals under various incident-free and accident conditions. The incidentfree models assess exposures from both gamma and neutron radiation and can account for different cask designs. The accident models include accidental release, atmospheric transport, and the environmental pathways of radionuclides from spent fuels; these models also assess health risks to individuals and the collective population. The models are supported by databases that are specific to spent nuclear fuels and include a radionudide inventory and dose conversion factors.

  9. The role of ligand density and size in mediating quantum dot nuclear transport.

    PubMed

    Tang, Peter S; Sathiamoorthy, Sarmitha; Lustig, Lindsay C; Ponzielli, Romina; Inamoto, Ichiro; Penn, Linda Z; Shin, Jumi A; Chan, Warren C W

    2014-10-29

    Studying the effects of the physicochemical properties of nanomaterials on cellular uptake, toxicity, and exocytosis can provide the foundation for designing safer and more effective nanoparticles for clinical applications. However, an understanding of the effects of these properties on subcellular transport, accumulation, and distribution remains limited. The present study investigates the effects of surface density and particle size of semiconductor quantum dots on cellular uptake as well as nuclear transport kinetics, retention, and accumulation. The current work illustrates that cellular uptake and nuclear accumulation of nanoparticles depend on surface density of the nuclear localization signal (NLS) peptides with nuclear transport reaching a plateau at 20% surface NLS density in as little as 30 min. These intracellular nanoparticles have no effects on cell viability up to 72 h post treatment. These findings will set a foundation for engineering more sophisticated nanoparticle systems for imaging and manipulating genetic targets in the nucleus.

  10. Nanoscale stiffness topography reveals structure and mechanics of the transport barrier in intact nuclear pore complexes

    PubMed Central

    Labokha, Aksana A.; Osmanović, Dino; Liashkovich, Ivan; Orlova, Elena V.; Ford, Ian J.; Charras, Guillaume; Fassati, Ariberto; Hoogenboom, Bart W.

    2014-01-01

    The nuclear pore complex (NPC) is the gate for transport between the cell nucleus and the cytoplasm. Small molecules cross the NPC by passive diffusion, but molecules larger than ~5 nm must bind to nuclear transport receptors to overcome a selective barrier within the NPC1. Whilst the structure and shape of the cytoplasmic ring of the NPC are relatively well characterized2-5, the selective barrier is situated deep within the central channel of the NPC and depends critically on unstructured nuclear pore proteins5,6, and is therefore not well understood. Here, we show that stiffness topography7 with sharp atomic force microscopy tips can generate nanoscale cross sections of the NPC. The cross sections reveal two distinct structures, a cytoplasmic ring and a central plug structure, which are consistent with the three-dimensional NPC structure derived from electron microscopy2-5. The central plug persists after reactivation of the transport cycle and resultant cargo release, indicating that the plug is an intrinsic part of the NPC barrier. Added nuclear transport receptors accumulate on the intact transport barrier and lead to a homogenization of the barrier stiffness. The observed nanomechanical properties in the NPC indicate the presence of a cohesive barrier to transport, and are quantitatively consistent with the presence of a central condensate of nuclear pore proteins in the NPC channel. PMID:25420031

  11. Nuclear Energy for a Low-Carbon-Dioxide-Emission Transportation System with Liquid Fuels

    SciTech Connect

    Forsberg, Charles W

    2007-01-01

    The two major energy challenges for the United States are to replace crude oil in our transportation system and reduce greenhouse gas emissions. A multilayer strategy to replace oil using nuclear energy and various carbon sources (fossil fuels, biomass, or air) is described that (a) allows the continued use of liquid fuels (ethanol, gasoline, diesel, and jet fuel) in the transport sector, (b) does not require major changes in lifestyle by the consumer, and (c) ultimately eliminates carbon dioxide emissions from the transport sector. Nuclear energy is used to provide electricity, heat, and ultimately hydrogen, with the hydrogen produced by either electrolysis or more advanced thermochemical production methods. In the near term, nuclear energy can provide low-temperature heat (steam) for ethanol production and electricity for transportation. Midterm options include low-temperature heat and limited quantities of hydrogen for processing cellulosic biomass into liquid fuels (ethanol and lignin-derived hydrocarbons) and providing high-temperature heat for (a) traditional refining and (b) underground oil production and refining. In the longer term, biomass becomes the feedstock for liquid-fuels production, with nuclear energy providing heat and large quantities of hydrogen for complete biomass conversion to hydrocarbon fuels. Nuclear energy could be used to provide over half the total energy required by the transportation system, and the use of oil in the transport sector could potentially be eliminated within several decades.

  12. Fatty Acid-binding Proteins Transport N-Acylethanolamines to Nuclear Receptors and Are Targets of Endocannabinoid Transport Inhibitors*

    PubMed Central

    Kaczocha, Martin; Vivieca, Stephanie; Sun, Jing; Glaser, Sherrye T.; Deutsch, Dale G.

    2012-01-01

    N-Acylethanolamines (NAEs) are bioactive lipids that engage diverse receptor systems. Recently, we identified fatty acid-binding proteins (FABPs) as intracellular NAE carriers. Here, we provide two new functions for FABPs in NAE signaling. We demonstrate that FABPs mediate the nuclear translocation of the NAE oleoylethanolamide, an agonist of nuclear peroxisome proliferator-activated receptor α (PPARα). Antagonism of FABP function through chemical inhibition, dominant-negative approaches, or shRNA-mediated knockdown reduced PPARα activation, confirming a requisite role for FABPs in this process. In addition, we show that NAE analogs, traditionally employed as inhibitors of the putative endocannabinoid transmembrane transporter, target FABPs. Support for the existence of the putative membrane transporter stems primarily from pharmacological inhibition of endocannabinoid uptake by such transport inhibitors, which are widely employed in endocannabinoid research despite lacking a known cellular target(s). Our approach adapted FABP-mediated PPARα signaling and employed in vitro binding, arachidonoyl-[1-14C]ethanolamide ([14C]AEA) uptake, and FABP knockdown to demonstrate that transport inhibitors exert their effects through inhibition of FABPs, thereby providing a molecular rationale for the underlying physiological effects of these compounds. Identification of FABPs as targets of transport inhibitors undermines the central pharmacological support for the existence of an endocannabinoid transmembrane transporter. PMID:22170058

  13. Effect of aminoguanidine on lipopolysaccharide-induced changes in rat liver transporters and transcription factors.

    PubMed

    Aoki, Kimiko; Nakajima, Miki; Hoshi, Yoshiyuki; Saso, Naomi; Kato, Satoko; Sugiyama, Yuichi; Sato, Hitoshi

    2008-03-01

    To determine the role of nitric oxide (NO) in rat liver transporter regulation, we investigated whether NO mediates lipopolysaccharide (LPS)-induced changes in transporters and their transcription factor expression using aminoguanidine (AG), an inhibitor of induced nitric oxide synthase (iNOS). We confirmed that LPS decreased mRNA levels for Ntcp, Oatp1, Oatp2, Oatp4, Oct1, Mrp2, Mdr1a and increased those for Mdr1b at 16 h after administration. AG attenuated these decreases for Ntcp, Oatp1 and Oatp4 (retinoid X receptor (RXR)alpha- and hepatocyte nuclear factor (HNF)4alpha-dependent genes) and increase for Mdr1b (nuclear factor (NF)-kappaB-dependent gene). Concomitantly, it suppressed LPS-induced NF-kappaB-dependent gene transcription, such as those for proinflammatory cytokines (cytokines; tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6) and iNOS, and also suppressed IL-1beta release from Kupffer cells (KCs) at post-translational levels, but had little effect on the LPS-induced decreases in RXRalpha and HNF4alpha transcriptional activities. These findings indicate that hepatocytes were stimulated directly by LPS, which lead to the activation of NF-kappaB and reduction of RXRalpha and HNF4alpha transcriptional activities as early responses, and indirectly by cytokines and NO released from KCs via activation of NF-kappaB by LPS as delayed responses. We conclude that AG, which suppresses LPS-induced NF-kappaB activation in both hepatocytes and KCs and then the release of cytokines and NO from KCs, attenuates LPS-induced changes of Ntcp, Oatp1, Oatp4 and Mdr1b transcription in hepatocytes. The roles of cytokines and NO could not be distinguished, however. Further in vitro study is needed to clarify the role of NO in transporter regulation. PMID:18310902

  14. A Transportation Risk Assessment Tool for Analyzing the Transport of Spent Nuclear Fuel and High-Level Radioactive Waste to the Proposed Yucca Mountain Repository

    SciTech Connect

    Ralph Best; T. Winnard; S. Ross; R. Best

    2001-08-17

    The Yucca Mountain Transportation Database was developed as a data management tool for assembling and integrating data from multiple sources to compile the potential transportation impacts presented in the Draft Environmental Impact Statement for a Geologic Repository for the Disposal of Spent Nuclear Fuel and High-Level Radioactive Waste at Yucca Mountain, Nye County, Nevada (DEIS). The database uses the results from existing models and codes such as RADTRAN, RISKIND, INTERLINE, and HIGHWAY to estimate transportation-related impacts of transporting spent nuclear fuel and high-level radioactive waste from commercial reactors and U. S. Department of Energy (DOE) facilities to Yucca Mountain. The source tables in the database are compendiums of information from many diverse sources including: radionuclide quantities for each waste type; route and route characteristics for rail, legal-weight truck, heavy haul. truck, and barge transport options; state-specific accident and fatality rates for routes selected for analysis; packaging and shipment data by waste type; unit risk factors; the complex behavior of the packaged waste forms in severe transport accidents; and the effects of exposure to radiation or the isotopic specific effects of radionclides should they be released in severe transportation accidents. The database works together with the codes RADTRAN (Neuhauser, et al, 1994) and RISKlND (Yuan, et al, 1995) to calculate incident-free dose and accident risk. For the incident-free transportation scenario, the database uses RADTRAN and RISKIND-generated data to calculate doses to offlink populations, onlink populations, people at stops, crews, inspectors, workers at intermodal transfer stations, guards at overnight stops, and escorts, as well as non-radioactive pollution health effects. For accident scenarios, the database uses RADTRAN-generated data to calculate dose risks based on ingestion, inhalation, resuspension, immersion (cloudshine), and groundshine as

  15. Leak-Path Factor Analysis for the Nuclear Materials Storage Facility

    SciTech Connect

    Shaffer, C.; Leonard, M.

    1999-06-13

    Leak-path factors (LPFs) were calculated for the Nuclear Materials Storage Facility (NMSF) located in the Plutonium Facility, Building 41 at the Los Alamos National Laboratory Technical Area 55. In the unlikely event of an accidental fire powerful enough to fail a container holding actinides, the subsequent release of oxides, modeled as PuO{sub 2} aerosols, from the facility and into the surrounding environment was predicted. A 1-h nondestructive assay (NDA) laboratory fire accident was simulated with the MELCOR severe accident analysis code. Fire-driven air movement along with wind-driven air infiltration transported a portion of these actinides from the building. This fraction is referred to as the leak-path factor. The potential effect of smoke aerosol on the transport of the actinides was investigated to verify the validity of neglecting the smoke as conservative. The input model for the NMSF consisted of a system of control volumes, flow pathways, and surfaces sufficient to model the thermal-hydraulic conditions within the facility and the aerosol transport data necessary to simulate the transport of PuO{sub 2} particles. The thermal-hydraulic, heat-transfer, and aerosol-transport models are solved simultaneously with data being exchanged between models. A MELCOR input model was designed such that it would reproduce the salient features of the fire per the corresponding CFAST calculation. Air infiltration into and out of the facility would be affected strongly by wind-driven differential pressures across the building. Therefore, differential pressures were applied to each side of the building according to guidance found in the ASHRAE handbook using a standard-velocity head equation with a leading multiplier to account for the orientation of the wind with the building. The model for the transport of aerosols considered all applicable transport processes, but the deposition within the building clearly was dominated by gravitational settling.

  16. Key Response Planning Factors for the Aftermath of Nuclear Terrorism

    SciTech Connect

    Buddemeier, B R; Dillon, M B

    2009-01-21

    Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

  17. Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine.

    PubMed

    De Mattia, Elena; Cecchin, Erika; Roncato, Rossana; Toffoli, Giuseppe

    2016-09-01

    Great research effort has been focused on elucidating the contribution of host genetic variability on pharmacological outcomes in cancer. Nuclear receptors have emerged as mediators between environmental stimuli and drug pharmacokinetics and pharmacodynamics. The pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors have been reported to regulate transcription of genes that encode drug metabolizing enzymes and transporters. Altered nuclear receptor expression has been shown to affect the metabolism and pharmacological profile of traditional chemotherapeutics and targeted agents. Accordingly, polymorphic variants in these genes have been studied as pharmacogenetic markers of outcome variability. This review summarizes the state of knowledge about the roles played by pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factor expression and genetics as predictive markers of anticancer drug toxicity and efficacy, which can improve cancer precision medicine. PMID:27561454

  18. Pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors as emerging players in cancer precision medicine.

    PubMed

    De Mattia, Elena; Cecchin, Erika; Roncato, Rossana; Toffoli, Giuseppe

    2016-09-01

    Great research effort has been focused on elucidating the contribution of host genetic variability on pharmacological outcomes in cancer. Nuclear receptors have emerged as mediators between environmental stimuli and drug pharmacokinetics and pharmacodynamics. The pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factors have been reported to regulate transcription of genes that encode drug metabolizing enzymes and transporters. Altered nuclear receptor expression has been shown to affect the metabolism and pharmacological profile of traditional chemotherapeutics and targeted agents. Accordingly, polymorphic variants in these genes have been studied as pharmacogenetic markers of outcome variability. This review summarizes the state of knowledge about the roles played by pregnane X receptor, constitutive androstane receptor and hepatocyte nuclear factor expression and genetics as predictive markers of anticancer drug toxicity and efficacy, which can improve cancer precision medicine.

  19. CTCN: Colloid transport code -- nuclear; A user`s manual

    SciTech Connect

    Jain, R.

    1993-09-01

    This report describes the CTCN computer code, designed to solve the equations of transient colloidal transport of radionuclides in porous and fractured media. This Fortran 77 package solves systems of coupled nonlinear differential-algebraic equations with a wide range of boundary conditions. The package uses the Method of Lines technique with a special section which forms finite-difference discretizations in up to four spatial dimensions to automatically convert the system into a set of ordinary differential equations. The CTCN code then solves these equations using a robust, efficient ODE solver. Thus CTCN can be used to solve population balance equations along with the usual transport equations to model colloid transport processes or as a general problem solver to treat up to four-dimensional differential-algebraic systems.

  20. Colloid transport code-nuclear user`s manual

    SciTech Connect

    Jain, R.

    1992-04-03

    This report describes the CTCN computer code, designed to solve the equations of transient colloidal transport of radionuclides in porous and fractured media. This Fortran 77 package solves systems of coupled nonlinear differential equations with a wide range of boundary conditions. The package uses the Method of Lines technique with a special section which forms finite-difference discretizations in up to four spatial dimensions to automatically convert the system into a set of ordinary differential equations. The CTCN code then solves these equations using a robust, efficient ODE solver. Thus CTCN can be used to solve population balance equations along with the usual transport equations to model colloid transport processes or as a general problem solver to treat up to four-dimensional differential systems.

  1. Defective nuclear import of Tpr in Progeria reflects the Ran sensitivity of large cargo transport.

    PubMed

    Snow, Chelsi J; Dar, Ashraf; Dutta, Anindya; Kehlenbach, Ralph H; Paschal, Bryce M

    2013-05-13

    The RanGTPase acts as a master regulator of nucleocytoplasmic transport by controlling assembly and disassembly of nuclear transport complexes. RanGTP is required in the nucleus to release nuclear localization signal (NLS)-containing cargo from import receptors, and, under steady-state conditions, Ran is highly concentrated in the nucleus. We previously showed the nuclear/cytoplasmic Ran distribution is disrupted in Hutchinson-Gilford Progeria syndrome (HGPS) fibroblasts that express the Progerin form of lamin A, causing a major defect in nuclear import of the protein, translocated promoter region (Tpr). In this paper, we show that Tpr import was mediated by the most abundant import receptor, KPNA2, which binds the bipartite NLS in Tpr with nanomolar affinity. Analyses including NLS swapping revealed Progerin did not cause global inhibition of nuclear import. Rather, Progerin inhibited Tpr import because transport of large protein cargoes was sensitive to changes in the Ran nuclear/cytoplasmic distribution that occurred in HGPS. We propose that defective import of large protein complexes with important roles in nuclear function may contribute to disease-associated phenotypes in Progeria.

  2. Approximate penetration factors for nuclear reactions of astrophysical interest

    NASA Technical Reports Server (NTRS)

    Humblet, J.; Fowler, W. A.; Zimmerman, B. A.

    1987-01-01

    The ranges of validity of approximations of P(l), the penetration factor which appears in the parameterization of nuclear-reaction cross sections at low energies and is employed in the extrapolation of laboratory data to even lower energies of astrophysical interest, are investigated analytically. Consideration is given to the WKB approximation, P(l) at the energy of the total barrier, approximations derived from the asymptotic expansion of G(l) for large eta, approximations for small values of the parameter x, applications of P(l) to nuclear reactions, and the dependence of P(l) on channel radius. Numerical results are presented in tables and graphs, and parameter ranges where the danger of serious errors is high are identified.

  3. 77 FR 34194 - Advance Notification to Native American Tribes of Transportation of Certain Types of Nuclear Waste

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... Transportation of Certain Types of Nuclear Waste AGENCY: Nuclear Regulatory Commission. ACTION: Final rule... irradiated reactor fuel and certain nuclear waste passing through or across the boundary of their States... shipment of irradiated reactor fuel and nuclear waste,'' requires licensees to provide advance notice...

  4. Germ Cell Nuclear Factor Regulates Gametogenesis in Developing Gonads

    PubMed Central

    Sabour, Davood; Xu, Xueping; Chung, Arthur C. K.; Le Menuet, Damien; Ko, Kinarm; Tapia, Natalia; Araúzo-Bravo, Marcos J.; Gentile, Luca; Greber, Boris; Hübner, Karin; Sebastiano, Vittorio; Wu, Guangming; Schöler, Hans R.; Cooney, Austin J.

    2014-01-01

    Expression of germ cell nuclear factor (GCNF; Nr6a1), an orphan member of the nuclear receptor gene family of transcription factors, during gastrulation and neurulation is critical for normal embryogenesis in mice. Gcnf represses the expression of the POU-domain transcription factor Oct4 (Pou5f1) during mouse post-implantation development. Although Gcnf expression is not critical for the embryonic segregation of the germ cell lineage, we found that sexually dimorphic expression of Gcnf in germ cells correlates with the expression of pluripotency-associated genes, such as Oct4, Sox2, and Nanog, as well as the early meiotic marker gene Stra8. To elucidate the role of Gcnf during mouse germ cell differentiation, we generated an ex vivo Gcnf-knockdown model in combination with a regulated CreLox mutation of Gcnf. Lack of Gcnf impairs normal spermatogenesis and oogenesis in vivo, as well as the derivation of germ cells from embryonic stem cells (ESCs) in vitro. Inactivation of the Gcnf gene in vivo leads to loss of repression of Oct4 expression in both male and female gonads. PMID:25140725

  5. 10 CFR 70.20a - General license to possess special nuclear material for transport.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... §§ 70.7 (a) through (e), 70.32 (a) and (b), and §§ 70.42, 70.52, 70.55, 70.91, 70.81, 70.82 and 10 CFR... 10 Energy 2 2014-01-01 2014-01-01 false General license to possess special nuclear material for transport. 70.20a Section 70.20a Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING...

  6. 10 CFR 70.20a - General license to possess special nuclear material for transport.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... §§ 70.7 (a) through (e), 70.32 (a) and (b), and §§ 70.42, 70.52, 70.55, 70.91, 70.81, 70.82 and 10 CFR... 10 Energy 2 2010-01-01 2010-01-01 false General license to possess special nuclear material for transport. 70.20a Section 70.20a Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING...

  7. 10 CFR 70.20a - General license to possess special nuclear material for transport.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... §§ 70.7 (a) through (e), 70.32 (a) and (b), and §§ 70.42, 70.52, 70.55, 70.91, 70.81, 70.82 and 10 CFR... 10 Energy 2 2011-01-01 2011-01-01 false General license to possess special nuclear material for transport. 70.20a Section 70.20a Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING...

  8. 10 CFR 70.20a - General license to possess special nuclear material for transport.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... §§ 70.7 (a) through (e), 70.32 (a) and (b), and §§ 70.42, 70.52, 70.55, 70.91, 70.81, 70.82 and 10 CFR... 10 Energy 2 2013-01-01 2013-01-01 false General license to possess special nuclear material for transport. 70.20a Section 70.20a Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING...

  9. 10 CFR 70.20a - General license to possess special nuclear material for transport.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... §§ 70.7 (a) through (e), 70.32 (a) and (b), and §§ 70.42, 70.52, 70.55, 70.91, 70.81, 70.82 and 10 CFR... 10 Energy 2 2012-01-01 2012-01-01 false General license to possess special nuclear material for transport. 70.20a Section 70.20a Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) DOMESTIC LICENSING...

  10. ALARA assessment of spent fuel and nuclear waste transportation systems

    SciTech Connect

    Sutherland, S. H.

    1980-01-01

    The effects of ALARA (as low as reasonably achievable) on transportation system costs were evaluated for LWR spent fuel, high-level commercial and defense wastes, and remotely handled TRU waste. Three dose rate specifications were used: 10 mrem/h at 2m, 5 mrem/h, and 2 mrem/h. The evaluation was done for wastes and LWR spent fuel 1, 3, 5, and 10 years old. Gamma shield materials were depleted uranium, lead, and steel; the neutron shield material was water. Results for a 7-element PWR cask show that uranium shielding is the lightest, and that the increased weight of the low dose rate casks results in 1 to 2 million dollars increase in lifetime transportation costs. 6 figures, 3 tables. (DLC)

  11. Bile acid transporters and regulatory nuclear receptors in the liver and beyond

    PubMed Central

    Halilbasic, Emina; Claudel, Thierry; Trauner, Michael

    2013-01-01

    Summary Bile acid (BA) transporters are critical for maintenance of the enterohepatic BA circulation where BAs exert their multiple physiological functions including stimulation of bile flow, intestinal absorption of lipophilic nutrients, solubilization and excretion of cholesterol, as well as antimicrobial and metabolic effects. Tight regulation of BA transporters via nuclear receptors is necessary to maintain proper BA homeostasis. Hereditary and acquired defects of BA transporters are involved in the pathogenesis of several hepatobiliary disorders including cholestasis, gallstones, fatty liver disease and liver cancer, but also play a role in intestinal and metabolic disorders beyond the liver. Thus, pharmacological modification of BA transporters and their regulatory nuclear receptors opens novel treatment strategies for a wide range of disorders. PMID:22885388

  12. Electrodriven selective transport of Cs+ using chlorinated cobalt dicarbollide in polymer inclusion membrane: a novel approach for cesium removal from simulated nuclear waste solution.

    PubMed

    Chaudhury, Sanhita; Bhattacharyya, Arunasis; Goswami, Asok

    2014-11-01

    The work describes a novel and cleaner approach of electrodriven selective transport of Cs from simulated nuclear waste solutions through cellulose tri acetate (CTA)/poly vinyl chloride (PVC) based polymer inclusion membrane. The electrodriven cation transport together with the use of highly Cs+ selective hexachlorinated derivative of cobalt bis dicarbollide, allows to achieve selective separation of Cs+ from high concentration of Na+ and other fission products in nuclear waste solutions. The transport selectivity has been studied using radiotracer technique as well as atomic emission spectroscopic technique. Transport studies using CTA based membrane have been carried out from neutral solution as well as 0.4 M HNO3, while that with PVC based membrane has been carried out from 3 M HNO3. High decontamination factor for Cs+ over Na+ has been obtained in all the cases. Experiment with simulated high level waste solution shows selective transport of Cs+ from most of other fission products also. Significantly fast Cs+ transport rate along with high selectivity is an interesting feature observed in this membrane. The current efficiency for Cs+ transport has been found to be ∼100%. The promising results show the possibility of using this kind of electrodriven membrane transport methods for nuclear waste treatment.

  13. Study of minimum-weight highway transporters for spent nuclear fuel casks: Technical report

    SciTech Connect

    Hoess, J.A.; Drago, V.J.

    1989-05-01

    There are federal and state limits on the maximum tractor-trailer- payload combination and individual axle loads permissible on US highways. These can generally be considered as two sets, i.e., legal-weight and overweight limits. The number of individual shipments required will decrease as the capacity of the spent nuclear fuel cask increases. Thus, there is an incentive for identifying readily available minimum-weight tractors and trailers capable of safely and reliably transporting as large a cask as possible without exceeding the legal gross combination weight (GCW) of 80,000 lb or selected overweight GCW limit of 110,000 lb. This study identifies options for commercially available heavy-duty on-highway tractors and trailers for transporting proposed future loaded spent nuclear fuel casks. Loaded cask weights of 56,000 and 80,000 lb were selected as reference design points for the legal-weight and overweight transporters, respectively. The technical data on tractor and trailer characteristics obtained indicate that it is possible to develop a tractor-trailer combination, tailored for spent nuclear fuel transportation service, utilizing existing technology and commercially available components, capable of safely and reliably transporting 56,000 and 80,000-lb spent nuclear fuel casks without exceeding GCWs of 80,000 and 10,000 lb, respectively. 4 figs., 14 tabs.

  14. Baculovirus infection of nondividing mammalian cells: mechanisms of entry and nuclear transport of capsids.

    PubMed

    van Loo, N D; Fortunati, E; Ehlert, E; Rabelink, M; Grosveld, F; Scholte, B J

    2001-01-01

    We have studied the infection pathway of Autographa californica multinuclear polyhedrosis virus (baculovirus) in mammalian cells. By titration with a baculovirus containing a green fluorescent protein cassette, we found that several, but not all, mammalian cell types can be infected efficiently. In contrast to previous suggestions, our data show that the asialoglycoprotein receptor is not required for efficient infection. We demonstrate for the first time that this baculovirus can infect nondividing mammalian cells, which implies that the baculovirus is able to transport its genome across the nuclear membrane of mammalian cells. Our data further show that the virus enters via endocytosis, followed by an acid-induced fusion event, which releases the nucleocapsid into the cytoplasm. Cytochalasin D strongly reduces the infection efficiency but not the delivery of nucleocapsids to the cytoplasm, suggesting involvement of actin filaments in cytoplasmic transport of the capsids. Electron microscopic analysis shows the cigar-shaped nucleocapsids located at nuclear pores of nondividing cells. Under these conditions, we observed the viral genome, major capsid protein, and electron-dense capsids inside the nucleus. This suggests that the nucleocapsid is transported through the nuclear pore. This mode of transport seems different from viruses with large spherical capsids, such as herpes simplex virus and adenovirus, which are disassembled before nuclear transport of the genome. The implications for the application of baculovirus or its capsid proteins in gene therapy are discussed.

  15. Calmodulin-dependent nuclear import of HMG-box family nuclear factors: importance of the role of SRY in sex reversal

    PubMed Central

    Kaur, Gurpreet; Delluc-Clavieres, Aurelie; Poon, Ivan K. H.; Forwood, Jade K.; Glover, Dominic J.; Jans, David A.

    2010-01-01

    The HMG (high-mobility group)-box-containing chromatin-remodelling factor SRY (sex-determining region on the Y chromosome) plays a key role in sex determination. Its role in the nucleus is critically dependent on two NLSs (nuclear localization signals) that flank its HMG domain: the C-terminally located ‘β-NLS’ that mediates nuclear transport through Impβ1 (importin β1) and the N-terminally located ‘CaM-NLS’ which is known to recognize the calcium-binding protein CaM (calmodulin). In the present study, we examined a number of missense mutations in the SRY CaM-NLS from human XY sex-reversed females for the first time, showing that they result in significantly reduced nuclear localization of GFP (green fluorescent protein)–SRY fusion proteins in transfected cells compared with wild-type. The CaM antagonist CDZ (calmidazolium chloride) was found to significantly reduce wild-type SRY nuclear accumulation, indicating dependence of SRY nuclear import on CaM. Intriguingly, the CaM-NLS mutants were all resistant to CDZ's effects, implying a loss of interaction with CaM, which was confirmed by direct binding experiments. CaM-binding/resultant nuclear accumulation was the only property of SRY found to be impaired by two of the CaM-NLS mutations, implying that inhibition of CaM-dependent nuclear import is the basis of sex reversal in these cases. Importantly, the CaM-NLS is conserved in other HMG-box-domain-containing proteins such as SOX-2, -9, -10 and HMGN1, all of which were found for the first time to rely on CaM for optimal nuclear localization. CaM-dependent nuclear translocation is thus a common mechanism for this family of important transcription factors. PMID:20528776

  16. Human Factors Considerations in New Nuclear Power Plants: Detailed Analysis.

    SciTech Connect

    OHara,J.; Higgins, J.; Brown, W.; Fink, R.

    2008-02-14

    This Nuclear Regulatory Commission (NRC) sponsored study has identified human-performance issues in new and advanced nuclear power plants. To identify the issues, current industry developments and trends were evaluated in the areas of reactor technology, instrumentation and control technology, human-system integration technology, and human factors engineering (HFE) methods and tools. The issues were organized into seven high-level HFE topic areas: Role of Personnel and Automation, Staffing and Training, Normal Operations Management, Disturbance and Emergency Management, Maintenance and Change Management, Plant Design and Construction, and HFE Methods and Tools. The issues where then prioritized into four categories using a 'Phenomena Identification and Ranking Table' methodology based on evaluations provided by 14 independent subject matter experts. The subject matter experts were knowledgeable in a variety of disciplines. Vendors, utilities, research organizations and regulators all participated. Twenty issues were categorized into the top priority category. This Brookhaven National Laboratory (BNL) technical report provides the detailed methodology, issue analysis, and results. A summary of the results of this study can be found in NUREG/CR-6947. The research performed for this project has identified a large number of human-performance issues for new control stations and new nuclear power plant designs. The information gathered in this project can serve as input to the development of a long-term strategy and plan for addressing human performance in these areas through regulatory research. Addressing human-performance issues will provide the technical basis from which regulatory review guidance can be developed to meet these challenges. The availability of this review guidance will help set clear expectations for how the NRC staff will evaluate new designs, reduce regulatory uncertainty, and provide a well-defined path to new nuclear power plant licensing.

  17. The Exposure Rate Conversion Factor for Nuclear Fallout

    SciTech Connect

    Spriggs, G D

    2009-02-11

    Nuclear fallout is comprised of approximately 2000 radionuclides. About 1000 of these radionuclides are either primary fission products or activated fission products that are created during the burn process. The exposure rate one meter above the surface produced by this complex mixture of radionuclides varies rapidly with time since many of the radionuclides are short-lived and decay numerous times before reaching a stable isotope. As a result, the mixture of radionuclides changes rapidly with time. Using a new code developed at the Lawrence Livermore National Laboratory, the mixture of radionuclides at any given point in time can be calculated. The code also calculates the exposure rate conversion factor (ECF) for all 3864 individual isotopes contained in its database based on the total gamma energy released per decay. Based on the combination of isotope mixture and individual ECFs, the time-dependent variation of the composite exposure rate conversion factor for nuclear fallout can be easily calculated. As example of this new capability, a simple test case corresponding to a 10 kt, uranium-plutonium fuel has been calculated. The results for the time-dependent, composite ECF for this test case are shown in Figure 1. For comparison, we also calculated the composite exposure rate conversion factor using the conversion factors found in Federal Guidance Report No.12 (FGR-12) published by ORNL, which contains the conversion factors for approximately 1000 isotopes. As can be noted from Figure 1, the two functions agree reasonably well at times greater than about 30 minutes. However, they do not agree at early times since FGR-12 does not include all of the short-lived isotopes that are produced in nuclear fallout. It should also be noted that the composite ECF at one hour is 19.7 R/hr per Ci/m{sup 2}. This corresponds to 3148 R/hr per 1 kt per square mile, which agrees reasonably well with the value of 3000 R/hr per 1 kt per square mile as quoted by Glasstone. We have

  18. Nuclear powered Mars cargo transport mission utilizing advanced ion propulsion

    SciTech Connect

    Galecki, D.L.; Patterson, M.J.

    1987-01-01

    Nuclear-powered ion propulsion technology was combined with detailed trajectory analysis to determine propulsion system and trajectory options for an unmanned cargo mission to Mars in support of manned Mars missions. A total of 96 mission scenarios were identified by combining two power levels, two propellants, four values of specific impulse per propellant, three starting altitudes, and two starting velocities. Sixty of these scenarios were selected for a detailed trajectory analysis; a complete propulsion system study was then conducted for 20 of these trajectories. Trip times ranged from 344 days for a xenon propulsion system operating at 300 kW total power and starting from lunar orbit with escape velocity, to 770 days for an argon propulsion system operating at 300 kW total power and starting from nuclear start orbit with circular velocity. Trip times for the 3 MW cases studied ranged from 356 to 413 days. Payload masses ranged from 5700 to 12,300 kg for the 300 kW power level, and from 72,200 to 81,500 kg for the 3 MW power level.

  19. Unified description of equation of state and transport properties of nuclear matter

    SciTech Connect

    Benhar, Omar; Farina, Nicola; Valli, Marco; Fiorilla, Salvatore

    2008-10-13

    Correlated basis function perturbation theory and the formalism of cluster expansions have been recently employed to obtain an effective interaction from a state-of-the-art nucleon nucleon potential model. The approach based on the effective interaction allows for a consistent description of the nuclear matter ground state and nucleon-nucleon scattering in the nuclear medium. This paper reports the the results of numerical calculations of different properties of nuclear and neutron matter, including the equation of state and the shear viscosity and thermal conductivity transport coefficients, carried out using the effective interaction.

  20. Effect of colchicine on mammalian liver nuclear envelope and on nucleo-cytoplasmic RNA transport.

    PubMed

    Agutter, P S; Suckling, K E

    1982-09-27

    The binding of colchicine to nuclear envelopes was studied in order to elucidate the mechanism whereby this compound inhibits nucleocytoplasmic RNA transport. The results suggest that a single class of colchicine-binding site (dissociation constant=approx. 0.7 mM, concentration=approx. 330 nmol colchicine/mg protein) is localised in the nuclear periphery (pore-lamina) and that binding to these sites effects a constriction of the pore-complexes with concomitant inhibition of RNA egress and disordering of the nuclear membrane phospholipid bilayers.

  1. Heat resistant materials and their feasibility issues for a space nuclear transportation system

    SciTech Connect

    Olsen, C.S.

    1991-01-01

    A number of nuclear propulsion concepts based on solid-core nuclear propulsion are being evaluated for a nuclear propulsion transportation system to support the Space Exploration Initiative (SEI) involving the reestablishment of a manned lunar base and the subsequent exploration of Mars. These systems will require high-temperature materials to meet the operating conditions with appropriate reliability and safety built into these systems through the selection and testing of appropriate materials. The application of materials for nuclear thermal propulsion (NTP) and nuclear electric propulsion (NEP) systems and the feasibility issues identified for their use will be discussed. Some mechanical property measurements have been obtained, and compatibility tests were conducted to help identify feasibility issues. 3 refs., 1 fig., 4 tabs.

  2. Model Inspired by Nuclear Pore Complex Suggests Possible Roles for Nuclear Transport Receptors in Determining Its Structure

    PubMed Central

    Osmanović, Dino; Ford, Ian J.; Hoogenboom, Bart W.

    2013-01-01

    Nuclear transport receptors (NTRs) mediate nucleocytoplasmic transport via their affinity for unstructured proteins (polymers) in the nuclear pore complex (NPC). Here, we have modeled the effect of NTRs on polymeric structure in the nanopore confinement of the NPC central conduit. The model explicitly takes into account inter- and intramolecular interactions, as well as the finite size of the NTRs (∼20% of the NPC channel diameter). It reproduces various proposed scenarios for the channel structure, ranging from a central polymer condensate (selective phase) to brushlike polymer arrangements localized at the channel wall (virtual gate, reduction of dimensionality), with the transport receptors lining the polymer surface. In addition, it predicts a new structure in which NTRs become an integral part of the transport barrier by forming a cross-linked network with the unstructured proteins stretching across the pore. The model provides specific and distinctive predictions for the equilibrium spatial distributions of NTRs for these different scenarios that can be experimentally verified by, e.g., superresolution fluorescence microscopy. Moreover, it suggests mechanisms by which globular macromolecules (colloidal particles) can cause polymer-coated nanopores to switch between open and closed configurations, a possible explanation of the biological function of the NPC, and suggests potential technological applications for filtration and single-molecule sensing. PMID:24359750

  3. Criticality Calculations of Fresh LEU and MOX Assemblies for Transport and Storage at the Balakovo Nuclear Power Plant

    SciTech Connect

    Goluoglu, S.

    2001-01-11

    Transportation of low-enriched uranium (LEU) and mixed-oxide (MOX) assemblies to and within the VVER-1000-type Balakovo Nuclear Power Plant is investigated. Effective multiplication factors for fresh fuel assemblies on the railroad platform, fresh fuel assemblies in the fuel transportation vehicle, and fresh fuel assemblies in the spent fuel storage pool are calculated. If there is no absorber between the units, the configurations with all MOX assemblies result in higher effective multiplication factors than the configurations with all LEU assemblies when the system is dry. When the system is flooded, the configurations with all LEU assemblies result in higher effective multiplication factors. For normal operating conditions, effective multiplication factors for all configurations are below the presumed upper subcritical limit of 0.95. For an accident condition of a fully loaded fuel transportation vehicle that is flooded with low-density water (possibly from a fire suppression system), the presumed upper subcritical limit is exceeded by configurations containing LEU assemblies.

  4. Integrated Radiation Transport and Nuclear Fuel Performance for Assembly-Level Simulations

    SciTech Connect

    Clarno, Kevin T; Hamilton, Steven P; Philip, Bobby; Berrill, Mark A; Sampath, Rahul S; Allu, Srikanth; Pugmire, Dave; Dilts, Gary; Banfield, James E

    2012-02-01

    The Advanced Multi-Physics (AMP) Nuclear Fuel Performance code (AMPFuel) is focused on predicting the temperature and strain within a nuclear fuel assembly to evaluate the performance and safety of existing and advanced nuclear fuel bundles within existing and advanced nuclear reactors. AMPFuel was extended to include an integrated nuclear fuel assembly capability for (one-way) coupled radiation transport and nuclear fuel assembly thermo-mechanics. This capability is the initial step toward incorporating an improved predictive nuclear fuel assembly modeling capability to accurately account for source-terms and boundary conditions of traditional (single-pin) nuclear fuel performance simulation, such as the neutron flux distribution, coolant conditions, and assembly mechanical stresses. A novel scheme is introduced for transferring the power distribution from the Scale/Denovo (Denovo) radiation transport code (structured, Cartesian mesh with smeared materials within each cell) to AMPFuel (unstructured, hexagonal mesh with a single material within each cell), allowing the use of a relatively coarse spatial mesh (10 million elements) for the radiation transport and a fine spatial mesh (3.3 billion elements) for thermo-mechanics with very little loss of accuracy. In addition, a new nuclear fuel-specific preconditioner was developed to account for the high aspect ratio of each fuel pin (12 feet axially, but 1 4 inches in diameter) with many individual fuel regions (pellets). With this novel capability, AMPFuel was used to model an entire 17 17 pressurized water reactor fuel assembly with many of the features resolved in three dimensions (for thermo-mechanics and/or neutronics), including the fuel, gap, and cladding of each of the 264 fuel pins; the 25 guide tubes; the top and bottom structural regions; and the upper and lower (neutron) reflector regions. The final, full assembly calculation was executed on Jaguar using 40,000 cores in under 10 hours to model over 162

  5. Interfaces MATXS Cross-Section Libraries to Nuclear Transport Codes for Fusion Systems Analysis.

    1985-04-10

    Version: 00 TRANSX-CTR is a computer code that reads nuclear data from a library in MATXS format and produces transport tables with many discrete-ordinates (Sn) and diffusion codes. Tables can be produced for neutron, photon, or coupled transport. Options include adjoint tables, mixtures, self-shielding, group collapse, homogenization, thermal upscatter, prompt or steady-state fission, transport corrections, elastic removal corrections, and flexible response-function edits. The ability to prepare coupled tables and response edits for heating, damage, gasmore » production, and delayed activity makes TRANSX-CTR especially useful for fusion reactor studies.« less

  6. Roles of hepatocyte nuclear factors in hepatitis B virus infection.

    PubMed

    Kim, Doo Hyun; Kang, Hong Seok; Kim, Kyun-Hwan

    2016-08-21

    Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid). Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process. Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication. Therefore, proper control of HNF function could lead to the inhibition of HBV replication. In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs. This knowledge will enable the identification of new therapeutic targets to cure CHB. PMID:27610013

  7. Roles of hepatocyte nuclear factors in hepatitis B virus infection

    PubMed Central

    Kim, Doo Hyun; Kang, Hong Seok; Kim, Kyun-Hwan

    2016-01-01

    Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid). Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process. Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication. Therefore, proper control of HNF function could lead to the inhibition of HBV replication. In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs. This knowledge will enable the identification of new therapeutic targets to cure CHB. PMID:27610013

  8. Roles of hepatocyte nuclear factors in hepatitis B virus infection

    PubMed Central

    Kim, Doo Hyun; Kang, Hong Seok; Kim, Kyun-Hwan

    2016-01-01

    Approximately 350 million people are estimated to be persistently infected with hepatitis B virus (HBV) worldwide. HBV maintains persistent infection by employing covalently closed circular DNA (cccDNA), a template for all HBV RNAs. Chronic hepatitis B (CHB) patients are currently treated with nucleos(t)ide analogs such as lamivudine, adefovir, entecavir, and tenofovir. However, these treatments rarely cure CHB because they are unable to inhibit cccDNA transcription and inhibit only a late stage in the HBV life cycle (the reverse transcription step in the nucleocapsid). Therefore, an understanding of the factors regulating cccDNA transcription is required to stop this process. Among numerous factors, hepatocyte nuclear factors (HNFs) play the most important roles in cccDNA transcription, especially in the generation of viral genomic RNA, a template for HBV replication. Therefore, proper control of HNF function could lead to the inhibition of HBV replication. In this review, we summarize and discuss the current understanding of the roles of HNFs in the HBV life cycle and the upstream factors that regulate HNFs. This knowledge will enable the identification of new therapeutic targets to cure CHB.

  9. Nuclear reactor heat transport system component low friction support system

    DOEpatents

    Wade, Elman E.

    1980-01-01

    A support column for a heavy component of a liquid metal fast breeder reactor heat transport system which will deflect when the pipes leading coolant to and from the heavy component expand or contract due to temperature changes includes a vertically disposed pipe, the pipe being connected to the heavy component by two longitudinally spaced cycloidal dovetail joints wherein the distal end of each of the dovetails constitutes a part of the surface of a large diameter cylinder and the centerlines of these large diameter cylinders intersect at right angles and the pipe being supported through two longitudinally spaced cycloidal dovetail joints wherein the distal end of each of the dovetails constitutes a part of the surface of a large diameter cylinder and the centerlines of these large diameter cylinders intersect at right angles, each of the cylindrical surfaces bearing on a flat and horizontal surface.

  10. The “Genomic Storm” Induced by Bacterial Endotoxin Is Calmed by a Nuclear Transport Modifier That Attenuates Localized and Systemic Inflammation

    PubMed Central

    Moore, Daniel J.; Wylezinski, Lukasz S.; Hutchens, Martha A.; Hawiger, Jacek

    2014-01-01

    Lipopolysaccharide (LPS) is a potent microbial virulence factor that can trigger production of proinflammatory mediators involved in the pathogenesis of localized and systemic inflammation. Importantly, the role of nuclear transport of stress responsive transcription factors in this LPS-generated “genomic storm” remains largely undefined. We developed a new nuclear transport modifier (NTM) peptide, cell-penetrating cSN50.1, which targets nuclear transport shuttles importin α5 and importin β1, to analyze its effect in LPS-induced localized (acute lung injury) and systemic (lethal endotoxic shock) murine inflammation models. We analyzed a human genome database to match 46 genes that encode cytokines, chemokines and their receptors with transcription factors whose nuclear transport is known to be modulated by NTM. We then tested the effect of cSN50.1 peptide on proinflammatory gene expression in murine bone marrow-derived macrophages stimulated with LPS. This NTM suppressed a proinflammatory transcriptome of 37 out of 84 genes analyzed, without altering expression of housekeeping genes or being cytotoxic. Consistent with gene expression analysis in primary macrophages, plasma levels of 23 out of 26 LPS-induced proinflammatory cytokines, chemokines, and growth factors were significantly attenuated in a murine model of LPS-induced systemic inflammation (lethal endotoxic shock) while the anti-inflammatory cytokine, interleukin 10, was enhanced. This anti-inflammatory reprogramming of the endotoxin-induced genomic response was accompanied by complete protection against lethal endotoxic shock with prophylactic NTM treatment, and 75% protection when NTM was first administered after LPS exposure. In a murine model of localized lung inflammation caused by direct airway exposure to LPS, expression of cytokines and chemokines in the bronchoalveolar space was suppressed with a concomitant reduction of neutrophil trafficking. Thus, calming the LPS-triggered

  11. Cellular stress stimulates nuclear localization signal (NLS) independent nuclear transport of MRJ

    SciTech Connect

    Andrews, Joel F.; Sykora, Landon J.; Barik Letostak, Tiasha; Menezes, Mitchell E.; Mitra, Aparna; Barik, Sailen; Shevde, Lalita A.; Samant, Rajeev S.

    2012-06-10

    HSP40 family member MRJ (DNAJB6) has been in the spot light for its relevance to Huntington's, Parkinson's diseases, limb-girdle muscular dystrophy, placental development, neural stem cells, cell cycle and malignancies such as breast cancer and melanoma. This gene has two spliced variants coding for 2 distinct proteins with significant homology. However, MRJ(L) (large variant) is predominantly localized to the nucleus whereas MRJ(S) (small variant) is predominantly cytoplasmic. Interestingly MRJ(S) translocates to the nucleus in response to heat shock. The classical heat shock proteins respond to crises (stress) by increasing the number of molecules, usually by transcriptional up-regulation. Our studies imply that a quick increase in the molar concentration of MRJ in the nuclear compartment is a novel method by which MRJ responds to stress. We found that MRJ(S) shows NLS (nuclear localization signal) independent nuclear localization in response to heat shock and hypoxia. The specificity of this response is realized due to lack of such response by MRJ(S) when challenged by other stressors, such as some cytokines or UV light. Deletion analysis has allowed us to narrow down on a 20 amino acid stretch at the C-terminal region of MRJ(S) as a potential stress sensing region. Functional studies indicated that constitutive nuclear localization of MRJ(S) promoted attributes of malignancy such as proliferation and invasiveness overall indicating distinct phenotypic characteristics of nuclear MRJ(S).

  12. Integrated Radiation Transport and Nuclear Fuel Performance for Assembly-Level Simulations

    SciTech Connect

    Hamilton, Steven P; Clarno, Kevin T; Philip, Bobby; Berrill, Mark A; Sampath, Rahul S; Allu, Srikanth

    2012-01-01

    The Advanced Multi-Physics (AMP) Nuclear Fuel Performance code (AMPFuel) is focused on predicting the temperature and strain within a nuclear fuel assembly to evaluate the performance and safety of existing and advanced nuclear fuel bundles within existing and advanced nuclear reactors. AMPFuel was extended to include an integrated nuclear fuel assembly capability for (one-way) coupled radiation transport and nuclear fuel assembly thermo-mechanics. This capability is the initial step toward incorporating an improved predictive nuclear fuel assembly modeling capability to accurately account for source-terms, such as neutron flux distribution, coolant conditions and assembly mechanical stresses, of traditional (single-pin) nuclear fuel performance simulation. A novel scheme is introduced for transferring the power distribution from the Scale/Denovo (Denovo) radiation transport code (structured, Cartesian mesh with smeared materials within each cell) to AMPFuel (unstructured, hexagonal mesh with a single material within each cell), allowing the use of a relatively coarse spatial mesh (10 million elements) for the radiation transport and a fine spatial mesh (3.3 billion elements) for thermo-mechanics with very little loss of accuracy. With this novel capability, AMPFuel was used to model an entire 1717 pressurized water reactor fuel assembly with many of the features resolved in three dimensions (for thermo-mechanics and/or neutronics). A full assembly calculation was executed on Jaguar using 40,000 cores in under 10 hours to model over 160 billion degrees of freedom for 10 loading steps. The single radiation transport calculation required about 50% of the time required to solve the thermo-mechanics with a single loading step, which demonstrates that it is feasible to incorporate, in a single code, a high-fidelity radiation transport capability with a high-fidelity nuclear fuel thermo-mechanics capability and anticipate acceptable computational requirements. The

  13. Distinct, but not completely separate spatial transport routes in the nuclear pore complex

    PubMed Central

    2013-01-01

    The nuclear pore complex (NPC), which provides the permeable and selective transport path between the nucleus and cytoplasm of eukaryotic cells, allows both the passive diffusion of small molecules in a signal-independent manner and the transport receptor-facilitated translocation of cargo molecules in a signal-dependent manner. However, the spatial and functional relationships between these two transport pathways, which represent critical information for unraveling the fundamental nucleocytoplasmic transport mechanism, remain in dispute. The direct experimental examination of passive and facilitated transport with a high spatiotemporal resolution under real-time trafficking conditions in native NPCs is still difficult. To address this issue and further define these transport mechanisms, we recently developed single-point edge-excitation sub-diffraction (SPEED) microscopy and a deconvolution algorithm to directly map both passive and facilitated transport routes in three dimensions (3D) in native NPCs. Our findings revealed that passive and facilitated transport occur through spatially distinct transport routes. Signal-independent small molecules exhibit a high probability of passively diffusing through an axial central viscous channel, while transport receptors and their cargo complexes preferentially travel through the periphery, around this central channel, after interacting with phenylalanine-glycine (FG) filaments. Strikingly, these two distinct transport zones are not completely separate either spatially or functionally. Instead, their conformations are closely correlated and simultaneously regulated. In this review, we will specifically highlight a detailed procedure for 3D mapping of passive and facilitated transport routes, demonstrate the correlation between these two distinct pathways, and finally, speculate regarding the regulation of the transport pathways driven by the conformational changes of FG filaments in NPCs. PMID:23669120

  14. Importin {beta}-type nuclear transport receptors have distinct binding affinities for Ran-GTP

    SciTech Connect

    Hahn, Silvia; Schlenstedt, Gabriel

    2011-03-18

    Highlights: {yields} Determination of binding properties of nuclear transport receptor/Ran-GTP complexes. {yields} Biosensor measurements provide constants for dissociation, on-rates, and off-rates. {yields} The affinity of receptors for Ran-GTP is widely divergent. {yields} Dissociation constants differ for three orders of magnitude. {yields} The cellular concentration of yeast Ran is not limiting. -- Abstract: Cargos destined to enter or leave the cell nucleus are typically transported by receptors of the importin {beta} family to pass the nuclear pore complex. The yeast Saccharomyces cerevisiae comprises 14 members of this protein family, which can be divided in importins and exportins. The Ran GTPase regulates the association and dissociation of receptors and cargos as well as the transport direction through the nuclear pore. All receptors bind to Ran exclusively in its GTP-bound state and this event is restricted to the nuclear compartment. We determined the Ran-GTP binding properties of all yeast transport receptors by biosensor measurements and observed that the affinity of importins for Ran-GTP differs significantly. The dissociation constants range from 230 pM to 270 nM, which is mostly based on a variability of the off-rate constants. The divergent affinity of importins for Ran-GTP suggests the existence of a novel mode of nucleocytoplasmic transport regulation. Furthermore, the cellular concentration of {beta}-receptors and of other Ran-binding proteins was determined. We found that the number of {beta}-receptors altogether about equals the amounts of yeast Ran, but Ran-GTP is not limiting in the nucleus. The implications of our results for nucleocytoplasmic transport mechanisms are discussed.

  15. Assessment and requirements of nuclear reaction databases for GCR transport in the atmosphere and structures.

    PubMed

    Cucinotta, F A; Wilson, J W; Shinn, J L; Tripathi, R K

    1998-01-01

    The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) are of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.

  16. Assessment and Requirements of Nuclear Reaction Databases for GCR Transport in the Atmosphere and Structures

    NASA Technical Reports Server (NTRS)

    Cucinotta, F. A.; Wilson, J. W.; Shinn, J. L.; Tripathi, R. K.

    1998-01-01

    The transport properties of galactic cosmic rays (GCR) in the atmosphere, material structures, and human body (self-shielding) am of interest in risk assessment for supersonic and subsonic aircraft and for space travel in low-Earth orbit and on interplanetary missions. Nuclear reactions, such as knockout and fragmentation, present large modifications of particle type and energies of the galactic cosmic rays in penetrating materials. We make an assessment of the current nuclear reaction models and improvements in these model for developing required transport code data bases. A new fragmentation data base (QMSFRG) based on microscopic models is compared to the NUCFRG2 model and implications for shield assessment made using the HZETRN radiation transport code. For deep penetration problems, the build-up of light particles, such as nucleons, light clusters and mesons from nuclear reactions in conjunction with the absorption of the heavy ions, leads to the dominance of the charge Z = 0, 1, and 2 hadrons in the exposures at large penetration depths. Light particles are produced through nuclear or cluster knockout and in evaporation events with characteristically distinct spectra which play unique roles in the build-up of secondary radiation's in shielding. We describe models of light particle production in nucleon and heavy ion induced reactions and make an assessment of the importance of light particle multiplicity and spectral parameters in these exposures.

  17. Radioxenon Production and Transport from an Underground Nuclear Detonation to Ground Surface

    NASA Astrophysics Data System (ADS)

    Sun, Yunwei; Carrigan, Charles R.; Hao, Yue

    2015-02-01

    Radioxenon isotopes are considered as possible indicators for detecting and discriminating underground nuclear explosions. To monitor and sample the release of radioxenon isotopes, both independent and chain-reaction yields need to be considered together with multiphase transport in geological systems from the detonation point to the ground surface. For the sake of simplicity, modeling of radioxenon isotopic radioactivities has typically been focused either on chain reactions in a batch reactor without considering multiphase transport or on radionuclide transport with simplified reactions. Although numerical methods are available for integrating coupled differential equations of complex decay networks, the stiffness of ordinary differential equations due to greatly differing decay rates may require substantial additional effort to obtain solutions for the fully coupled system. For this reason, closed-form solutions for sequential reactions and numerical solutions for multiparent converging and multidaughter branching reactions were previously developed and used to simulate xenon isotopic radioactivities in the batch reactor mode. In this paper, we develop a fully coupled numerical model, which involves tracking 24 components (i.e., 22 radionuclide components plus air and water) in two phases to enhance model predictability of simultaneously simulating xenon isotopic transport and fully coupled chain reactions. To validate the numerical model and verify the corresponding computer code, we derived closed-form solutions for first-order xenon reactions in a batch reactor mode and for single-gas phase transport coupled with the xenon reactions in a one-dimensional column. Finally, cylindrical 3-D simulations of two-phase flow within a dual permeability fracture-matrix medium, simulating the geohydrologic regime of an underground nuclear explosion, indicate the existence of both a strong temporal and spatial dependence of xenon isotopic ratios sampled at the surface. In

  18. Development of a test system for verification and validation of nuclear transport simulations

    SciTech Connect

    White, Morgan C; Triplett, Brian S; Anghaie, Samim

    2008-01-01

    Verification and validation of nuclear data is critical to the accuracy of both stochastic and deterministic particle transport codes. In order to effectively test a set of nuclear data, the data must be applied to a wide variety of transport problems. Performing this task in a timely, efficient manner is tedious. The nuclear data team at Los Alamos National laboratory in collaboration with the University of Florida has developed a methodology to automate the process of nuclear data verification and validation (V and V). This automated V and V process can efficiently test a number of data libraries using well defined benchmark experiments, such as those in the International Criticality Safety Benchmark Experiment Project (ICSBEP). The process is implemented through an integrated set of Pyton scripts. Material and geometry data are read from an existing medium or given directly by the user to generate a benchmark experiment template file. The user specifies the choice of benchmark templates, codes, and libraries to form a V and V project. The Python scripts generate input decks for multiple transport codes from the templates, run and monitor individual jobs, and parse the relevant output automatically. The output can then be used to generate reports directly or can be stored into a database for later analysis. This methodology eases the burden on the user by reducing the amount of time and effort required for obtaining and compiling calculation results. The resource savings by using this automated methodology could potentially be an enabling technology for more sophisticated data studies, such as nuclear data uncertainty quantification. Once deployed, this tool will allow the nuclear data community to more thoroughly test data libraries leading to higher fidelity data in the future.

  19. Nuclear factor-kappa B links carcinogenic and chemopreventive agents.

    PubMed

    Ralhan, Ranju; Pandey, Manoj K; Aggarwal, Bharat B

    2009-01-01

    Cancer prevention requires avoidance of tobacco, alcohol, high-fat diet, polluted air and water, sedentary lifestyle, and of mechanical, physical, psychological, or chemical stress. How these factors can cause cancer, is suggested by the transcription nuclear factor-kappa B (NF-kappa B), that is activated by tobacco, alcohol, high-fat diet, environment pollutants, cancer-causing viruses (human papillomavirus, hepatitis B and C viruses, HIV) and bacteria (Helicobacter pylori), ultraviolet light, ionizing radiation, obesity, and stress. Furthermore, NF-kappa B-regulated gene products have been implicated in transformation of cells, and in proliferation, survival, invasion, angiogenesis, and metastasis. Suppression of NF-kappa B activation by the phytochemicals present in fruits and vegetables provides the molecular basis for their ability to prevent cancer. Other agents identified from spices and Ayurvedic and traditional Chinese medicines also been found to suppress NF-kappa B activation and thus may have potential for cancer prevention. The classic chemopreventive agent should offer long-term safety, low cost, and efficacy. The current review discuses in detail numerous agents such as curcumin, resveratrol, silymarin, catechins and others as potential chemopreventive agents. Thus, cancer, an ancient problem, may have an ancient solution. PMID:19482682

  20. Molecular Architecture of the Transport Channel of the Nuclear Pore Complex

    SciTech Connect

    Solmaz, Sozanne R.; Chauhan, Radha; Blobel, Günter; Mel; #269; ák, Ivo

    2012-05-22

    The nuclear pore complex encloses a central channel for nucleocytoplasmic transport, which is thought to consist of three nucleoporins, Nup54, Nup58, and Nup62. However, the structure and composition of the channel are elusive. We determined the crystal structures of the interacting domains between these nucleoporins and pieced together the molecular architecture of the mammalian transport channel. Located in the channel midplane is a flexible Nup54Nup58 ring that can undergo large rearrangements yielding diameter changes from {approx}20 to {approx}40 nm. Nup62Nup54 triple helices project alternately up and down from either side of the midplane ring and form nucleoplasmic and cytoplasmic entries. The channel consists of as many as 224 copies of the three nucleoporins, amounting to a molar mass of 12.3 MDa and contributing 256 phenylalanine-glycine repeat regions. We propose that the occupancy of these repeat regions with transport receptors modulates ring diameter and transport activity.

  1. BRIEF REPORT: Pair production from nuclear collisions and cosmic ray transport

    NASA Astrophysics Data System (ADS)

    Norbury, John W.

    2006-09-01

    Modern cosmic ray transport codes, that are capable of use for a variety of applications, need to include all significant atomic, nuclear and particle reactions at a variety of energies. Lepton pair production from nucleus nucleus collisions has not been included in transport codes to date. Using the methods of Baur, Bertulani and Baron, the present report provides estimates of electron positron pair production cross sections for nuclei and energies relevant to cosmic ray transport. It is shown that the cross sections are large compared to other typical processes such as single neutron removal due to strong or electromagnetic interactions. Therefore, lepton pair production may need to be included in some transport code applications involving MeV electrons.

  2. Land and Water Use, CO2 Emissions, and Worker Radiological Exposure Factors for the Nuclear Fuel Cycle

    SciTech Connect

    Brett W Carlsen; Brent W Dixon; Urairisa Pathanapirom; Eric Schneider; Bethany L. Smith; Timothy M. AUlt; Allen G. Croff; Steven L. Krahn

    2013-08-01

    The Department of Energy Office of Nuclear Energy’s Fuel Cycle Technologies program is preparing to evaluate several proposed nuclear fuel cycle options to help guide and prioritize Fuel Cycle Technology research and development. Metrics are being developed to assess performance against nine evaluation criteria that will be used to assess relevant impacts resulting from all phases of the fuel cycle. This report focuses on four specific environmental metrics. • land use • water use • CO2 emissions • radiological Dose to workers Impacts associated with the processes in the front-end of the nuclear fuel cycle, mining through enrichment and deconversion of DUF6 are summarized from FCRD-FCO-2012-000124, Revision 1. Impact estimates are developed within this report for the remaining phases of the nuclear fuel cycle. These phases include fuel fabrication, reactor construction and operations, fuel reprocessing, and storage, transport, and disposal of associated used fuel and radioactive wastes. Impact estimates for each of the phases of the nuclear fuel cycle are given as impact factors normalized per unit process throughput or output. These impact factors can then be re-scaled against the appropriate mass flows to provide estimates for a wide range of potential fuel cycles. A companion report, FCRD-FCO-2013-000213, applies the impact factors to estimate and provide a comparative evaluation of 40 fuel cycles under consideration relative to these four environmental metrics.

  3. RISKIND: A computer program for calculating radiological consequences and health risks from transportation of spent nuclear fuel

    SciTech Connect

    Yuan, Y.C.; Chen, S.Y.; Biwer, B.M.; LePoire, D.J.

    1995-11-01

    This report presents the technical details of RISKIND, a computer code designed to estimate potential radiological consequences and health risks to individuals and the collective population from exposures associated with the transportation of spent nuclear fuel. RISKIND is a user-friendly, interactive program that can be run on an IBM or equivalent personal computer under the Windows{trademark} environment. Several models are included in RISKIND that have been tailored to calculate the exposure to individuals under various incident-free and accident conditions. The incident-free models assess exposures from both gamma and neutron radiation and can account for different cask designs. The accident models include accidental release, atmospheric transport, and the environmental pathways of radionuclides from spent fuels; these models also assess health risks to individuals and the collective population. The models are supported by databases that are specific to spent nuclear fuels and include a radionuclide inventory and dose conversion factors. In addition, the flexibility of the models allows them to be used for assessing any accidental release involving radioactive materials. The RISKIND code allows for user-specified accident scenarios as well as receptor locations under various exposure conditions, thereby facilitating the estimation of radiological consequences and health risks for individuals. Median (50% probability) and typical worst-case (less than 5% probability of being exceeded) doses and health consequences from potential accidental releases can be calculated by constructing a cumulative dose/probability distribution curve for a complete matrix of site joint-wind-frequency data. These consequence results, together with the estimated probability of the entire spectrum of potential accidents, form a comprehensive, probabilistic risk assessment of a spent nuclear fuel transportation accident.

  4. The Pseudorabies Virus DNA Polymerase Accessory Subunit UL42 Directs Nuclear Transport of the Holoenzyme.

    PubMed

    Wang, Yi-Ping; Du, Wen-Juan; Huang, Li-Ping; Wei, Yan-Wu; Wu, Hong-Li; Feng, Li; Liu, Chang-Ming

    2016-01-01

    Pseudorabies virus (PRV) DNA replication occurs in the nuclei of infected cells and requires the viral DNA polymerase. The PRV DNA polymerase comprises a catalytic subunit, UL30, and an accessory subunit, UL42, that confers processivity to the enzyme. Its nuclear localization is a prerequisite for its enzymatic function in the initiation of viral DNA replication. However, the mechanisms by which the PRV DNA polymerase holoenzyme enters the nucleus have not been determined. In this study, we characterized the nuclear import pathways of the PRV DNA polymerase catalytic and accessory subunits. Immunofluorescence analysis showed that UL42 localizes independently in the nucleus, whereas UL30 alone predominantly localizes in the cytoplasm. Intriguingly, the localization of UL30 was completely shifted to the nucleus when it was coexpressed with UL42, demonstrating that nuclear transport of UL30 occurs in an UL42-dependent manner. Deletion analysis and site-directed mutagenesis of the two proteins showed that UL42 contains a functional and transferable bipartite nuclear localization signal (NLS) at amino acids 354-370 and that K(354), R(355), and K(367) are important for the NLS function, whereas UL30 has no NLS. Coimmunoprecipitation assays verified that UL42 interacts with importins α3 and α4 through its NLS. In vitro nuclear import assays demonstrated that nuclear accumulation of UL42 is a temperature- and energy-dependent process and requires both importins α and β, confirming that UL42 utilizes the importin α/β-mediated pathway for nuclear entry. In an UL42 NLS-null mutant, the UL42/UL30 heterodimer was completely confined to the cytoplasm when UL42 was coexpressed with UL30, indicating that UL30 utilizes the NLS function of UL42 for its translocation into the nucleus. Collectively, these findings suggest that UL42 contains an importin α/β-mediated bipartite NLS that transports the viral DNA polymerase holoenzyme into the nucleus in an in vitro expression

  5. Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65

    PubMed Central

    Snow, Wanda M.; Pahlavan, Payam S.; Djordjevic, Jelena; McAllister, Danielle; Platt, Eric E.; Alashmali, Shoug; Bernstein, Michael J.; Suh, Miyoung; Albensi, Benedict C.

    2015-01-01

    Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory. PMID:26635523

  6. Morris Water Maze Training in Mice Elevates Hippocampal Levels of Transcription Factors Nuclear Factor (Erythroid-derived 2)-like 2 and Nuclear Factor Kappa B p65.

    PubMed

    Snow, Wanda M; Pahlavan, Payam S; Djordjevic, Jelena; McAllister, Danielle; Platt, Eric E; Alashmali, Shoug; Bernstein, Michael J; Suh, Miyoung; Albensi, Benedict C

    2015-01-01

    Research has identified several transcription factors that regulate activity-dependent plasticity and memory, with cAMP-response element binding protein (CREB) being the most well-studied. In neurons, CREB activation is influenced by the transcription factor nuclear factor kappa B (NF-κB), considered central to immunity but more recently implicated in memory. The transcription factor early growth response-2 (Egr-2), an NF-κB gene target, is also associated with learning and memory. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), an antioxidant transcription factor linked to NF-κB in pathological conditions, has not been studied in normal memory. Given that numerous transcription factors implicated in activity-dependent plasticity demonstrate connections to NF-κB, this study simultaneously evaluated protein levels of NF-κB, CREB, Egr-2, Nrf2, and actin in hippocampi from young (1 month-old) weanling CD1 mice after training in the Morris water maze, a hippocampal-dependent spatial memory task. After a 6-day acquisition period, time to locate the hidden platform decreased in the Morris water maze. Mice spent more time in the target vs. non-target quadrants of the maze, suggestive of recall of the platform location. Western blot data revealed a decrease in NF-κB p50 protein after training relative to controls, whereas NF-κB p65, Nrf2 and actin increased. Nrf2 levels were correlated with platform crosses in nearly all tested animals. These data demonstrate that training in a spatial memory task results in alterations in and associations with particular transcription factors in the hippocampus, including upregulation of NF-κB p65 and Nrf2. Training-induced increases in actin protein levels caution against its use as a loading control in immunoblot studies examining activity-dependent plasticity, learning, and memory.

  7. Thermodynamics of competitive molecular channel transport: application to artificial nuclear pores.

    PubMed

    Bauer, Wolfgang R; Nadler, Walter

    2010-12-13

    In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probability when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules.

  8. Thermodynamics of Competitive Molecular Channel Transport: Application to Artificial Nuclear Pores

    PubMed Central

    Bauer, Wolfgang R.; Nadler, Walter

    2010-01-01

    In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probablity when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules. PMID:21179205

  9. Transportation issues in nuclear medicine and the release of radioactivity into the environment.

    PubMed

    Westerman, B R

    1986-07-01

    Large volumes of radioactive materials are shipped daily over the nation's highways, by air, and by other transportation modes for a variety of purposes. These shipments include those intended for nuclear medicine applications. Shipments are governed by the Federal Department of Transportation, the Nuclear Regulatory Commission, and, for international shipments, the International Atomic Energy Agency. Knowledge of the regulations of these agencies is essential for maintenance of a viable radiation safety program. The use of radioactive materials is invariably accompanied by the potential for release of radioactivity into the environment. This potential is addressed in the recommendations and regulations of several voluntary and governmental agencies. Recently, new concepts have been introduced into these recommendations and regulations that use the concepts of "annual limit of intake," "committed effective dose equivalent," and "derived air concentrations." These concepts improve the applicability of present standards for the release of radioactive materials into the environment and for the protection of individuals from these materials. PMID:3749916

  10. Spent Nuclear Fuel Transportation: An Examination of Potential Lessons Learned From Prior Shipping Campaigns

    SciTech Connect

    Marsha Keister; Kathryn McBride

    2006-08-01

    The Nuclear Waste Policy Act of 1982 (NWPA), as amended, assigned the Department of Energy (DOE) responsibility for developing and managing a Federal system for the disposal of spent nuclear fuel (SNF) and high-level radioactive waste (HLW). The Office of Civilian Radioactive Waste Management (OCRWM) is responsible for accepting, transporting, and disposing of SNF and HLW at the Yucca Mountain repository in a manner that protects public health, safety, and the environment; enhances national and energy security; and merits public confidence. OCRWM faces a near-term challenge—to develop and demonstrate a transportation system that will sustain safe and efficient shipments of SNF and HLW to a repository. To better inform and improve its current planning, OCRWM has extensively reviewed plans and other documents related to past high-visibility shipping campaigns of SNF and other radioactive materials within the United States. This report summarizes the results of this review and, where appropriate, lessons learned.

  11. Full-Scale Accident Testing in Support of Used Nuclear Fuel Transportation.

    SciTech Connect

    Durbin, Samuel G.; Lindgren, Eric R.; Rechard, Rob P.; Sorenson, Ken B.

    2014-09-01

    The safe transport of spent nuclear fuel and high-level radioactive waste is an important aspect of the waste management system of the United States. The Nuclear Regulatory Commission (NRC) currently certifies spent nuclear fuel rail cask designs based primarily on numerical modeling of hypothetical accident conditions augmented with some small scale testing. However, NRC initiated a Package Performance Study (PPS) in 2001 to examine the response of full-scale rail casks in extreme transportation accidents. The objectives of PPS were to demonstrate the safety of transportation casks and to provide high-fidelity data for validating the modeling. Although work on the PPS eventually stopped, the Blue Ribbon Commission on America’s Nuclear Future recommended in 2012 that the test plans be re-examined. This recommendation was in recognition of substantial public feedback calling for a full-scale severe accident test of a rail cask to verify evaluations by NRC, which find that risk from the transport of spent fuel in certified casks is extremely low. This report, which serves as the re-assessment, provides a summary of the history of the PPS planning, identifies the objectives and technical issues that drove the scope of the PPS, and presents a possible path for moving forward in planning to conduct a full-scale cask test. Because full-scale testing is expensive, the value of such testing on public perceptions and public acceptance is important. Consequently, the path forward starts with a public perception component followed by two additional components: accident simulation and first responder training. The proposed path forward presents a series of study options with several points where the package performance study could be redirected if warranted.

  12. The Use of Transportable Processing Systems for the Treatment of Radioactive Nuclear Wastes

    SciTech Connect

    Phillips, Ch.; Houghton, D.; Crawford, G.

    2008-07-01

    EnergySolutions has developed two major types of radioactive processing plants based on its experience in the USA and UK, and its exclusive North American access to the intellectual property and know-how developed over 50 years at the Sellafield nuclear site in the UK. Passive Secure Cells are a type of hot cell used in place of the Canyons typically used in US-designed radioactive facilities. They are used in permanent, large scale plants suitable for long term processing of large amounts of radioactive material. The more recently developed Transportable Processing Systems, which are the subject of this paper, are used for nuclear waste processing and clean-up when processing is expected to be complete within shorter timescales and when it is advantageous to be able to move the processing equipment amongst a series of geographically spread-out waste treatment sites. Such transportable systems avoid the construction of a monolithic waste processing plant which itself would require extensive decommissioning and clean-up when its mission is complete. This paper describes a range of transportable radioactive waste processing equipment that EnergySolutions and its partners have developed including: the portable MOSS drum-based waste grouting system, the skid mounted MILWPP large container waste grouting system, the IPAN skid-mounted waste fissile content non-destructive assay system, the Wiped Film Evaporator low liquid hold-up transportable evaporator system, the CCPU transportable solvent extraction cesium separation system, and the SEP mobile shielded cells for emptying radioactive debris from water-filled silos. Maximum use is made of proven, robust, and compact processing equipment such as centrifugal contactors, remote sampling systems, and cement grout feed and metering devices. Flexible, elastomer-based Hose-in-Hose assemblies and container-based transportable pump booster stations are used in conjunction with these transportable waste processing units for

  13. Nuclear waste transportation: case studies of identifying stakeholder risk information needs.

    PubMed

    Drew, Christina H; Grace, Deirdre A; Silbernagel, Susan M; Hemmings, Erin S; Smith, Alan; Griffith, William C; Takaro, Timothy K; Faustman, Elaine M

    2003-03-01

    The U.S. Department of Energy (DOE) is responsible for the cleanup of our nation's nuclear legacy, involving complex decisions about how and where to dispose of nuclear waste and how to transport it to its ultimate disposal site. It is widely recognized that a broad range of stakeholders and tribes should be involved in this kind of decision. All too frequently, however, stakeholders and tribes are only invited to participate by commenting on processes and activities that are near completion; they are not included in the problem formulation stages. Moreover, it is often assumed that high levels of complexity and uncertainty prevent meaningful participation by these groups. Considering the types of information that stakeholders and tribes need to be able to participate in the full life cycle of decision making is critical for improving participation and transparency of decision making. Toward this objective, the Consortium for Risk Evaluation with Stakeholder Participation (CRESP) participated in three public processes relating to nuclear waste transportation and disposal in 1997-1998. First, CRESP organized focus groups to identify concerns about nuclear waste transportation. Second, CRESP conducted exit surveys at regional public workshops held by DOE to get input from stakeholders on intersite waste transfer issues. Third, CRESP developed visual tools to synthesize technical information and allow stakeholders and tribes with varying levels of knowledge about nuclear waste to participate in meaningful discussion. In this article we share the results of the CRESP findings, discuss common themes arising from these interactions, and comment on special considerations needed to facilitate stakeholder and tribal participation in similar decision-making processes.

  14. Advanced Intermediate Heat Transport Loop Design Configurations for Hydrogen Production Using High Temperature Nuclear Reactors

    SciTech Connect

    Chang Oh; Cliff Davis; Rober Barner; Paul Pickard

    2005-11-01

    The US Department of Energy is investigating the use of high-temperature nuclear reactors to produce hydrogen using either thermochemical cycles or high-temperature electrolysis. Although the hydrogen production processes are in an early stage of development, coupling either of these processes to the high-temperature reactor requires both efficient heat transfer and adequate separation of the facilities to assure that off-normal events in the production facility do not impact the nuclear power plant. An intermediate heat transport loop will be required to separate the operations and safety functions of the nuclear and hydrogen plants. A next generation high-temperature reactor could be envisioned as a single-purpose facility that produces hydrogen or a dual-purpose facility that produces hydrogen and electricity. Early plants, such as the proposed Next Generation Nuclear Plant (NGNP), may be dual-purpose facilities that demonstrate both hydrogen and efficient electrical generation. Later plants could be single-purpose facilities. At this stage of development, both single- and dual-purpose facilities need to be understood. A number of possible configurations for a system that transfers heat between the nuclear reactor and the hydrogen and/or electrical generation plants were identified. These configurations included both direct and indirect cycles for the production of electricity. Both helium and liquid salts were considered as the working fluid in the intermediate heat transport loop. Methods were developed to perform thermal-hydraulic evaluations and cycle-efficiency evaluations of the different configurations and coolants. The thermal-hydraulic evaluations estimated the sizes of various components in the intermediate heat transport loop for the different configurations. The relative sizes of components provide a relative indication of the capital cost associated with the various configurations. Estimates of the overall cycle efficiency of the various

  15. Nuclear waste transportation: case studies of identifying stakeholder risk information needs.

    PubMed Central

    Drew, Christina H; Grace, Deirdre A; Silbernagel, Susan M; Hemmings, Erin S; Smith, Alan; Griffith, William C; Takaro, Timothy K; Faustman, Elaine M

    2003-01-01

    The U.S. Department of Energy (DOE) is responsible for the cleanup of our nation's nuclear legacy, involving complex decisions about how and where to dispose of nuclear waste and how to transport it to its ultimate disposal site. It is widely recognized that a broad range of stakeholders and tribes should be involved in this kind of decision. All too frequently, however, stakeholders and tribes are only invited to participate by commenting on processes and activities that are near completion; they are not included in the problem formulation stages. Moreover, it is often assumed that high levels of complexity and uncertainty prevent meaningful participation by these groups. Considering the types of information that stakeholders and tribes need to be able to participate in the full life cycle of decision making is critical for improving participation and transparency of decision making. Toward this objective, the Consortium for Risk Evaluation with Stakeholder Participation (CRESP) participated in three public processes relating to nuclear waste transportation and disposal in 1997-1998. First, CRESP organized focus groups to identify concerns about nuclear waste transportation. Second, CRESP conducted exit surveys at regional public workshops held by DOE to get input from stakeholders on intersite waste transfer issues. Third, CRESP developed visual tools to synthesize technical information and allow stakeholders and tribes with varying levels of knowledge about nuclear waste to participate in meaningful discussion. In this article we share the results of the CRESP findings, discuss common themes arising from these interactions, and comment on special considerations needed to facilitate stakeholder and tribal participation in similar decision-making processes. PMID:12611653

  16. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity.

    PubMed

    Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun; Wang, Wei; Liu, Jing; Liu, Wei; Pan, Shaokun; Xie, Youhua

    2016-09-16

    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 for 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.

  17. Nuclear factor Y regulates ancient budgerigar hepadnavirus core promoter activity.

    PubMed

    Shen, Zhongliang; Liu, Yanfeng; Luo, Mengjun; Wang, Wei; Liu, Jing; Liu, Wei; Pan, Shaokun; Xie, Youhua

    2016-09-16

    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 for 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. PMID:27501758

  18. Hepatocyte nuclear factor 1β controls nephron tubular development.

    PubMed

    Massa, Filippo; Garbay, Serge; Bouvier, Raymonde; Sugitani, Yoshinobu; Noda, Tetsuo; Gubler, Marie-Claire; Heidet, Laurence; Pontoglio, Marco; Fischer, Evelyne

    2013-02-01

    Nephron morphogenesis is a complex process that generates blood-filtration units (glomeruli) connected to extremely long and patterned tubular structures. Hepatocyte nuclear factor 1β (HNF1β) is a divergent homeobox transcription factor that is expressed in kidney from the first steps of nephrogenesis. Mutations in HNF1B (OMIM #137920) are frequently found in patients with developmental renal pathologies, the mechanisms of which have not been completely elucidated. Here we show that inactivation of Hnf1b in the murine metanephric mesenchyme leads to a drastic tubular defect characterized by the absence of proximal, distal and Henle's loop segments. Nephrons were eventually characterized by glomeruli, with a dilated urinary space, directly connected to collecting ducts via a primitive and short tubule. In the absence of HNF1β early nephron precursors gave rise to deformed S-shaped bodies characterized by the absence of the typical bulge of epithelial cells at the bend between the mid and lower segments. The lack of this bulge eventually led to the absence of proximal tubules and Henle's loops. The expression of several genes, including Irx1, Osr2 and Pou3f3, was downregulated in the S-shaped bodies. We also observed decreased expression of Dll1 and the consequent defective activation of Notch in the prospective tubular compartment of comma- and S-shaped bodies. Our results reveal a novel hierarchical relationship between HNF1β and key genes involved in renal development. In addition, these studies define a novel structural and functional component of S-shaped bodies at the origin of tubule formation.

  19. Dynamic mitochondrial localization of nuclear transcription factor HMGA1

    SciTech Connect

    Dement, Gregory A.; Treff, Nathan R.; Magnuson, Nancy S.; Franceschi, Vincent; Reeves, Raymond . E-mail: reevesr@mail.wsu.edu

    2005-07-15

    It has been well established that high mobility group A1 (HMGA1) proteins act within the nucleus of mammalian cells as architectural transcription factors that regulate the expression of numerous genes. Here, however, we report on the unexpected cytoplasmic/mitochondrial localization of the HMGA1 proteins within multiple cell types. Indirect immunofluorescence, electron microscopic immunolocalization, and Western blot studies revealed that, in addition to the nucleus, HMGA1 proteins could also be found in both the cytoplasm and mitochondria of randomly dividing populations of wild-type murine NIH3T3 cells and transgenic human MCF-7 breast cancer epithelial cells expressing a hemagglutinin tagged-HMGA1a fusion protein. While the molecular mechanisms underlying these novel subcellular localization patterns have not yet been determined, initial synchronization studies revealed a dynamic, cell cycle-dependent translocation of HMGA1 proteins from the nucleus into the cytoplasm and mitochondria of NIH3T3 cells. Furthermore, preliminary functionality studies utilizing a modified 'chromatin' immunoprecipitation protocol revealed that HMGA1 retains its DNA binding capabilities within the mitochondria and associates with the regulatory D-loop region in vivo. We discuss potential new biological roles for the classically nuclear HMGA1 proteins with regard to the observed nucleocytoplasmic translocation, mitochondrial internalization, and regulatory D-loop DNA binding.

  20. Nuclear factor-kappa B signaling in skeletal muscle atrophy.

    PubMed

    Li, Hong; Malhotra, Shweta; Kumar, Ashok

    2008-10-01

    Skeletal muscle atrophy/wasting is a serious complication of a wide range of diseases and conditions such as aging, disuse, AIDS, chronic obstructive pulmonary disease, space travel, muscular dystrophy, chronic heart failure, sepsis, and cancer. Emerging evidence suggests that nuclear factor-kappa B (NF-kappaB) is one of the most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-kappaB in skeletal muscle leads to degradation of specific muscle proteins, induces inflammation and fibrosis, and blocks the regeneration of myofibers after injury/atrophy. Recent studies employing genetic mouse models have provided strong evidence that NF-kappaB can serve as an important molecular target for the prevention of skeletal muscle loss. In this article, we have outlined the current understanding regarding the role of NF-kappaB in skeletal muscle with particular reference to different models of muscle wasting and the development of novel therapy.

  1. Evaluation of groundwater flow and transport at the Shoal underground nuclear test: An interim report

    SciTech Connect

    Pohll, G.; Chapman, J.; Hassan, A.; Papelis, C.; Andricevic, R.; Shirley, C.

    1998-07-01

    Since 1962, all United States nuclear tests have been conducted underground. A consequence of this testing has been the deposition of large amounts of radioactive materials in the subsurface, sometimes in direct contact with groundwater. The majority of this testing occurred on the Nevada Test Site, but a limited number of experiments were conducted in other locations. One of these is the subject of this report, the Project Shoal Area (PSA), located about 50 km southeast of Fallon, Nevada. The Shoal test consisted of a 12-kiloton-yield nuclear detonation which occurred on October 26, 1963. Project Shoal was part of studies to enhance seismic detection of underground nuclear tests, in particular, in active earthquake areas. Characterization of groundwater contamination at the Project Shoal Area is being conducted by the US Department of Energy (DOE) under the Federal Facility Agreement and Consent Order (FFACO) with the State of Nevada Department of Environmental Protection and the US Department of Defense (DOD). This order prescribes a Corrective Action Strategy (Appendix VI), which, as applied to underground nuclear tests, involves preparing a Corrective Action Investigation Plan (CAIP), Corrective Action Decision Document (CADD), Corrective Action Plan, and Closure Report. The scope of the CAIP is flow and transport modeling to establish contaminant boundaries that are protective of human health and the environment. This interim report describes the current status of the flow and transport modeling for the PSA.

  2. A Preliminary Evaluation of Using Fill Materials to Stabilize Used Nuclear Fuel During Storage and Transportation

    SciTech Connect

    Maheras, Steven J.; Best, Ralph; Ross, Steven B.; Lahti, Erik A.; Richmond, David J.

    2012-08-01

    This report contains a preliminary evaluation of potential fill materials that could be used to fill void spaces in and around used nuclear fuel contained in dry storage canisters in order to stabilize the geometry and mechanical structure of the used nuclear fuel during extended storage and transportation after extended storage. Previous work is summarized, conceptual descriptions of how canisters might be filled were developed, and requirements for potential fill materials were developed. Elements of the requirements included criticality avoidance, heat transfer or thermodynamic properties, homogeneity and rheological properties, retrievability, material availability and cost, weight and radiation shielding, and operational considerations. Potential fill materials were grouped into 5 categories and their properties, advantages, disadvantages, and requirements for future testing were discussed. The categories were molten materials, which included molten metals and paraffin; particulates and beads; resins; foams; and grout. Based on this analysis, further development of fill materials to stabilize used nuclear fuel during storage and transportation is not recommended unless options such as showing that the fuel remains intact or canning of used nuclear fuel do not prove to be feasible.

  3. Regulation of serotonin transporter gene expression in human glial cells by growth factors.

    PubMed

    Kubota, N; Kiuchi, Y; Nemoto, M; Oyamada, H; Ohno, M; Funahashi, H; Shioda, S; Oguchi, K

    2001-04-01

    The aims of this study were to identify monoamine transporters expressed in human glial cells, and to examine the regulation of their expression by stress-related growth factors. The expression of serotonin transporter mRNA was detected by reverse transcriptase-polymerase chain reaction in normal human astrocytes, whereas the dopamine transporter (DAT) and the norepinephrine transporter (NET) were not detected. The cDNA sequence of the "glial" serotonin transporter in astrocytes was consistent with that reported for the "neuronal" serotonin transporter (SERT). Moreover, we also demonstrated SERT expression in glial fibrillary acidic protein-positive cells by immunocytochemical staining in normal human astrocytes. Serotonin transporter gene expression was also detected in glioma-derived cell lines (A172, KG-1-C and KGK). Addition of basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF) for 2 days increased serotonin transporter gene expression in astrocytes and JAR (human choriocarcinoma cell line). Basic fibroblast growth factor, but not epidermal growth factor, increased specific [3H]serotonin uptake in astrocytes in a time (1-4 days)- and concentration (20-100 ng/ml)-dependent manner. The expression of genes for basic fibroblast growth factor and epidermal growth factor receptors was detected in astrocytes. These findings suggest that the expression of the serotonin transporter in human glial cells is positively regulated by basic fibroblast growth factor. PMID:11301061

  4. [Influence of work factors on health state in personnel servicing military nuclear technical objects].

    PubMed

    Poluboiarinov, V N; Iusov, I G; Ivanchenko, A V; Turlakov, Iu S

    2014-01-01

    Complex of occupational studies and medical, statistical research helped to reveal climate, geographic and other factors influencing health state of personnel servicing military nuclear technical objects. Considering peculiarities of occupational activities in various specialists, the authors specified measures to improve medical service for nuclear technical military officers directly working with nuclear ammunition. Practical application of the measures helped to gain 1.5-1.7 times improvement in morbidity parameters among nuclear technical military officers. PMID:25069272

  5. Potential Role of Nuclear Factor κB in Diabetic Cardiomyopathy

    PubMed Central

    Lorenzo, O.; Picatoste, B.; Ares-Carrasco, S.; Ramírez, E.; Egido, J.; Tuñón, J.

    2011-01-01

    Diabetic cardiomyopathy entails the cardiac injury induced by diabetes independently of any vascular disease or hypertension. Some transcription factors have been proposed to control the gene program involved in the setting and development of related processes. Nuclear factor-kappa B is a pleiotropic transcription factor associated to the regulation of many heart diseases. However, the nuclear factor-kappa B role in diabetic cardiomyopathy is under investigation. In this paper, we review the nuclear factor-kappa B pathway and its role in several processes that have been linked to diabetic cardiomyopathy, such as oxidative stress, inflammation, endothelial dysfunction, fibrosis, hypertrophy and apoptosis. PMID:21772665

  6. Assessment of hydrologic transport of radionuclides from the Rulison Underground Nuclear Test Site, Colorado

    SciTech Connect

    Earman, S.; Chapman, J.; Andricevic, R.

    1996-09-01

    The U.S. Department of Energy (DOE) is operating an environmental restoration program to characterize, remediate, and close non-Nevada Test Site locations that were used for nuclear testing. Evaluation of radionuclide transport by groundwater from these sites is an important part of the preliminary risk analysis. These evaluations are undertaken to allow prioritization of the test areas in terms of risk, provide a quantitative basis for discussions with regulators and the public about future work at the sites, and provide a framework for assessing data needs to be filled by site characterization. The Rulison site in west-central Colorado was the location of an underground detonation of a 40-kiloton nuclear device in 1969. The test took place 2,568 m below ground surface in the Mesaverde Formation. Though located below the regional water table, none of the bedrock formations at the site yielded water during hydraulic tests, indicating extremely low permeability conditions. The scenario evaluated was the migration of radionuclides from the blast-created cavity through the Mesaverde Formation. Transport calculations were performed using the solute flux method, with input based on the limited data available for the site. Model results suggest that radionuclides from the test are contained entirely within the area currently administered by DOE. The transport calculations are most sensitive to changes in the mean groundwater velocity and the correlation scale of hydraulic conductivity, with transport of strontium and cesium also sensitive to the sorption coefficient.

  7. Multiphase, multicomponent flow and transport models for Nuclear Test-Ban Treaty monitoring and nuclear waste disposal applications

    NASA Astrophysics Data System (ADS)

    Jordan, Amy

    Open challenges remain in using numerical models of subsurface flow and transport systems to make useful predictions related to nuclear waste storage and nonproliferation. The work presented here addresses the sensitivity of model results to unknown parameters, states, and processes, particularly uncertainties related to incorporating previously unrepresented processes (e.g., explosion-induced fracturing, hydrous mineral dehydration) into a subsurface flow and transport numerical simulator. The Finite Element Heat and Mass (FEHM) transfer code is used for all numerical models in this research. An experimental campaign intended to validate the predictive capability of numerical models that include the strongly coupled thermal, hydrological, and chemical processes in bedded salt is also presented. Underground nuclear explosions (UNEs) produce radionuclide gases that may seep to the surface over weeks to months. The estimated timing of gas arrival at the surface may be used to deploy personnel and equipment to the site of a suspected UNE, if allowed under the terms of the Comprehensive Nuclear Test-Ban Treaty. A model was developed using FEHM that considers barometrically pumped gas transport through a simplified fractured medium and was used to quantify the impact of uncertainties in hydrologic parameters (fracture aperture, matrix permeability, porosity, and saturation) and season of detonation on the timing of gas breakthrough. Numerical sensitivity analyses were performed for the case of a 1 kt UNE at a 400 m burial depth. Gas arrival time was found to be most affected by matrix permeability and fracture aperture. Gases having higher diffusivity were more sensitive to uncertainty in the rock properties. The effect of seasonality in the barometric pressure forcing was found to be important, with detonations in March the least likely to be detectable based on barometric data for Rainier Mesa, Nevada. Monte Carlo modeling was also used to predict the window of

  8. New approach to creation of geometrical module for nuclear reactor neutron transport computer simulation analysis

    SciTech Connect

    Poveschenko, T.; Poveschenko, O.

    2012-07-01

    This paper presents the new approach to creation of geometrical module for nuclear reactor neutron transport computer simulation analysis so called the differential cross method. It is elaborated for detecting boards between physical zones. It is proposed to use GMSH open source mesh editor extended by some features: a special option and a special kind of mesh (cubic background mesh).This method is aimed into Monte Carlo Method as well as for deterministic neutron transport methods. Special attention is attended for reactor core composed of a set of material zones with complicate geometrical boundaries. The idea of this approach is described. In general case method works for 3-D space. Algorithm of creation of the geometrical module is given. 2-D neutron transport benchmark-test for RBMK reactor cluster cell is described. It demonstrates the ability of this approach to provide flexible definition of geometrical meshing with preservation of curved surface or any level of heterogeneity. (authors)

  9. Single-Molecule Imaging to Characterize the Transport Mechanism of the Nuclear Pore Complex.

    PubMed

    Jeremy, Grace; Stevens, James; Lowe, Alan R

    2016-01-01

    In the eukaryotic cell, a large macromolecular channel, known as the Nuclear Pore Complex (NPC), mediates all molecular transport between the nucleus and cytoplasm. In recent years, single-molecule fluorescence (SMF) imaging has emerged as a powerful tool to study the molecular mechanism of transport through the NPC. More recently, techniques such as single-molecule localization microscopy (SMLM) have enabled the spatial and temporal distribution of cargos, transport receptors and even structural components of the NPC to be determined with nanometre accuracy. In this protocol, we describe a method to study the position and/or motion of individual molecules transiting through the NPC with high spatial and temporal precision. PMID:27283299

  10. Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions.

    PubMed

    Nefiodov, A V; Plunien, G; Soff, G

    2002-08-19

    The influence of nuclear polarization on the bound-electron g factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron g factor in highly charged ions.

  11. Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions.

    PubMed

    Nefiodov, A V; Plunien, G; Soff, G

    2002-08-19

    The influence of nuclear polarization on the bound-electron g factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron g factor in highly charged ions. PMID:12190457

  12. Assessment of hydrologic transport of radionuclides from the Rio Blanco underground nuclear test site, Colorado

    SciTech Connect

    Chapman, J.; Earman, S.; Andricevic, R.

    1996-10-01

    DOE is operating an environmental restoration program to characterize, remediate, and close non-Nevada Test Site locations used for nuclear testing. Evaluation of radionuclide transport by groundwater is part of preliminary risk analysis. These evaluations allow prioritization of test areas in terms of risk, provide a basis for discussions with regulators and the public about future work, and provide a framework for assessing site characterization data needs. The Rio Blanco site in Colorado was the location of the simultaneous detonation of three 30-kiloton nuclear devices. The devices were located 1780, 1899, and 2039 below ground surface in the Fort Union and Mesaverde formations. Although all the bedrock formations at the site are thought to contain water, those below the Green River Formation (below 1000 in depth) are also gas-bearing, and have very low permeabilities. The transport scenario evaluated was the migration of radionuclides from the blast-created cavity through the Fort Union Formation. Transport calculations were performed using the solute flux method, with input based on the limited data available for the site. Model results suggest that radionuclides from the test are contained entirely within the area currently administered by DOE. This modeling was performed to investigate how the uncertainty in various physical parameters affect radionuclide transport at the site, and to serve as a starting point for discussion regarding further investigation; it was not intended to be a definitive simulation of migration pathways or radionuclide concentration values. Given the sparse data, the modeling results may differ significantly from reality. Confidence in transport predictions can be increased by obtaining more site data, including the amount of radionuclides which would have been available for transport (i.e., not trapped in melt glass or vented during gas flow testing), and the hydraulic properties of the formation. 38 refs., 6 figs., 1 tab.

  13. DOS-HEATING6: A general conduction code with nuclear heat generation derived from DOT-IV transport calculations

    SciTech Connect

    Williams, M.L.; Yuecel, A.; Nadkarny, S.

    1988-05-01

    The HEATING6 heat conduction code is modified to (a) read the multigroup particle fluxes from a two-dimensional DOT-IV neutron- photon transport calculation, (b) interpolate the fluxes from the DOT-IV variable (optional) mesh to the HEATING6 control volume mesh, and (c) fold the interpolated fluxes with kerma factors to obtain a nuclear heating source for the heat conduction equation. The modified HEATING6 is placed as a module in the ORNL discrete ordinates system (DOS), and has been renamed DOS-HEATING6. DOS-HEATING6 provides the capability for determining temperature distributions due to nuclear heating in complex, multi-dimensional systems. All of the original capabilities of HEATING6 are retained for the nuclear heating calculation; e.g., generalized boundary conditions (convective, radiative, finned, fixed temperature or heat flux), temperature and space dependent thermal properties, steady-state or transient analysis, general geometry description, etc. The numerical techniques used in the code are reviewed and the user input instructions and JCL to perform DOS-HEATING6 calculations are presented. Finally a sample problem involving coupled DOT-IV and DOS-HEATING6 calculations of a complex space-reactor configurations described, and the input and output of the calculations are listed. 10 refs., 11 figs., 6 tabs.

  14. Characterization of a baculovirus nuclear localization signal domain in the late expression factor 3 protein

    SciTech Connect

    Au, Victoria; Yu Mei; Carstens, Eric B.

    2009-03-01

    The baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) single-stranded DNA binding protein LEF-3 is a multi-functional protein that is required to transport the helicase protein P143 into the nucleus of infected cells where they function to replicate viral DNA. The N-terminal 56 amino acid region of LEF-3 is required for nuclear transport. In this report, we analyzed the effect of site-specific mutagenesis of LEF-3 on its intracellular distribution. Fluorescence microscopy of expression plasmid-transfected cells demonstrated that the residues 28 to 32 formed the core nuclear localization signal, but other adjacent positively-charged residues augmented these sequences. Comparison with other group I Alphabaculoviruses suggested that this core region functionally duplicated residues including 18 and 19. This was demonstrated by the loss of nuclear localization when the equivalent residues (18 to 20) in Choristoneura fumiferana nucleopolyhedrovirus (CfMNPV) LEF-3 were mutated. The AcMNPV LEF-3 nuclear localization domain was also shown to drive nuclear transport in mammalian cells indicating that the protein nuclear import systems in insect and mammalian cells are conserved. We also demonstrated by mutagenesis that two conserved cysteine residues located at 82 and 106 were not essential for nuclear localization or for interaction with P143. However, by using a modified construct of P143 that localized on its own to the nucleus, we demonstrated that a functional nuclear localization domain on LEF-3 was required for interaction between LEF-3 and P143.

  15. Structural and functional analysis of Hikeshi, a new nuclear transport receptor of Hsp70s.

    PubMed

    Song, Jinsue; Kose, Shingo; Watanabe, Ai; Son, Se Young; Choi, Saehae; Hong, Hyerim; Yamashita, Eiki; Park, Il Yeong; Imamoto, Naoko; Lee, Soo Jae

    2015-03-01

    Hikeshi is a nuclear transport receptor required for cell survival after stress. It mediates heat-shock-induced nuclear import of 70 kDa heat-shock proteins (Hsp70s) through interactions with FG-nucleoporins (FG-Nups), which are proteins in nuclear pore complexes (NPCs). Here, the crystal structure of human Hikeshi is presented at 1.8 Å resolution. Hikeshi forms an asymmetric homodimer that is responsible for the interaction with Hsp70s. The asymmetry of Hikeshi arises from the distinct conformation of the C-terminal domain (CTD) and the flexibility of the linker regions of each monomer. Structure-guided mutational analyses showed that both the flexible linker region and the CTD are important for nuclear import of Hsp70. Pull-down assays revealed that only full-length Hsp70s can interact with Hikeshi. The N-terminal domain (NTD) consists of a jelly-roll/β-sandwich fold structure which contains hydrophobic pockets involved in FG-Nup recognition. A unique extended loop (E-loop) in the NTD is likely to regulate the interactions of Hikeshi with FG-Nups. The crystal structure of Hikeshi explains how Hikeshi participates in the regulation of nuclear import through the recognition of FG-Nups and which part of Hikeshi affects its binding to Hsp70. This study is the first to yield structural insight into this highly unique import receptor.

  16. The Security of Russia's Nuclear Arsenal: The Human Factor

    SciTech Connect

    Ball, D.Y.

    1999-10-12

    Assertions by the Russian military that all of their nuclear weapons are secure against theft and that nuclear units within the military are somehow insulated from the problems plaguing the Russian military should not be accepted uncritically. Accordingly, we should not give unwarranted credence to the pronouncements of military figures like Cal.-Gen. Igor Valynkin, Chief of the Defense Ministry's 12th Main Directorate, which oversees the country's nuclear arsenal. He contends that ''Russian nuclear weapons are under reliable supervision'' and that ''talk about the unreliability of our control over nuclear weapons has only one pragmatic goal--to convince international society that the country is incapable of maintaining nuclear safety and to introduce international oversight over those weapons, as it is done, for example, in Iraq.'' While the comparison to Iraq is preposterous, many analysts might agree with Valynkin's sanguine appraisal of the security of Russia's nuclear weapons. In contrast, I argue that the numerous difficulties confronting the military as a whole should cause concern in the West over the security of the Russian nuclear arsenal.

  17. Hepatocyte nuclear factor-4 prevents silencing of hepatocyte nuclear factor-1 expression in hepatoma x fibroblast cell hybrids.

    PubMed Central

    Bulla, G A

    1997-01-01

    Hepatocyte nuclear factors-1alpha (HNF1alpha) and -4 (HNF4) are components of a liver-enriched transcription activation pathway which is thought to play a critical role in hepatocyte-specific gene expression, including activation of alpha1-antitrypsin gene expression. HNF1alpha, HNF4 and alpha1-antitrypsin (alpha1AT) genes are extinguished in hepatoma/fibroblast somatic cell hybrids, suggesting that fibroblasts contain a repressor-like activity. To determine the molecular basis for silencing of these genes in cell hybrids, ectopic expression of HNF1alpha and HNF4 was used. Results show that constitutive expression of HNF4 prevents extinction of HNF1alpha gene expression in hepatoma/fibroblast hybrids. In contrast, forced HNF1alpha expression failed to prevent extinction of the HNF4 locus in cell hybrids. Likewise, the alpha1AT gene remained silent in the presence of both HNF1alpha and HNF4. These results suggest that extinction of HNF1alpha is a simple lack-of-activation phenotype, whereas extinction of HNF4 andalpha1AT loci is more complex, perhaps involving negative regulation. PMID:9171105

  18. Effects of transportation of spent nuclear fuel on repository SNF performance

    SciTech Connect

    Quinn, Robert

    2007-07-01

    Available in abstract form only. Full text of publication follows: Spent nuclear fuel (SNF) destined for emplacement in a repository must be transported to the repository. Most worldwide experience with SNF transportation has been with low burnup SNF, Further, since much of the transported SNF was destined for reprocessing, the integrity of the fuel upon arrival was only a minimal concern. For repository emplacement, the long term performance of many of the barriers is crucial to the analytical predictions of overall performance of the repository over the long time spans which must be considered. As a result, the condition of the SNF after transportation is very important. This evaluation looks at the issues associated with SNF performance in a repository, specifically issues associated with high burnup fuel and transportation effects on cladding conditions. The issues associated with high-burnup fuels include hydride formation and post-irradiation temperatures that can lead to hydrogen embrittlement and hydride reorientation which can affect cladding integrity performance. Issues associated with effects of post-irradiation discharge wet and dry storage of SNF and effects on transportation as they relate to the integrity of the SNF cladding materials include the effects of potential oxidation of the fuel, as well as effects of transportation conditions due to vibration. The evaluation also considers how such issues, and the ability to address them, may be affected by the US DOE canister-based repository design approach. Experience in licensing SNF for transportation will be cited in developing suggestions for addressing these issues, and possible future activities which may be needed to further to address these issues will be identified. (author)

  19. GLE2, a Saccharomyces cerevisiae homologue of the Schizosaccharomyces pombe export factor RAE1, is required for nuclear pore complex structure and function.

    PubMed Central

    Murphy, R; Watkins, J L; Wente, S R

    1996-01-01

    To identify and characterize novel factors required for nuclear transport, a genetic screen was conducted in the yeast Saccharomyces cerevisiae. Mutations that were lethal in combination with a null allele of the gene encoding the nucleoporin Nup100p were isolated using a colony-sectoring assay. Three complementation groups of gle (for GLFG lethal) mutants were identified. In this report, the characterization of GLE2 is detailed. GLE2 encodes a 40.5-kDa polypeptide with striking similarity to that of Schizosaccharomyces pombe RAE1. In indirect immunofluorescence and nuclear pore complex fractionation experiments, Gle2p was associated with nuclear pore complexes. Mutated alleles of GLE2 displayed blockage of polyadenylated RNA export; however, nuclear protein import was not apparently diminished. Immunofluorescence and thin-section electron microscopic analysis revealed that the nuclear pore complex and nuclear envelope structure was grossly perturbed in gle2 mutants. Because the clusters of herniated pore complexes appeared subsequent to the export block, the structural perturbations were likely indirect consequences of the export phenotype. Interestingly, a two-hybrid interaction was detected between Gle2p and Srp1p, the nuclear localization signal receptor, as well as Rip1p, a nuclear export signal-interacting protein. We propose that Gle2p has a novel role in mediating nuclear transport. Images PMID:8970155

  20. {beta}-Catenin can act as a nuclear import receptor for its partner transcription factor, lymphocyte enhancer factor-1 (lef-1)

    SciTech Connect

    Asally, Munehiro; Yoneda, Yoshihiro . E-mail: yyoneda@anat3.med.osaka-u.ac.jp

    2005-08-15

    Nuclear accumulation of {beta}-catenin plays an important role in the Wnt signaling pathway. In the nucleus, {beta}-catenin acts as a transcriptional co-activator for TCF/LEF family of transcription factors. It has been shown that lef-1 contains a typical basic type nuclear localization signal (NLS) and is transported into the nucleus by the conventional import pathway. In this study, we found that a mutant lef-1 lacking the classical NLS accumulated in the nucleus of living cells, when {beta}-catenin was co-expressed. In addition, in a cell-free import assay, lef-1 migrated into the nucleus in the presence of {beta}-catenin alone without any other soluble factors. In contrast, another mutant lef-1 lacking the {beta}-catenin binding domain failed to migrate into the nucleus, even in the presence of {beta}-catenin. These findings indicate that {beta}-catenin alone can mediate the nuclear import of lef-1 through the direct binding. Collectively, we propose that there are two distinct pathways for the nuclear import of lef-1: importin {alpha}/{beta}-mediated and {beta}-catenin-mediated one, which provides a novel paradigm for Wnt signaling pathway.

  1. Anomalous Solute Transport in Saturated Porous Media: Linking Transport Model Parameters to Electrical and Nuclear Magnetic Resonance Properties

    NASA Astrophysics Data System (ADS)

    Swanson, R. D.; Binley, A. M.; Keating, K.; France, S.; Osterman, G. K.; Day-Lewis, F. D.; Singha, K.

    2013-12-01

    The advection-dispersion equation fails to describe non-Fickian solute transport in saturated porous media, necessitating the use of other models. The dual-domain mass transfer (DDMT) model partitions the total porosity into mobile and less-mobile domains with solute exchange between the domains; consequently, the DDMT model can produce a better fit to breakthrough curves (BTCs) in systems defined by more- and less-mobile components. However, direct experimental estimation of DDMT model parameters such as rate of exchange and the mobile and less-mobile porosities remains elusive. Consequently, model parameters are often calculated purely as a model fitting exercise. There is a clear need for material characterization techniques that can offer some insight into the pore space geometrical arrangement, particularly if such techniques can be extended to the field scale. Here, we interpret static direct-current (DC) resistivity, complex resistivity (CR) and nuclear magnetic resonance (NMR) geophysical measurements in the characterization of mass transfer parameters. We use two different samples of the zeolite clinoptilolite, a material shown to demonstrate solute mass transfer due to a significant intragranular porosity, along with glass beads as a control. We explore the relation between geophysical and DDMT parameters in conjunction with supporting material characterization methods. Our results reveal how these geophysical measurements can offer some insight into the pore structures controlling the observed anomalous transport behavior.

  2. Multiphase, multicomponent flow and transport models for Nuclear Test-Ban Treaty monitoring and nuclear waste disposal applications

    NASA Astrophysics Data System (ADS)

    Jordan, Amy

    Open challenges remain in using numerical models of subsurface flow and transport systems to make useful predictions related to nuclear waste storage and nonproliferation. The work presented here addresses the sensitivity of model results to unknown parameters, states, and processes, particularly uncertainties related to incorporating previously unrepresented processes (e.g., explosion-induced fracturing, hydrous mineral dehydration) into a subsurface flow and transport numerical simulator. The Finite Element Heat and Mass (FEHM) transfer code is used for all numerical models in this research. An experimental campaign intended to validate the predictive capability of numerical models that include the strongly coupled thermal, hydrological, and chemical processes in bedded salt is also presented. Underground nuclear explosions (UNEs) produce radionuclide gases that may seep to the surface over weeks to months. The estimated timing of gas arrival at the surface may be used to deploy personnel and equipment to the site of a suspected UNE, if allowed under the terms of the Comprehensive Nuclear Test-Ban Treaty. A model was developed using FEHM that considers barometrically pumped gas transport through a simplified fractured medium and was used to quantify the impact of uncertainties in hydrologic parameters (fracture aperture, matrix permeability, porosity, and saturation) and season of detonation on the timing of gas breakthrough. Numerical sensitivity analyses were performed for the case of a 1 kt UNE at a 400 m burial depth. Gas arrival time was found to be most affected by matrix permeability and fracture aperture. Gases having higher diffusivity were more sensitive to uncertainty in the rock properties. The effect of seasonality in the barometric pressure forcing was found to be important, with detonations in March the least likely to be detectable based on barometric data for Rainier Mesa, Nevada. Monte Carlo modeling was also used to predict the window of

  3. [Medical and hygienic aspects of instrumental supervision system over nuclear materials and radioactive substances transport on Russian Federation territory].

    PubMed

    Grabskiĭ, Iu V; Gavrish, N N; Shevchenko, G T; Viaz'min, S O; Pertsev, V S; Kirillov, V F; Tsov'ianov, A G

    2014-01-01

    Hygienic evaluation of radiation situation in operation of mobile and stationery elements within a project of national system for instrumental supervision over nuclear materials and radioactive substances transport, created with a Global initiative against nuclear terrorism. Levels of exposure to ionizing radiation of the screening complexes appeared to match requirements on radiation safety for service personnel and general population.

  4. CHARACTERISTICS OF NEXT-GENERATION SPENT NUCLEAR FUEL (SNF) TRANSPORT AND STORAGE CASKS

    SciTech Connect

    Haire, M.J.; Forsberg, C.W.; Matveev, V.Z.; Shapovalov, V.I.

    2004-10-03

    The design of spent nuclear fuel (SNF) casks used in the present SNF disposition systems has evolved from early concepts about the nuclear fuel cycle. The reality today is much different from that envisioned by early nuclear scientists. Most SNF is placed in pool storage, awaiting reprocessing (as in Russia) or disposal at a geologic SNF repository (as in the United States). Very little transport of SNF occurs. This paper examines the requirements for SNF casks from today's perspective and attempts to answer this question: What type of SNF cask would be produced if we were to start over and design SNF casks based on today's requirements? The characteristics for a next-generation SNF cask system are examined and are found to be essentially the same in Russia and the United States. It appears that the new depleted uranium dioxide (DUO2)-steel cermet material will enable these requirements to be met. Depleted uranium (DU) is uranium in which a portion of the 235U isotope has been removed during a uranium enrichment process. The DUO2-steel cermet material is described. The United States and Russia are cooperating toward the development of a next-generation, dual-purpose, storage and transport SNF system.

  5. Plasticity of an ultrafast interaction between nucleoporins and nuclear transport receptors.

    PubMed

    Milles, Sigrid; Mercadante, Davide; Aramburu, Iker Valle; Jensen, Malene Ringkjøbing; Banterle, Niccolò; Koehler, Christine; Tyagi, Swati; Clarke, Jane; Shammas, Sarah L; Blackledge, Martin; Gräter, Frauke; Lemke, Edward A

    2015-10-22

    The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, and nuclear magnetic resonance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with near diffusion-limited on rates, as shown by stopped-flow kinetic measurements. This is achieved using multiple, minimalistic, low-affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. We propose that these exceptional physical characteristics enable a rapid and specific transport mechanism in the physiological context, a notion supported by single molecule in-cell assays on intact NPCs.

  6. Plasticity of an Ultrafast Interaction between Nucleoporins and Nuclear Transport Receptors

    PubMed Central

    Milles, Sigrid; Mercadante, Davide; Aramburu, Iker Valle; Jensen, Malene Ringkjøbing; Banterle, Niccolò; Koehler, Christine; Tyagi, Swati; Clarke, Jane; Shammas, Sarah L.; Blackledge, Martin; Gräter, Frauke; Lemke, Edward A.

    2015-01-01

    Summary The mechanisms by which intrinsically disordered proteins engage in rapid and highly selective binding is a subject of considerable interest and represents a central paradigm to nuclear pore complex (NPC) function, where nuclear transport receptors (NTRs) move through the NPC by binding disordered phenylalanine-glycine-rich nucleoporins (FG-Nups). Combining single-molecule fluorescence, molecular simulations, and nuclear magnetic resonance, we show that a rapidly fluctuating FG-Nup populates an ensemble of conformations that are prone to bind NTRs with near diffusion-limited on rates, as shown by stopped-flow kinetic measurements. This is achieved using multiple, minimalistic, low-affinity binding motifs that are in rapid exchange when engaging with the NTR, allowing the FG-Nup to maintain an unexpectedly high plasticity in its bound state. We propose that these exceptional physical characteristics enable a rapid and specific transport mechanism in the physiological context, a notion supported by single molecule in-cell assays on intact NPCs. PMID:26456112

  7. Categorisation of nuclear explosions from legitimate radioxenon sources with atmospheric transport modelling

    NASA Astrophysics Data System (ADS)

    Schoeppner, M.; Postelt, F.; Kalinowski, M.; Plastino, W.

    2012-04-01

    Radioxenon is produced during nuclear explosions and due to its high fission ratio during the reaction and its noble gas character the isotopes can be detected remote from the location of the explosion. Therefore it is used by the Comprehensive Nuclear-Test-Ban Organization (CTBTO) as an indicator for the nuclear character of an explosion and is monitored with the International Monitoring System (IMS). The concentration of radioxenon in the air is continuously measured by multiple stations worldwide and is in need of an automatic categorization scheme in order to highlight signals of interest and to sort out signals that can be explained by legitimate sources. The dispersion and transport of radioxenon emissions through the atmosphere can be simulated with atmospheric transport modelling. Many legitimate sources of radioxenon exist: Nuclear power plants and isotope production facilities are mainly responsible for the worldwide background. The characterisation of this background is an important prerequisite to discriminate nuclear explosion signals against the background. It has been discovered that the few existing isotope production facilities are the major contributors to the background, each with emission strengths in the order of magnitude or more than all nuclear power plants together. Therefore, especially the characterization of these few, but strong, emitters can improve the quality of the signal prediction. Since the location of such an emitter is usually known the source-receptor sensitivity matrices can be utilized together with measured radioxenon concentrations from IMS stations in order to deduct information about the time dependent emissions from the strong emitter. An automatic method to determine an approximated, time dependent source term of an emitter with known location has been developed and is presented. This is a potentially valid tool for the categorization of radioxenon samples, because it can be used to assess whether the measured

  8. Environmental Baseline File: National Transportation

    SciTech Connect

    1999-05-22

    This Environmental Baseline File summarizes and consolidates information related to the national-level transportation of commercial spent nuclear fuel. Topics address include: shipmnents of commercial spent nuclear fuel based on mostly truck and mostly rail shipping scenarios; transportation routing for commercial spent nuclear fuel sites and DOE sites; radionuclide inventories for various shipping container capacities; transportation routing; populations along transportation routes; urbanized area population densities; the impacts of historical, reasonably foreseeable, and general transportation; state-level food transfer factors; Federal Guidance Report No. 11 and 12 radionuclide dose conversion factors; and national average atmospheric conditions.

  9. Nuclear fact book

    SciTech Connect

    Hill, O. F.; Platt, A. M.; Robinson, J. V.

    1983-05-01

    This reference provides significant highlights and summary facts in the following areas: general energy; nuclear energy; nuclear fuel cycle; uranium supply and enrichment; nuclear reactors; spent fuel and advanced repacking concepts; reprocessing; high-level waste; gaseous waste; transuranic waste; low-level waste; remedial action; transportation; disposal; radiation information; environment; legislation; socio-political aspects; conversion factors; and a glossary. (GHT)

  10. Propanil inhibits tumor necrosis factor-alpha production by reducing nuclear levels of the transcription factor nuclear factor-kappab in the macrophage cell line ic-21.

    PubMed

    Frost, L L; Neeley, Y X; Schafer, R; Gibson, L F; Barnett, J B

    2001-05-01

    Tumor necrosis factor-alpha (TNF-alpha) is an essential proinflammatory cytokine whose production is normally stimulated by bacterial cell wall components, such as lipopolysaccharide (LPS), during an infection. Macrophages stimulated with LPS in vitro produce several cytokines, including TNF-alpha. LPS-stimulated primary mouse macrophages produced less TNF-alpha protein and message after treatment with the herbicide propanil (Xie et al., Toxicol. Appl. Pharmacol. 145, 184-191, 1997). Nuclear factor-kappaB (NF-kappaB) tightly regulates TNF-alpha transcription. Therefore, as a step toward understanding the mechanism of the effect of propanil on TNF-alpha transcription, IC-21 cells were transfected with a TNF-alpha promoter-luciferase construct, and the effect of propanil on luciferase activity was measured. Cells transfected with promoter constructs containing a kappaB site showed decreased luciferase activity relative to controls after propanil treatment. These observations implicated NF-kappaB binding as an intracellular target of propanil. Further studies demonstrated a marked reduction in the nuclear levels of the stimulatory p65 subunit of NF-kappaB after propanil treatment, as measured by fluorescence confocal microscopy and Western blot analysis. The p50 subunit of NF-kappaB was not found to be reduced after propanil exposure by Western blot. Electrophoretic mobility gel shift assays showed decreased DNA binding of both p65/p50 heterodimers and p50/p50 homodimers to the kappaB3 site of the TNF-alpha promoter of propanil-treated cells. The marked reduction in nuclear p65/p50 NF-kappaB levels and diminished binding to the TNF-alpha promoter in propanil-treated cells are consistent with reduced TNF-alpha levels induced by LPS. PMID:11312646

  11. Analysis of the risk of transporting spent nuclear fuel by train

    SciTech Connect

    Elder, H.K.

    1981-09-01

    This report uses risk analyses to analyze the safety of transporting spent nuclear fuel for commercial rail shipping systems. The rail systems analyzed are those expected to be used in the United States when the total electricity-generating capacity by nuclear reactors is 100 GW in the late 1980s. Risk as used in this report is the product of the probability of a release of material to the environment and the consequences resulting from the release. The analysis includes risks in terms of expected fatalities from release of radioactive materials due to transportation accidents involving PWR spent fuel shipped in rail casks. The expected total risk from such shipments is 1.3 x 10/sup -4/ fatalities per year. Risk spectrums are developed for shipments of spent fuel that are 180 days and 4 years out-of-reactor. The risk from transporting spent fuel by train is much less (by 2 to 4 orders of magnitude) than the risk to society from other man-caused events such as dam failure.

  12. Nuclear Factor of Activated T Cells Transcription Factor Nfatp Controls Superantigen-Induced Lethal Shock

    PubMed Central

    Tsytsykova, Alla V.; Goldfeld, Anne E.

    2000-01-01

    Tumor necrosis factor α (TNF-α) is the key mediator of superantigen-induced T cell lethal shock. Here, we show that nuclear factor of activated T cells transcription factor, NFATp, controls susceptibility to superantigen-induced lethal shock in mice through its activation of TNF-α gene transcription. In NFATp-deficient mice, T cell stimulation leads to delayed induction and attenuation of TNF-α mRNA levels, decreased TNF-α serum levels, and resistance to superantigen-induced lethal shock. By contrast, after lipopolysaccharide (LPS) challenge, serum levels of TNF-α and susceptibility to shock are unaffected. These results demonstrate that NFATp is an essential activator of immediate early TNF-α gene expression in T cells and they present in vivo evidence of the inducer- and cell type–specific regulation of TNF-α gene expression. Furthermore, they suggest NFATp as a potential selective target in the treatment of superantigen-induced lethal shock. PMID:10952728

  13. Cloning animals by somatic cell nuclear transfer--biological factors.

    PubMed

    Tian, X Cindy; Kubota, Chikara; Enright, Brian; Yang, Xiangzhong

    2003-11-13

    Cloning by nuclear transfer using mammalian somatic cells has enormous potential application. However, somatic cloning has been inefficient in all species in which live clones have been produced. High abortion and fetal mortality rates are commonly observed. These developmental defects have been attributed to incomplete reprogramming of the somatic nuclei by the cloning process. Various strategies have been used to improve the efficiency of nuclear transfer, however, significant breakthroughs are yet to happen. In this review we will discuss studies conducted, in our laboratories and those of others, to gain a better understanding of nuclear reprogramming. Because cattle are a species widely used for nuclear transfer studies, and more laboratories have succeeded in cloning cattle than any other species, this review will be focused on somatic cell cloning of cattle.

  14. 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.

  15. Human factors design guidelines for maintainability of Department of Energy nuclear facilities

    SciTech Connect

    Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

    1985-06-18

    Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed.

  16. Featured Article: Hypoxia-inducible factor-1α dependent nuclear entry of factor inhibiting HIF-1

    PubMed Central

    Liang, Ke; Ding, Xue-qin; Lin, Chen

    2015-01-01

    The regulation of hypoxia-inducible factor-1 (HIF-1) transcriptional activity in the nucleus is related to factor inhibiting HIF-1 (FIH-1). FIH-1 hydrolyzes asparagine at the C-terminal of HIF-1α, preventing the interaction between HIF-1α and its associated cofactors, and leading to suppressed activation of HIF-1. FIH-1 is a cytosolic protein and its entry to the nucleus has to be coordinated with HIF-1α. The present study was undertaken to examine the correlation between HIF-1α and FIH-1 in their nuclear entry. Human umbilical vein endothelial cells were treated with dimethyloxalylglycine at a final concentration of 100 µM for 4 h, resulting in an accumulation of HIF-1α and an increase of FIH-1 in the nucleus as determined by Western blot analysis. Pretreatment of the cells with copper (Cu) chelator tetraethylenepentamine at 50 µM in cultures for 24 h reduced both HIF-1α protein levels and the HIF-1α entry to the nucleus, along with decreased FIH-1 protein levels in the nucleus but no changes in the total FIH-1 protein levels in the cells. These effects were prevented by simultaneous addition of 50 µM CuSO4 with tetraethylenepentamine. Gene-silencing of HIF-1α significantly inhibited FIH-1 entry to the nucleus, but did not affect the total protein levels of FIH-1 in the cells. This work demonstrates that the nuclear entry of FIH-1 depends on HIF-1α. Cu deficiency caused a decrease of HIF-1α, leading to suppression of FIH-1 entry to the nucleus. PMID:25687434

  17. Nuclear Factor-Y is an adipogenic factor that regulates leptin gene expression

    PubMed Central

    Lu, Yi-Hsueh; Dallner, Olof Stefan; Birsoy, Kivanc; Fayzikhodjaeva, Gulya; Friedman, Jeffrey M.

    2015-01-01

    Objective Leptin gene expression is highly correlated with cellular lipid content in adipocytes but the transcriptional mechanisms controlling leptin expression in vivo are poorly understood. In this report, we set out to identify cis- and trans-regulatory elements controlling leptin expression. Methods Leptin-BAC luciferase transgenic mice combining with other computational and molecular techniques were used to identify transcription regulatory elements including a CCAAT-binding protein Nuclear Factor Y (NF-Y). The function of NF-Y in adipocyte was studied in vitro with 3T3-L1 cells and in vivo with adipocyte-specific knockout of NF-Y. Results Using Leptin-BAC luciferase mice, we showed that DNA sequences between −22 kb and +8.8 kb can confer quantitative expression of a leptin reporter. Computational analysis of sequences and gel shift assays identified a 32 bp sequence (chr6: 28993820–2899385) consisting a CCAAT binding site for Nuclear Factor Y (NF-Y) and this was confirmed by a ChIP assay in vivo. A deletion of this 32 bp sequence in the −22 kb to +8.8 kb leptin-luciferase BAC reporter completely abrogates luciferase reporter activity in vivo. RNAi mediated knockdown of NF-Y interfered with adipogenesis in vitro and adipocyte-specific knockout of NF-Y in mice reduced expression of leptin and other fat specific genes in vivo. Further analyses of the fat specific NF-Y knockout revealed that these animals develop a moderately severe lipodystrophy that is remediable with leptin therapy. Conclusions These studies advance our understanding of leptin gene expression and show that NF-Y controls the expression of leptin and other adipocyte genes and identifies a new form of lipodystrophy. PMID:25973387

  18. Health Problems and Risk Factors Associated with Long Haul Transport of Horses in Australia

    PubMed Central

    Padalino, Barbara; Hall, Evelyn; Raidal, Sharanne; Celi, Pietro; Knight, Peter; Jeffcott, Leo; Muscatello, Gary

    2015-01-01

    Simple Summary Records from road transport of horses from Perth to Sydney over a two year period were analysed to explore the incidence of transport related issues and identify risk factors. Transportation resulted in health problems in 2.8% of the transported horses, and in fatalities in 0.24%. Journey duration and season were risk factors for the development of transport related health problems, while breed, sex and age did not predict disease or injury risk. Overall, this study provides statistics to inform policy development for the equine transport industry and enhance management of the transported horse. Abstract Equine transportation is associated with a variety of serious health disorders causing economic losses. However; statistics on horse transport are limited and epidemiological data on transport related diseases are available only for horses transported to abattoirs for slaughter. This study analysed reports of transport related health problems identified by drivers and horse owners for 180 journeys of an Australian horse transport company transporting horses between Perth and Sydney (~4000 km) in 2013–2015. Records showed that 97.2% (1604/1650) of the horses arrived at their destination with no clinical signs of disease or injury. Based on the veterinary reports of the affected horses; the most common issues were respiratory problems (27%); gastrointestinal problems (27%); pyrexia (19%); traumatic injuries (15%); and death (12%). Journey duration and season had a significant effect on the distribution of transport related issues (p < 0.05); with a marked increase of the proportion of the most severe problems (i.e., gastrointestinal; respiratory problems and death) in spring and after 20 h in transit. Although not statistically significant; elevated disease rate predictions were seen for stallions/colts; horses aged over 10 years; and Thoroughbreds. Overall; the data demonstrate that long haul transportation is a risk for horse health and welfare and

  19. Hypoxic preconditioning decreases nuclear factor κB activity via Disrupted in Schizophrenia-1.

    PubMed

    Liu, Jia-Ren; Liu, Qian; Khoury, Joseph; Li, Yue-Jin; Han, Xiao-Hui; Li, Jing; Ibla, Juan C

    2016-01-01

    Nuclear factor κB is a key mediator of inflammation during conditions of hypoxia. Here, we used models of hypoxic pre-conditioning as mechanism to decrease nuclear factor κB activity induced by hypoxia. Our initial studies suggested that Disrupted in Schizophrenia-1 may be induced by hypoxic pre-conditioning and possibly involved in the regulation of nuclear factor κB. In this study we used Disrupted in Schizophrenia-1 exogenous over-expression and knock-down to determine its effect on ataxia telangiectasia mutated--nuclear factor κB activation cascade. Our results demonstrated that hypoxic pre-conditioning significantly increased the expression of Disrupted in Schizophrenia-1 at mRNA and protein levels both in vitro and in vivo. Over-expression of Disrupted in Schizophrenia-1 significantly attenuated the hypoxia-mediated ataxia telangiectasia mutated phosphorylation and prevented its cytoplasm translocation where it functions to activate nuclear factor κB. We further determined that Disrupted in Schizophrenia-1 activated the protein phosphatase 2A, preventing the phosphorylation of ataxia telangiectasia mutated serine-1981, the main regulatory site of ataxia telangiectasia mutated activity. Cellular levels of Disrupted in Schizophrenia-1 protein significantly decreased nuclear factor κB activation profiles and pro-inflammatory gene expression. Taken together, these results demonstrate that hypoxic pre-conditioning decreases the activation of nuclear factor κB through the transcriptional induction of Disrupted in Schizophrenia-1.

  20. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes.

    PubMed

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. PMID:27012198

  1. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes.

    PubMed

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle.

  2. Release and transport of gaseous C-14 from a nuclear waste repository in an unsaturated medium

    SciTech Connect

    Light, W.B.; Zwahlen, E.D.; Pigford, T.H.; Chambre, P.L.; Lee, W.W.L.

    1990-11-01

    The potential nuclear waste repository at Yucca Mountain is to be in partially saturated rock. Released radioactive gases such as {sup 14}CO{sub 2} could have a direct pathway to the biosphere. We study the release of {sup 14}C released as {sup 14}CO{sub 2} from partly failed nuclear waste containers by analyzing the flow of gas into and out of a container. We analyze the transport of released {sup 14}CO{sub 2} in an unsaturated, fractured, porous medium with gas-phase advection and dispersion. We calculate the inhalation dose to a maximally exposed individual above ground, based on some conservative assumptions about release from containers. For the assumed parameter values, a simple atmospheric diffusion model gives very small doses when compared to background radiation doses. 12 refs., 4 figs., 1 tab.

  3. Nucleocytoplasmic transport of macromolecules.

    PubMed Central

    Corbett, A H; Silver, P A

    1997-01-01

    Nucleocytoplasmic transport is a complex process that consists of the movement of numerous macromolecules back and forth across the nuclear envelope. All macromolecules that move in and out of the nucleus do so via nuclear pore complexes that form large proteinaceous channels in the nuclear envelope. In addition to nuclear pores, nuclear transport of macromolecules requires a number of soluble factors that are found both in the cytoplasm and in the nucleus. A combination of biochemical, genetic, and cell biological approaches have been used to identify and characterize the various components of the nuclear transport machinery. Recent studies have shown that both import to and export from the nucleus are mediated by signals found within the transport substrates. Several studies have demonstrated that these signals are recognized by soluble factors that target these substrates to the nuclear pore. Once substrates have been directed to the pore, most transport events depend on a cycle of GTP hydrolysis mediated by the small Ras-like GTPase, Ran, as well as other proteins that regulate the guanine nucleotide-bound state of Ran. Many of the essential factors have been identified, and the challenge that remains is to determine the exact mechanism by which transport occurs. This review attempts to present an integrated view of our current understanding of nuclear transport while highlighting the contributions that have been made through studies with genetic organisms such as the budding yeast, Saccharomyces cerevisiae. PMID:9184010

  4. Chemical factors affecting fission product transport in severe LMFBR accidents

    SciTech Connect

    Wichner, R.P.; Jolley, R.L.; Gat, U.; Rodgers, B.R.

    1984-10-01

    This study was performed as a part of a larger evaluation effort on LMFBR accident, source-term estimation. Purpose was to provide basic chemical information regarding fission product, sodium coolant, and structural material interactions required to perform estimation of fission product transport under LMFBR accident conditions. Emphasis was placed on conditions within the reactor vessel; containment vessel conditions are discussed only briefly.

  5. Assessment of hydrologic transport of radionuclides from the Gnome underground nuclear test site, New Mexico

    SciTech Connect

    Earman, S.; Chapman, J.; Pohlmann, K.; Andricevic, R.

    1996-09-01

    The U.S. Department of Energy (DOE) is operating an environmental restoration program to characterize, remediate, and close non-Nevada Test Site locations that were used for nuclear testing. Evaluation of radionuclide transport by groundwater from these sites is an important part of the preliminary site risk analysis. These evaluations are undertaken to allow prioritization of the test areas in terms of risk, provide a quantitative basis for discussions with regulators and the public about future work at the sites, and provide a framework for assessing data needs to be filled by site characterization. The Gnome site in southeastern New Mexico was the location of an underground detonation of a 3.5-kiloton nuclear device in 1961, and a hydrologic tracer test using radionuclides in 1963. The tracer test involved the injection of tritium, {sup 90}Sr, and {sup 137}Cs directly into the Culebra Dolomite, a nine to ten-meter-thick aquifer located approximately 150 in below land surface. The Gnome nuclear test was carried out in the Salado Formation, a thick salt deposit located 200 in below the Culebra. Because salt behaves plastically, the cavity created by the explosion is expected to close, and although there is no evidence that migration has actually occurred, it is assumed that radionuclides from the cavity are released into the overlying Culebra Dolomite during this closure process. Transport calculations were performed using the solute flux method, with input based on the limited data available for the site. Model results suggest that radionuclides may be present in concentrations exceeding drinking water regulations outside the drilling exclusion boundary established by DOE. Calculated mean tritium concentrations peak at values exceeding the U.S. Environmental Protection Agency drinking water standard of 20,000 pCi/L at distances of up to almost eight kilometers west of the nuclear test.

  6. Girls' perception of physical environmental factors and transportation: reliability and association with physical activity and active transport to school

    PubMed Central

    Evenson, Kelly R; Birnbaum, Amanda S; Bedimo-Rung, Ariane L; Sallis, James F; Voorhees, Carolyn C; Ring, Kimberly; Elder, John P

    2006-01-01

    Background Preliminary evidence suggests that the physical environment and transportation are associated with youth physical activity levels. Only a few studies have examined the association of physical environmental factors on walking and bicycling to school. Therefore, the purpose of this study was (1) to examine the test-retest reliability of a survey designed for youth to assess perceptions of physical environmental factors (e.g. safety, aesthetics, facilities near the home) and transportation, and (2) to describe the associations of these perceptions with both physical activity and active transport to school. Methods Test and retest surveys, administered a median of 12 days later, were conducted with 480 sixth- and eighth-grade girls in or near six U.S. communities. The instrument consisted of 24 questions on safety and aesthetics of the perceived environment and transportation and related facilities. Additionally, girls were asked if they were aware of 14 different recreational facilities offering structured and unstructured activities, and if so, whether they would visit these facilities and the ease with which they could access them. Test-retest reliability was determined using kappa coefficients, overall and separately by grade. Associations with physical activity and active transport to school were examined using mixed model logistic regression (n = 610), adjusting for grade, race/ethnicity, and site. Results Item-specific reliabilities for questions assessing perceived safety and aesthetics of the neighborhood ranged from 0.31 to 0.52. Reliabilities of items assessing awareness of and interest in going to the 14 recreational facilities ranged from 0.47 to 0.64. Reliabilities of items assessing transportation ranged from 0.34 to 0.58. Some items on girls' perceptions of perceived safety, aesthetics of the environment, facilities, and transportation were important correlates of physical activity and, in some cases, active transport to school. Conclusion

  7. Reversible Bending Fatigue Test System for Investigating Vibration Integrity of Spent Nuclear Fuel during Transportation

    SciTech Connect

    Wang, Jy-An John; Wang, Hong; Bevard, Bruce Balkcom; Howard, Rob L; Flanagan, Michelle

    2013-01-01

    Transportation packages for spent nuclear fuel (SNF) must meet safety requirements under normal and accident conditions as specified by federal regulations. During transportation, SNF experiences unique conditions and challenges to cladding integrity due to the vibrational and impact loading during road or rail shipment. Oak Ridge National Laboratory (ORNL) has been developing testing capabilities that can be used to improve the understanding of the impacts on SNF integrity due to vibration loading, especially for high burn-up SNF in normal transportation operation conditions. This information can be used to meet the nuclear industry and U.S. Nuclear Regulatory Commission needs in the area of safety and security of spent nuclear fuel storage and transport operations. The ORNL developed test system can perform reversible-bending fatigue testing to evaluate both the static and dynamic mechanical response of SNF rods under simulated loads. The testing apparatus is also designed to meet the challenges of hot-cell operation, including remote installation and detachment of the SNF test specimen, in-situ test specimen deformation measurement, and implementation of a driving system suitable for use in a hot cell. The system contains a U-frame set-up equipped with uniquely designed grip rigs, to protect SNF rod and to ensure valid test results, and use of 3 specially designed LVDTs to obtain the in-situ curvature measurement. A variety of surrogate test rods have been used to develop and calibrate the test system as well as in performing a series of systematic cyclic fatigue tests. The surrogate rods include stainless steel (SS) cladding, SS cladding with cast epoxy, and SS cladding with alumina pellets inserts simulating fuel pellets. Testing to date has shown that the interface bonding between the SS cladding and the alumina pellets has a significant impact on the bending response of the test rods as well as their fatigue strength. The failure behaviors observed from

  8. Drosophila screen connects nuclear transport genes to DPR pathology in c9ALS/FTD

    PubMed Central

    Boeynaems, Steven; Bogaert, Elke; Michiels, Emiel; Gijselinck, Ilse; Sieben, Anne; Jovičić, Ana; De Baets, Greet; Scheveneels, Wendy; Steyaert, Jolien; Cuijt, Ivy; Verstrepen, Kevin J.; Callaerts, Patrick; Rousseau, Frederic; Schymkowitz, Joost; Cruts, Marc; Van Broeckhoven, Christine; Van Damme, Philip; Gitler, Aaron D.; Robberecht, Wim; Van Den Bosch, Ludo

    2016-01-01

    Hexanucleotide repeat expansions in C9orf72 are the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD) (c9ALS/FTD). Unconventional translation of these repeats produces dipeptide repeat proteins (DPRs) that may cause neurodegeneration. We performed a modifier screen in Drosophila and discovered a critical role for importins and exportins, Ran-GTP cycle regulators, nuclear pore components, and arginine methylases in mediating DPR toxicity. These findings provide evidence for an important role for nucleocytoplasmic transport in the pathogenic mechanism of c9ALS/FTD. PMID:26869068

  9. Thermally driven advection for radioxenon transport from an underground nuclear explosion

    NASA Astrophysics Data System (ADS)

    Sun, Yunwei; Carrigan, Charles R.

    2016-05-01

    Barometric pumping is a ubiquitous process resulting in migration of gases in the subsurface that has been studied as the primary mechanism for noble gas transport from an underground nuclear explosion (UNE). However, at early times following a UNE, advection driven by explosion residual heat is relevant to noble gas transport. A rigorous measure is needed for demonstrating how, when, and where advection is important. In this paper three physical processes of uncertain magnitude (oscillatory advection, matrix diffusion, and thermally driven advection) are parameterized by using boundary conditions, system properties, and source term strength. Sobol' sensitivity analysis is conducted to evaluate the importance of all physical processes influencing the xenon signals. This study indicates that thermally driven advection plays a more important role in producing xenon signals than oscillatory advection and matrix diffusion at early times following a UNE, and xenon isotopic ratios are observed to have both time and spatial dependence.

  10. Diffusion in an elastic medium: A model for macromolecule transport across the nuclear pore complex

    NASA Astrophysics Data System (ADS)

    Chakrabarti, Rajarshi; Debnath, Ananya; Sebastian, K. L.

    2014-06-01

    Nuclear pore complexes (NPCs) are very selective filters that sit on the membrane of the nucleus and monitor the transport between the cytoplasm and the nucleoplasm. For the central plug of NPC two models have been suggested in the literature. The first suggests that the plug is a reversible hydrogel while the other suggests that it is a polymer brush. Here we propose a model for the transport of a protein through the plug, which is general enough to cover both the models. The protein stretches the plug and creates a local deformation, which together with the protein, we refer to as the bubble. We start with the free energy for creation of the bubble and consider its motion within the plug. The relevant coordinate is the center of the bubble which executes random walk. We find that for faster relaxation of the gel, the diffusion of the bubble is greater.

  11. Efficient Nuclear Transport of Structurally Disturbed Cargo: Mutations in a Cargo Protein Switch Its Cognate Karyopherin

    PubMed Central

    Chaves, Susana R.; Rosenblum, Jonathan S.

    2011-01-01

    The Karyopherin (Kap) family of nuclear transport receptors enables trafficking of proteins to and from the nucleus in a precise, regulated manner. Individual members function in overlapping pathways, while simultaneously being very specific for their main cargoes. The details of this apparent contradiction and rules governing pathway preference remain to be further elucidated. S. cerevisiae Lhp1 is an abundant protein that functions as an RNA chaperone in a variety of biologically important processes. It localizes almost exclusively to the nucleus and is imported by Kap108. We show that mutation of 3 of the 275 residues in Lhp1 alters its import pathway to a Kap121-dependent process. This mutant does not retain wild-type function and is bound by several chaperones. We propose that Kap121 also acts as a chaperone, one that can act as a genetic buffer by transporting mutated proteins to the nucleus. PMID:21347375

  12. Transportation Energy Futures Series: Effects of the Built Environment on Transportation: Energy Use, Greenhouse Gas Emissions, and Other Factors

    SciTech Connect

    Porter, C. D.; Brown, A.; Dunphy, R. T.; Vimmerstedt, L.

    2013-03-01

    Planning initiatives in many regions and communities aim to reduce transportation energy use, decrease emissions, and achieve related environmental benefits by changing land use. This report reviews and summarizes findings from existing literature on the relationship between the built environment and transportation energy use and greenhouse gas emissions, identifying results trends as well as potential future actions. The indirect influence of federal transportation and housing policies, as well as the direct impact of municipal regulation on land use are examined for their effect on transportation patterns and energy use. Special attention is given to the 'four D' factors of density, diversity, design and accessibility. The report concludes that policy-driven changes to the built environment could reduce transportation energy and GHG emissions from less than 1% to as much as 10% by 2050, the equivalent of 16%-18% of present-day urban light-duty-vehicle travel. This is one of a series of reports produced as a result of the Transportation Energy Futures (TEF) project, a Department of Energy-sponsored multi-agency project initiated to pinpoint underexplored strategies for abating GHGs and reducing petroleum dependence related to transportation.

  13. Transportation Energy Futures Series. Effects of the Built Environment on Transportation. Energy Use, Greenhouse Gas Emissions, and Other Factors

    SciTech Connect

    Porter, C. D.; Brown, A.; Dunphy, R. T.; Vimmerstedt, L.

    2013-03-15

    Planning initiatives in many regions and communities aim to reduce transportation energy use, decrease emissions, and achieve related environmental benefits by changing land use. This report reviews and summarizes findings from existing literature on the relationship between the built environment and transportation energy use and greenhouse gas emissions, identifying results trends as well as potential future actions. The indirect influence of federal transportation and housing policies, as well as the direct impact of municipal regulation on land use are examined for their effect on transportation patterns and energy use. Special attention is given to the 'four D' factors of density, diversity, design and accessibility. The report concludes that policy-driven changes to the built environment could reduce transportation energy and GHG emissions from less than 1% to as much as 10% by 2050, the equivalent of 16%-18% of present-day urban light-duty-vehicle travel. This is one of a series of reports produced as a result of the Transportation Energy Futures (TEF) project, a Department of Energy-sponsored multi-agency project initiated to pinpoint underexplored strategies for abating GHGs and reducing petroleum dependence related to transportation.

  14. Mass transfer and transport of radionuclides through backfill in a geologic nuclear waster repository

    SciTech Connect

    Kang, Chulhyung.

    1989-01-01

    Analytical models for the mass transfer and transport of radionuclides through waste package backfill material are developed and their numerical illustrations are demonstrated. These models can aid in the performance assessment of the waste package in nuclear waste repositories. The following analyses are considered to study the performance of the backfill barrier in a geologic nuclear waste repository. (1) The analysis for time and space dependent mass transfer and mass transport of a radioactive decay chain for a congruent release with the matrix species is studied. Non-recursive analytical solutions are derived for a semi-infinite medium and a finite medium. The theory is illustrated with the important decay chain {sup 234}U {yields} {sup 230}Th {yields} {sup 226}Ra. (2) The time and space dependent mass transport for high solubility nuclides, such as iodine or cesium, is analyzed. The approximate solution that is valid for all times is developed, and validated by comparison with an asymptotic solution and the solution obtained by the numerical inversion of a Laplace transform covering the entire time span. From this model one can determine the thickness of the backfill to satisfy a prescribed release rate limit for high soluble radionuclides. (3) The analysis of the transient radionuclide migration through the backfill into a fracture intersecting the waste form is developed. The nuclides are advected by water flowing in the fracture. The numerical illustrations show that the species transport for the short half-life nuclide can be stopped effectively within the backfill, but the backfill can no longer retard the migration for stable nuclides or long half-life nuclides after some initial time period. (4) The steady state mass transfer from a cylindrical waste form with flow through the backfill layer is examined.

  15. Integrated System for Retrieval, Transportation and Consolidated Storage of Used Nuclear Fuel in the US - 13312

    SciTech Connect

    Bracey, William; Bondre, Jayant; Shelton, Catherine; Edmonds, Robert

    2013-07-01

    The current inventory of used nuclear fuel assemblies (UNFAs) from commercial reactor operations in the United States totals approximately 65,000 metric tons or approximately 232,000 UNFAs primarily stored at the 104 operational reactors in the US and a small number of decommissioned reactors. This inventory is growing at a rate of roughly 2,000 to 2,400 metric tons each year, (Approx. 7,000 UNFAs) as a result of ongoing commercial reactor operations. Assuming an average of 10 metric tons per storage/transportation casks, this inventory of commercial UNFAs represents about 6,500 casks with an additional of about 220 casks every year. In January 2010, the Blue Ribbon Commission (BRC) [1] was directed to conduct a comprehensive review of policies for managing the back end of the nuclear fuel cycle and recommend a new plan. The BRC issued their final recommendations in January 2012. One of the main recommendations is for the United States to proceed promptly to develop one or more consolidated storage facilities (CSF) as part of an integrated, comprehensive plan for safely managing the back end of the nuclear fuel cycle. Based on its extensive experience in storage and transportation cask design, analysis, licensing, fabrication, and operations including transportation logistics, Transnuclear, Inc. (TN), an AREVA Subsidiary within the Logistics Business Unit, is engineering an integrated system that will address the complete process of commercial UNFA management. The system will deal with UNFAs in their current storage mode in various configurations, the preparation including handling and additional packaging where required and transportation of UNFAs to a CSF site, and subsequent storage, operation and maintenance at the CSF with eventual transportation to a future repository or recycling site. It is essential to proceed by steps to ensure that the system will be the most efficient and serve at best its purpose by defining: the problem to be resolved, the criteria to

  16. Measurement and modelling of reactive transport in geological barriers for nuclear waste containment.

    PubMed

    Xiong, Qingrong; Joseph, Claudia; Schmeide, Katja; Jivkov, Andrey P

    2015-11-11

    Compacted clays are considered as excellent candidates for barriers to radionuclide transport in future repositories for nuclear waste due to their very low hydraulic permeability. Diffusion is the dominant transport mechanism, controlled by a nano-scale pore system. Assessment of the clays' long-term containment function requires adequate modelling of such pore systems and their evolution. Existing characterisation techniques do not provide complete pore space information for effective modelling, such as pore and throat size distributions and connectivity. Special network models for reactive transport are proposed here using the complimentary character of the pore space and the solid phase. This balances the insufficient characterisation information and provides the means for future mechanical-physical-chemical coupling. The anisotropy and heterogeneity of clays is represented using different length parameters and percentage of pores in different directions. Resulting networks are described as mathematical graphs with efficient discrete calculus formulation of transport. Opalinus Clay (OPA) is chosen as an example. Experimental data for the tritiated water (HTO) and U(vi) diffusion through OPA are presented. Calculated diffusion coefficients of HTO and uranium species are within the ranges of the experimentally determined data in different clay directions. This verifies the proposed pore network model and validates that uranium complexes are diffusing as neutral species in OPA. In the case of U(vi) diffusion the method is extended to account for sorption and convection. Rather than changing pore radii by coarse grained mathematical formula, physical sorption is simulated in each pore, which is more accurate and realistic.

  17. Molecular Architecture of the Transport Channel of the Nuclear Pore Complex

    PubMed Central

    Solmaz, Sozanne R.; Chauhan, Radha; Blobel, Günter; Melčák, Ivo

    2012-01-01

    SUMMARY The nuclear pore complex encloses a central channel for nucleocytoplasmic transport, which is thought to consist of three nucleoporins, Nup54, Nup58, and Nup62. However, the structure and composition of the channel are elusive. We determined the crystal structures of the interacting domains between these nucleoporins and pieced together the molecular architecture of the mammalian transport channel. Located in the channel midplane is a flexible Nup54·Nup58 ring that can undergo large rearrangements yielding diameter changes from ~20 to ~40 nm. Nup62·Nup54 triple helices project alternately up and down from either side of the midplane ring and form nucleoplasmic and cytoplasmic entries. The channel consists of as many as 224 copies of the three nucleoporins, amounting to a molar mass of 12.3 MDa and contributing 256 phenylalanine-glycine repeat regions. We propose that the occupancy of these repeat regions with transport receptors modulates ring diameter and transport activity. PMID:22036567

  18. Transportation infrastructure upgrades in the South: A compilation of state plans for construction near nuclear reactor sites

    SciTech Connect

    Not Available

    1992-03-01

    There are currently 27 nuclear reactor sites located in the southern region. In many instances, the most practicable modes of transportation of spent nuclear fuel from these sites we through the use of highway and rail systems. These two transportation modes have important differences that affect their applicability; chief among these, perhaps, is the fact that while highway systems are publicly owned and maintained rail lines are owned by private entities. For this reason, track condition and maintenance, usage rates and other aspects of rail transport can vary widely. This report reviews southern state, department plans for infrastructure upgrades in the vicinity of nuclear reactor sites. This report includes a summary of planned modifications to bridges, access highways, and rail spurs (where applicable) over the next five years. The information contained herein was gathered from interviews with officials within state departments of transportation. With few exceptions, the contact person was an official within the departmental planning division.

  19. Nuclear factor erythroid 2-related factor gene variants and susceptibility of arsenic-related skin lesions.

    PubMed

    Cordova, E J; Valenzuela, O L; Sánchez-Peña, L C; Escamilla-Guerrero, G; Hernández-Zavala, A; Orozco, L; Del Razo, L M

    2014-06-01

    Inorganic arsenic (iAs) is an important pollutant associated with various chronic-degenerative diseases. The cytoprotective protein nuclear factor erythroid 2-related factor (NRF2) has been proposed as an important responsive mechanism against iAs exposure. The aim of this study was to determine whether the risk of skin lesions in people exposed to iAs-contaminated water could be modified by the presence of single nucleotide polymorphisms in the NRF2 coding gene. We studied 117 individuals with long-term iAs exposure and 120 nonexposed individuals. Total As was determined in water, meanwhile iAs and its metabolites were measured in urine. The iAs-induced skin lesion status was evaluated by expert dermatologists. We sequenced the promoter region of NRF2 in a sample of 120 healthy donors. We found four polymorphisms previously reported and one novel polymorphism in the 5' regulatory region of the NRF2. In this study, we did not find allelic and genotype association of NRF2 polymorphisms with iAs-related skin lesion. However, the analysis of haplotypes composed by -653GA, and -617CA NRF2 single nucleotide polymorphisms showed a significant association with protection against skin lesions in the low-As exposure group. This is the first report studying the association between NRF2 polymorphisms and susceptibility of As-related skin lesions. Increasing the sample size will allow us to confirm this data. PMID:24107458

  20. Nuclear factor erythroid 2-related factor gene variants and susceptibility of arsenic-related skin lesions.

    PubMed

    Cordova, E J; Valenzuela, O L; Sánchez-Peña, L C; Escamilla-Guerrero, G; Hernández-Zavala, A; Orozco, L; Del Razo, L M

    2014-06-01

    Inorganic arsenic (iAs) is an important pollutant associated with various chronic-degenerative diseases. The cytoprotective protein nuclear factor erythroid 2-related factor (NRF2) has been proposed as an important responsive mechanism against iAs exposure. The aim of this study was to determine whether the risk of skin lesions in people exposed to iAs-contaminated water could be modified by the presence of single nucleotide polymorphisms in the NRF2 coding gene. We studied 117 individuals with long-term iAs exposure and 120 nonexposed individuals. Total As was determined in water, meanwhile iAs and its metabolites were measured in urine. The iAs-induced skin lesion status was evaluated by expert dermatologists. We sequenced the promoter region of NRF2 in a sample of 120 healthy donors. We found four polymorphisms previously reported and one novel polymorphism in the 5' regulatory region of the NRF2. In this study, we did not find allelic and genotype association of NRF2 polymorphisms with iAs-related skin lesion. However, the analysis of haplotypes composed by -653GA, and -617CA NRF2 single nucleotide polymorphisms showed a significant association with protection against skin lesions in the low-As exposure group. This is the first report studying the association between NRF2 polymorphisms and susceptibility of As-related skin lesions. Increasing the sample size will allow us to confirm this data.

  1. Correlation Between Nuclear Factor E2-Related Factor 2 Expression and Gastric Cancer Progression

    PubMed Central

    Zheng, Hongyu; Nong, Zhiwei; Lu, Guohao

    2015-01-01

    Background Nuclear factor E2-related factor 2 (Nrf2) plays an anti-oxidative and phase II detoxification function via its up-regulation on various antioxidant response elements (ARE) genes. Nrf2 can protect both normal and cancer cells from damages of cell stress, thereby exerting a critical role in the development of cancer. The expression and significance of Nrf2 in gastric cancer, however, has not been reported. This study thus aimed to investigate the expression of Nrf2 in gastric cancer tissues via immunohistochemical (IHC) staining. Material/Methods Gastric carcinoma tissues from a total of 175 patients during surgical resection were examined for Nfr2 expression profiles using IHC staining on paraffin-embedded slides. Between-group-comparisons were performed by chi-square, Fisher’s exact, or Mann-Whitney U test. The correlation between Nfr2 expression and clinical indexes was further analyzed by Kaplan-Meier test, univariate/multivariate analysis, and log-rank test. Results Nrf2 is mainly expressed in nuclei of gastric carcinoma tissues, with significant correlation with clinical indexes, including tumor size, invasive depth, lymph node metastasis, and invasion. Patients with Nrf2-positive expression had significantly lower survival rates compared to those in the negative group (p<0.01), with chemo-resistance against 5-fluorouracil (5-FU) (p<0.05). Conclusions Nrf2 expression is positively correlated with invasive gastric cancer, suggesting its utility as a predictive index for unfavorable prognosis. PMID:26410168

  2. AP-42 ADDITIONS AND REVISIONS - TRANSPORTABILITY FACTORS FOR FUGITIVE DUST

    EPA Science Inventory

    The product is a table of factors, one for each county in the US, reflecting the portion of fugitive dust removed very close to the source via impaction on vegetation and similar mechanisms. Factors were based on land cover in area (county or grid cell) A praft final product was...

  3. Modulation of epidermal growth factor effects on epithelial ion transport by intestinal trefoil factor.

    PubMed

    Chinery, R; Cox, H M

    1995-05-01

    1. The direct epithelial effects of epidermal growth factor (EGF) and its modulation by intestinal trefoil factor (ITF) have been studied in a human colonic adenocarcinoma cell line called Colony-29 (Col-29). 2. When grown in culture as confluent monolayers and voltage-clamped in Ussing chambers, these epithelia responded with an increase in short circuit current (SCC) to basolateral as well as to apically applied EGF although the latter responses (at 10 nM) were only 25% of those observed following basolateral peptide. 3. Recombinant rat ITF (added to the basolateral surface) did not alter basal SCC levels, but it did enhance the electrogenic effects of basolateral EGF. The EC50 values for EGF-induced ion transport were 0.25 nM in control, and 0.26 nM in ITF pretreated Col-29 epithelia. A significant increase in the size of EGF responses (0.1 nM-10 nM) was observed in the presence of 10 nM ITF and the half-maximal concentration for this modulatory effect of ITF was 7.6 nM. 4. The EGF-induced increases in SCC were partially inhibited (50%) by piretanide pretreatment, indicating that Cl- secretion is involved. EGF responses either in the presence or absence of ITF were also significantly reduced (84% and 66% respectively) by the cyclo-oxygenase inhibitor, piroxicam, therefore implicating prostaglandins as mediators of EGF-stimulated anion secretion. 5. We conclude that in confluent Col-29 epithelia, basolateral EGF stimulates a predominantly prostaglandin-dependent increase in Cl- secretion that is enhanced by basolateral ITF, and that these two peptides may interact in normal and damaged mucosa to alter the local apical solute and fluid environment.

  4. Functional insights of nucleocytoplasmic transport in plants

    PubMed Central

    Tamura, Kentaro; Hara-Nishimura, Ikuko

    2014-01-01

    Plant nucleocytoplasmic transport beyond the nuclear envelope is important not only for basic cellular functions but also for growth, development, hormonal signaling, and responses to environmental stimuli. Key components of this transport system include nuclear transport receptors and nucleoporins. The functional and physical interactions between receptors and the nuclear pore in the nuclear membrane are indispensable for nucleocytoplasmic transport. Recently, several groups have reported various plant mutants that are deficient in factors involved in nucleocytoplasmic transport. Here, we summarize the current state of knowledge about nucleocytoplasmic transport in plants, and we review the plant-specific regulation and roles of this process in plants. PMID:24765097

  5. The rationale/benefits of nuclear thermal rocket propulsion for NASA's lunar space transportation system

    NASA Astrophysics Data System (ADS)

    Borowski, Stanley K.

    1994-09-01

    The solid core nuclear thermal rocket (NTR) represents the next major evolutionary step in propulsion technology. With its attractive operating characteristics, which include high specific impulse (approximately 850-1000 s) and engine thrust-to-weight (approximately 4-20), the NTR can form the basis for an efficient lunar space transportation system (LTS) capable of supporting both piloted and cargo missions. Studies conducted at the NASA Lewis Research Center indicate that an NTR-based LTS could transport a fully-fueled, cargo-laden, lunar excursion vehicle to the Moon, and return it to low Earth orbit (LEO) after mission completion, for less initial mass in LEO than an aerobraked chemical system of the type studied by NASA during its '90-Day Study.' The all-propulsive NTR-powered LTS would also be 'fully reusable' and would have a 'return payload' mass fraction of approximately 23 percent--twice that of the 'partially reusable' aerobraked chemical system. Two NTR technology options are examined--one derived from the graphite-moderated reactor concept developed by NASA and the AEC under the Rover/NERVA (Nuclear Engine for Rocket Vehicle Application) programs, and a second concept, the Particle Bed Reactor (PBR). The paper also summarizes NASA's lunar outpost scenario, compares relative performance provided by different LTS concepts, and discusses important operational issues (e.g., reusability, engine 'end-of life' disposal, etc.) associated with using this important propulsion technology.

  6. Study of the contaminant transport into granite microfractures using nuclear ion beam techniques.

    PubMed

    Alonso, Ursula; Missana, Tiziana; Patelli, Alessandro; Rigato, Valentino; Rivas, Pedro

    2003-03-01

    Hydrated bentonite is a very plastic material and it is expected to enter in the rock microfractures at the granite/bentonite boundary of a deep geological high-level waste repository. This process is enhanced by the high swelling pressure of the clay. Since bentonite has a very good sorption capability for many radionuclides, the displacement of the clay might lead to a "clay-mediated" contaminant transport into the rock. The aim of this work is to study the contaminant transport into granite microfractures using nuclear ion beam techniques, and to determine to what extent the clay can favour it. To do so, bentonite previously doped with uranium, cesium and europium was put in contact with the surface of granite sheets. Granite sheets contacted with non-doped bentonite and with radionuclide solutions were also prepared as references. This allowed analysing the differences in the diffusion behaviour of the three systems: clay, radionuclides and clay plus radionuclides. A combination of Rutherford backscattering spectrometry (RBS) and other nuclear ion-beam techniques such as particle-induced X-ray emission (PIXE) and microPIXE was used to study the depth and lateral distribution of clay and contaminants inside granite. It was also tried to evaluate not only the diffusion depth and diffusion coefficients but also the different areas of the granite where the diffusants have a preferential access.

  7. A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies

    PubMed Central

    Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

    2016-01-01

    The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior – a key element for the transport selectivity of the NPC – was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface. DOI: http://dx.doi.org/10.7554/eLife.14119.001 PMID:27058170

  8. DUSCOBS - a depleted-uranium silicate backfill for transport, storage, and disposal of spent nuclear fuel

    SciTech Connect

    Forsberg, C.W.; Pope, R.B.; Ashline, R.C.; DeHart, M.D.; Childs, K.W.; Tang, J.S.

    1995-11-30

    A Depleted Uranium Silicate COntainer Backfill System (DUSCOBS) is proposed that would use small, isotopically-depleted uranium silicate glass beads as a backfill material inside storage, transport, and repository waste packages containing spent nuclear fuel (SNF). The uranium silicate glass beads would fill all void space inside the package including the coolant channels inside SNF assemblies. Based on preliminary analysis, the following benefits have been identified. DUSCOBS improves repository waste package performance by three mechanisms. First, it reduces the radionuclide releases from SNF when water enters the waste package by creating a local uranium silicate saturated groundwater environment that suppresses (1) the dissolution and/or transformation of uranium dioxide fuel pellets and, hence, (2) the release of radionuclides incorporated into the SNF pellets. Second, the potential for long-term nuclear criticality is reduced by isotopic exchange of enriched uranium in SNF with the depleted uranium (DU) in the glass. Third, the backfill reduces radiation interactions between SNF and the local environment (package and local geology) and thus reduces generation of hydrogen, acids, and other chemicals that degrade the waste package system. In addition, the DUSCOBS improves the integrity of the package by acting as a packing material and ensures criticality control for the package during SNF storage and transport. Finally, DUSCOBS provides a potential method to dispose of significant quantities of excess DU from uranium enrichment plants at potential economic savings. DUSCOBS is a new concept. Consequently, the concept has not been optimized or demonstrated in laboratory experiments.

  9. The Rationale/Benefits of Nuclear Thermal Rocket Propulsion for NASA's Lunar Space Transportation System

    NASA Technical Reports Server (NTRS)

    Borowski, Stanley K.

    1994-01-01

    The solid core nuclear thermal rocket (NTR) represents the next major evolutionary step in propulsion technology. With its attractive operating characteristics, which include high specific impulse (approximately 850-1000 s) and engine thrust-to-weight (approximately 4-20), the NTR can form the basis for an efficient lunar space transportation system (LTS) capable of supporting both piloted and cargo missions. Studies conducted at the NASA Lewis Research Center indicate that an NTR-based LTS could transport a fully-fueled, cargo-laden, lunar excursion vehicle to the Moon, and return it to low Earth orbit (LEO) after mission completion, for less initial mass in LEO than an aerobraked chemical system of the type studied by NASA during its '90-Day Study.' The all-propulsive NTR-powered LTS would also be 'fully reusable' and would have a 'return payload' mass fraction of approximately 23 percent--twice that of the 'partially reusable' aerobraked chemical system. Two NTR technology options are examined--one derived from the graphite-moderated reactor concept developed by NASA and the AEC under the Rover/NERVA (Nuclear Engine for Rocket Vehicle Application) programs, and a second concept, the Particle Bed Reactor (PBR). The paper also summarizes NASA's lunar outpost scenario, compares relative performance provided by different LTS concepts, and discusses important operational issues (e.g., reusability, engine 'end-of life' disposal, etc.) associated with using this important propulsion technology.

  10. Mapping neural circuits with activity-dependent nuclear import of a transcription factor.

    PubMed

    Masuyama, Kaoru; Zhang, Yi; Rao, Yi; Wang, Jing W

    2012-03-01

    Abstract: Nuclear factor of activated T cells (NFAT) is a calcium-responsive transcription factor. We describe here an NFAT-based neural tracing method-CaLexA (calcium-dependent nuclear import of LexA)-for labeling active neurons in behaving animals. In this system, sustained neural activity induces nuclear import of the chimeric transcription factor LexA-VP16-NFAT, which in turn drives green fluorescent protein (GFP) reporter expression only in active neurons. We tested this system in Drosophila and found that volatile sex pheromones excite specific neurons in the olfactory circuit. Furthermore, complex courtship behavior associated with multi-modal sensory inputs activated neurons in the ventral nerve cord. This method harnessing the mechanism of activity-dependent nuclear import of a transcription factor can be used to identify active neurons in specific neuronal population in behaving animals. PMID:22236090

  11. Factors controlling mercury transport in an upland forested catchment

    USGS Publications Warehouse

    Scherbatskoy, T.; Shanley, J.B.; Keeler, G.J.

    1998-01-01

    Total mercury (Hg) deposition and input/output relationships were investigated in an 11-ha deciduous forested catchment in northern Vermont as part of ongoing evaluations of rig cycling and transport in the Lake Champlain basin. Atmospheric Hg deposition (precipitation + modeled vapor phase downward flux) was 425 mg ha-1 during the one-year period March 1994 through February 1995 and 463 mg ha-1 from March 1995 through February 1996. In the same periods, stream export of total Hg was 32 mg ha-1 and 22 mg ha-1, respectively. Thus, there was a net retention of Hg by the catchment of 92% the first year and 95% the second year. In the first year, 16.9 mg ha-1 or about half of the annual stream export, occurred on the single day of peak spring snowmelt in April. In contrast, the maximum daily export in the second year, when peak stream flow was somewhat lower, was 3.5 mg ha-1 during a January thaw. The fate of file Hg retained by this forested catchment is not known. Dissolved (< 0.22 ??m) Hg concentrations in stream water ranged from 0.5-2.6 ng L-1, even when total (unfiltered) concentrations were greater than 10 ng L-1 during high flow events. Total Hg concentrations in stream water were correlated with the total organic fraction of suspended sediment, suggesting the importance of organic material in Hg transport within the catchment. High flow events and transport with organic material may be especially important mechanisms for the movement of Hg through forested ecosystems.

  12. Competition between Different S-Components for the Shared Energy Coupling Factor Module in Energy Coupling Factor Transporters.

    PubMed

    Majsnerowska, Maria; Ter Beek, Josy; Stanek, Weronika K; Duurkens, Ria H; Slotboom, Dirk J

    2015-08-11

    Energy coupling factor (ECF) transporters take up micronutrients in Bacteria and Archaea. They consist of a membrane-embedded S-component that provides substrate specificity and a three-subunit ECF module that couples ATP hydrolysis to transport. The S-components ThiT (for thiamin) and NiaX (for niacin) from Lactococcus lactis form complexes with the same ECF module. Here, we assayed the uptake of thiamin and niacin in Escherichia coli cells expressing the transporter genes. We demonstrate that the two different S-components compete for the ECF module, and that competition is more efficient in the presence of the transported substrate. The data suggest that binding and release of the S-components is a step in the transport cycle.

  13. [The targeted transport of the medicinal substances and the therapeutic physical factors].

    PubMed

    Ulashchik, V S

    2014-01-01

    The present review describes the existing systems for the directed transport of the medicines to the target organs. The article presents the data on the use of the protein vectors, nanoparticles, artificial and natural containers for the targeted delivery of the pharmaceutical products. The potential applications of the physical factors for the directed transport of medicinal substances are considered.

  14. Atomistic Simulations of Mass and Thermal Transport in Oxide Nuclear Fuels

    SciTech Connect

    Andersson, Anders D.; Uberuaga, Blas P.; Du, Shiyu; Liu, Xiang-Yang; Nerikar, Pankaj; Stanek, Christopher R.; Tonks, Michael; Millet, Paul; Biner, Bulent

    2012-06-04

    In this talk we discuss simulations of the mass and thermal transport in oxide nuclear fuels. Redistribution of fission gases such as Xe is closely coupled to nuclear fuel performance. Most fission gases have low solubility in the fuel matrix, specifically the insolubility is most pronounced for large fission gas atoms such as Xe, and as a result there is a significant driving force for segregation of gas atoms to grain boundaries or dislocations and subsequently for nucleation of gas bubbles at these sinks. The first step of the fission gas redistribution is diffusion of individual gas atoms through the fuel matrix to existing sinks, which is governed by the activation energy for bulk diffusion. Fission gas bubbles are then formed by either separate nucleation events or by filling voids that were nucleated at a prior stage; in both cases their formation and latter growth is coupled to vacancy dynamics and thus linked to the production of vacancies via irradiation or thermal events. In order to better understand bulk Xe behavior (diffusion mechanisms) in UO{sub 2{+-}x} we first calculate the relevant activation energies using density functional theory (DFT) techniques. By analyzing a combination of Xe solution thermodynamics, migration barriers and the interaction of dissolved Xe atoms with U, we demonstrate that Xe diffusion predominantly occurs via a vacancy-mediated mechanism, though other alternatives may exist in high irradiation fields. Since Xe transport is closely related to diffusion of U vacancies, we have also studied the activation energy for this process. In order to explain the low value of 2.4 eV found for U migration from independent damage experiments (not thermal equilibrium) the presence of vacancy clusters must be included in the analysis. Next a continuum transport model for Xe and U is formulated based on the diffusion mechanisms established from DFT. After combining this model with descriptions of the interaction between Xe and grain

  15. Reversal bending fatigue test system for investigating vibration integrity of spent nuclear fuel during transportation

    SciTech Connect

    Wang, Jy -An; Wang, Hong; Bevard, Bruce Balkcom; Howard, Rob L.; Flanagan, Michelle E.

    2014-09-01

    Transportation packages for spent nuclear fuel (SNF) must meet safety requirements under normal and accident conditions as specified by federal regulations. During transportation, SNF experiences unique conditions and challenges to cladding integrity due to the vibrational and impact loading during road or rail shipment. Oak Ridge National Laboratory (ORNL) has been developing testing capabilities that can be used to improve the understanding of the impacts on SNF integrity due to vibration loading, especially for high burn-up SNF in normal transportation operation conditions. This information can be used to meet the nuclear industry and U.S.Nuclear Regulatory Commission needs in the area of safety and security of SNF storage and transportation operations. The ORNL developed test system can perform reversal bending fatigue testing to evaluate both the static and dynamic mechanical response of SNF rods under simulated loads. The testing apparatus is also designed to meet the challenges of hot cell operation, including remote installation and detachment of the SNF test specimen, in situ test specimen deformation measurement, and implementation of a driving system suitable for use in a hot cell. The system contains a U frame set-up equipped with uniquely designed grip rigs to protect the SNF rod sample and to ensure valid test results, and uses three specially designed linear variable differential transformers to obtain the in situ curvature measurement. A variety of surrogate test rods have been used to develop and calibrate the test system as well as in performing a series of systematic cyclic fatigue tests. The surrogate rods include stainless steel (SS) cladding, SS cladding with cast epoxy and SS cladding with alumina pellet inserts simulating fuel pellets. Testing to date has shown that the interface bonding between the SS cladding and the alumina pellets has a significant impact on the bending response of the test rods as well as their fatigue strength. The

  16. Reversal bending fatigue test system for investigating vibration integrity of spent nuclear fuel during transportation

    DOE PAGES

    Wang, Jy -An; Wang, Hong; Bevard, Bruce Balkcom; Howard, Rob L.; Flanagan, Michelle E.

    2014-09-01

    Transportation packages for spent nuclear fuel (SNF) must meet safety requirements under normal and accident conditions as specified by federal regulations. During transportation, SNF experiences unique conditions and challenges to cladding integrity due to the vibrational and impact loading during road or rail shipment. Oak Ridge National Laboratory (ORNL) has been developing testing capabilities that can be used to improve the understanding of the impacts on SNF integrity due to vibration loading, especially for high burn-up SNF in normal transportation operation conditions. This information can be used to meet the nuclear industry and U.S.Nuclear Regulatory Commission needs in the areamore » of safety and security of SNF storage and transportation operations. The ORNL developed test system can perform reversal bending fatigue testing to evaluate both the static and dynamic mechanical response of SNF rods under simulated loads. The testing apparatus is also designed to meet the challenges of hot cell operation, including remote installation and detachment of the SNF test specimen, in situ test specimen deformation measurement, and implementation of a driving system suitable for use in a hot cell. The system contains a U frame set-up equipped with uniquely designed grip rigs to protect the SNF rod sample and to ensure valid test results, and uses three specially designed linear variable differential transformers to obtain the in situ curvature measurement. A variety of surrogate test rods have been used to develop and calibrate the test system as well as in performing a series of systematic cyclic fatigue tests. The surrogate rods include stainless steel (SS) cladding, SS cladding with cast epoxy and SS cladding with alumina pellet inserts simulating fuel pellets. Testing to date has shown that the interface bonding between the SS cladding and the alumina pellets has a significant impact on the bending response of the test rods as well as their fatigue strength

  17. Changes in the Factors Influencing Public Acceptance of Nuclear Power Generation in Japan Since the 2011 Fukushima Daiichi Nuclear Disaster.

    PubMed

    Tsujikawa, Norifumi; Tsuchida, Shoji; Shiotani, Takamasa

    2016-01-01

    Public support for nuclear power generation has decreased in Japan since the Fukushima Daiichi nuclear accident in March 2011. This study examines how the factors influencing public acceptance of nuclear power changed after this event. The influence factors examined are perceived benefit, perceived risk, trust in the managing bodies, and pro-environmental orientation (i.e., new ecological paradigm). This study is based on cross-sectional data collected from two online nationwide surveys: one conducted in November 2009, before the nuclear accident, and the other in October 2011, after the accident. This study's target respondents were residents of Aomori, Miyagi, and Fukushima prefectures in the Tohoku region of Japan, as these areas were the epicenters of the Great East Japan Earthquake and the locations of nuclear power stations. After the accident, trust in the managing bodies was found to have a stronger influence on perceived risk, and pro-environmental orientation was found to have a stronger influence on trust in the managing bodies; however, perceived benefit had a weaker positive influence on public acceptance. We also discuss the theoretical and practical implications of these findings. PMID:26224041

  18. Changes in the Factors Influencing Public Acceptance of Nuclear Power Generation in Japan Since the 2011 Fukushima Daiichi Nuclear Disaster.

    PubMed

    Tsujikawa, Norifumi; Tsuchida, Shoji; Shiotani, Takamasa

    2016-01-01

    Public support for nuclear power generation has decreased in Japan since the Fukushima Daiichi nuclear accident in March 2011. This study examines how the factors influencing public acceptance of nuclear power changed after this event. The influence factors examined are perceived benefit, perceived risk, trust in the managing bodies, and pro-environmental orientation (i.e., new ecological paradigm). This study is based on cross-sectional data collected from two online nationwide surveys: one conducted in November 2009, before the nuclear accident, and the other in October 2011, after the accident. This study's target respondents were residents of Aomori, Miyagi, and Fukushima prefectures in the Tohoku region of Japan, as these areas were the epicenters of the Great East Japan Earthquake and the locations of nuclear power stations. After the accident, trust in the managing bodies was found to have a stronger influence on perceived risk, and pro-environmental orientation was found to have a stronger influence on trust in the managing bodies; however, perceived benefit had a weaker positive influence on public acceptance. We also discuss the theoretical and practical implications of these findings.

  19. Evaluation of Subsurface Radionuclide Transport at Commercial Nuclear Power Production Facilities

    NASA Astrophysics Data System (ADS)

    Rasmussen, T. C.; Bollinger, J. S.

    2006-05-01

    An American Nuclear Society (ANS) working group was recently established to revise ANSI/ANS-2.17, a standard for evaluating radionuclide transport in ground water at commercial nuclear power production (NPP) facilities. The working group consists of technical experts from the nuclear industry, Federal and State regulatory agencies, universities, DOE National Laboratories, and hydrogeologic consulting firms. ANS 2.17 was originally adopted in 1980, reaffirmed in 1990, but subsequently withdrawn in 2000 due to a lapse in the decadal concurrence process. The working group charge is to re-visit the lapsed standard, review the state-of-the-science and -practice, and develop a performance-based standard that provides guidelines for demonstrating the ability to detect, characterize, diagnose, quantify, and effectively mitigate accidental and routine subsurface releases of radionuclides from NPP facilities. The resulting consensus standard focuses on subsurface site characterization, monitoring, and modeling issues at NPP sites that will guide the siting and evaluation of radionuclide transport at both existing and proposed new NPP facilities. This presentation provides the technical background for developing the standard along with a description of its current status. Performance Assessment is the proposed framework for designing characterization, monitoring, and modeling programs that quantitatively evaluate release scenarios. Geographic Information Systems (GIS) are proposed for the archival and retrieval of spatially-explicit data, and will include real-time designators. New monitoring technologies are identified that may aid in the detection and characterization of releases. Remediation activities in response to detected releases should reflect, in part, the expected risk as defined using response thresholds. The presenters are actively soliciting technical documents and field application experiences which may contribute to the standard's technical bases and

  20. ϕ -meson production at forward/backward rapidity in high-energy nuclear collisions from a multiphase transport model

    NASA Astrophysics Data System (ADS)

    Ye, Y. J.; Chen, J. H.; Ma, Y. G.; Zhang, S.; Zhong, C.

    2016-04-01

    Within the framework of a multiphase transport model (AMPT), the ϕ -meson production is studied in d +Au collisions at √{sNN}=200 GeV in the forward (d -going, 1.2 transport scenario of the AMPT model underestimates the ϕ -meson production rate in comparison with the data. Detailed investigations including the rapidity, transverse momentum, and collision system size dependencies of ϕ -meson nuclear modification factor indicate that a combination of the initial-state effect and a follow-up parton cascade is required in the AMPT model to describe the data. Similar calculations are also present in p +Pb collisions at √{s NN}=5.02 TeV and p +p collisions at √{s NN}=2.76 TeV. The findings from a comparison of AMPT model study with the data are consistent with that at RHIC energy.

  1. Assessment of hydrologic transport of radionuclides from the Gasbuggy underground nuclear test site, New Mexico

    SciTech Connect

    Earman, S.; Chapman, J.; Andricevic, R.

    1996-09-01

    The U.S. Department of Energy (DOE) is operating an environmental restoration program to characterize, remediate, and close non-Nevada Test Site locations that were used for nuclear testing. Evaluation of radionuclide transport by groundwater from these sites is an important part of the preliminary risk analysis. These evaluations are undertaken to allow prioritization of the test areas in terms of risk, provide a quantitative basis for discussions with regulators and the public about future work at the sites, and provide a framework for assessing data needs to be filled by site characterization. The Gasbuggy site in northwestern New Mexico was the location of an underground detonation of a 29-kiloton nuclear device in 1967. The test took place in the Lewis Shale, approximately 182 m below the Ojo Alamo Sandstone, which is the aquifer closest to the detonation horizon. The conservative assumption was made that tritium was injected from the blast-created cavity into the Ojo Alamo Sandstone by the force of the explosion, via fractures created by the shot. Model results suggest that if radionuclides produced by the shot entered the Ojo Alamo, they are most likely contained within the area currently administered by DOE. The transport calculations are most sensitive to changes in the mean groundwater velocity, followed by the variance in hydraulic conductivity, the correlation scale of hydraulic conductivity, the transverse hydrodynamic dispersion coefficient, and uncertainty in the source size. This modeling was performed to investigate how the uncertainty in various physical parameters affects calculations of radionuclide transport at the Gasbuggy site, and to serve as a starting point for discussion regarding further investigation at the site; it was not intended to be a definitive simulation of migration pathways or radionuclide concentration values.

  2. Incidents at nuclear power plants caused by the human factor

    SciTech Connect

    Mashin, V. A.

    2012-09-15

    Psychological analysis of the causes of incorrect actions by personnel is discussed as presented in the report 'Methodological guidelines for analyzing the causes of incidents in the operation of nuclear power plants.' The types of incorrect actions and classification of the root causes of errors by personnel are analyzed. Recommendations are made for improvements in the psychological analysis of causes of incorrect actions by personnel.

  3. Nuclear pulse. I - Awakening to the chaos factor

    NASA Astrophysics Data System (ADS)

    Broad, W. J.

    1981-05-01

    The discovery of the significance of the high-voltage wave termed electromagnetic pulse (EMP), which occurs following the high-altitude detonation of a nuclear device, is discussed. The disruptions to the street lights, burglar alarms and circuit breakers of Hawaii caused by the detonation of a nuclear device 248 mi above Johnson Island in the Pacific in July, 1962 are described and attributed to the Compton electrons produced by the impact of gamma rays from the nuclear explosion on air in the upper atmosphere. It is pointed out, however, that at the time of the explosion, most communications systems were based on vacuum tube and electromechanical technology, which is about 10,000,000 times harder against EMP than integrated solid-state circuitry, and thus the threat posed by EMP to the power grid and communications capabilities was not apparent. Efforts undertaken to harden discrete (missile) and communications systems against EMP are outlined for the example of the Safeguard ABM system, and difficulties are pointed out. Soviet awareness of EMP is considered, and the discovery of vacuum tubes on board the state-of-the-art Foxbat MiG interceptor flown into Japan is noted as a possible indicator of this awareness. It is concluded that the problem of EMP will increase in significance as semiconductor electronics proliferates.

  4. Factors influencing mode of transport in older adolescents: a qualitative study

    PubMed Central

    2013-01-01

    Background Since a decline in activity levels occurs in adolescence, active transport could be important to increase daily physical activity in older adolescents (17–18 years). To promote active transport, it is necessary to be aware of the barriers and facilitators of this type of transport, but also of other transport modes. This study sought to uncover the factors influencing the choice of transport mode for short distance travel to various destinations in older adolescents using focus groups. Methods Thirty-two focus group volunteers (mean age of 17 ± 1.2 years) were recruited from the two final years of the secondary school in Antwerp (Belgium). Five focus groups were conducted (five to eight participants/group). Content analysis was performed using NVivo 9 software (QSR International). Grounded theory was used to derive categories and subcategories. Results Data were categorized in three main themes with several subcategories: personal factors (high autonomy, low costs and health), social factors (good social support) and physical environmental factors (short travel time, good access to transport modes and to facilities, good weather, an adapted built environment, perceived safety and ecology). Conclusions For older adolescents, the interplay between short travel time, high autonomy, good social support, low costs, good access to transport modes and facilities, and good weather was important for choosing active transport over other transport forms for travelling short distances to various destinations. Other well-known factors such as safety, ecology and health seemed not to have a big influence on their transport mode choice. PMID:23574974

  5. Learning about the nuclear symmetry energy through the lens of isospin transport

    NASA Astrophysics Data System (ADS)

    Desouza, Romualdo; Hudan, Sylvie; Brown, Kyle

    2014-03-01

    Examining nucleon transport between nuclei in intermediate energy heavy-ion collisions is an effective means to assess the density dependence of the nuclear symmetry energy. Overlap of the Fermi tails of the two nuclei as they collide provides a density gradient that drives nucleon transport. In addition, nucleon transport is driven by gradients in N/Z. Disentangling these two contributions provides a measure of the symmetry energy and its density dependence and requires a comparison of N/Z symmetric and asymmetric systems. To address this question we have examined semi-peripheral collisions of 64Zn ions with 64Zn, 209Bi, and 27Al targets at Elab 45 MeV/A. The projectile-like fragment emerging from these collisions frequently undergoes binary decay in a dynamical fission process. By using the rotation of the projectile-like fragment as a clock, it is deduced that N/Z equilibration persists up to 1200 fm/c. As prior measurements were restricted to timescales of less than 100 fm/c, this approach represents a dramatic improvement in the sensitivity to long timescales. This work is supported by the U.S. DOE under Grant No. DEFG02-88ER-40404.

  6. The adiabatic limit of the exact factorization of the electron-nuclear wave function.

    PubMed

    Eich, F G; Agostini, Federica

    2016-08-01

    We propose a procedure to analyze the relation between the exact factorization of the electron-nuclear wave function and the Born-Oppenheimer approximation. We define the adiabatic limit as the limit of infinite nuclear mass. To this end, we introduce a unit system that singles out the dependence on the electron-nuclear mass ratio of each term appearing in the equations of the exact factorization. We observe how non-adiabatic effects induced by the coupling to the nuclear motion affect electronic properties and we analyze the leading term, connecting it to the classical nuclear momentum. Its dependence on the mass ratio is tested numerically on a model of proton-coupled electron transfer in different non-adiabatic regimes. PMID:27497542

  7. The adiabatic limit of the exact factorization of the electron-nuclear wave function

    NASA Astrophysics Data System (ADS)

    Eich, F. G.; Agostini, Federica

    2016-08-01

    We propose a procedure to analyze the relation between the exact factorization of the electron-nuclear wave function and the Born-Oppenheimer approximation. We define the adiabatic limit as the limit of infinite nuclear mass. To this end, we introduce a unit system that singles out the dependence on the electron-nuclear mass ratio of each term appearing in the equations of the exact factorization. We observe how non-adiabatic effects induced by the coupling to the nuclear motion affect electronic properties and we analyze the leading term, connecting it to the classical nuclear momentum. Its dependence on the mass ratio is tested numerically on a model of proton-coupled electron transfer in different non-adiabatic regimes.

  8. Measurements of air pollution emission factors for marine transportation

    NASA Astrophysics Data System (ADS)

    Alföldy, B.; Balzani Lööv, J.; Lagler, F.; Mellqvist, J.; Berg, N.; Beecken, J.; Weststrate, H.; Duyzer, J.; Bencs, L.; Horemans, B.; Cavalli, F.; Putaud, J.-P.; Janssens-Maenhout, G.; Pintér Csordás, A.; Van Grieken, R.; Borowiak, A.; Hjorth, J.

    2012-12-01

    The chemical composition of the plumes of seagoing ships was investigated during a two weeks long measurement campaign in the port of Rotterdam, Hoek van Holland, The Netherlands, in September 2009. Altogether, 497 ships were monitored and a statistical evaluation of emission factors (g kg-1 fuel) was provided. The concerned main atmospheric components were SO2, NO2, NOx and the aerosol particle number. In addition, the elemental and water-soluble ionic composition of the emitted particulate matter was determined. Emission factors were expressed as a function of ship type, power and crankshaft rotational speed. The average SO2 emission factor was found to be roughly half of what is allowed in sulphur emission control areas (16 vs. 30 g kg-1 fuel), and exceedances of this limit were rarely registered. A significant linear relationship was observed between the SO2 and particle number emission factor. The intercept of the regression line, 0.5 × 1016 (kg fuel)-1, gives the average number of particles formed during the burning of 1 kg zero sulphur content fuel, while the slope, 2 × 1018, provides the average number of particles formed with 1 kg sulphur burnt with the fuel. Water-soluble ionic composition analysis of the aerosol samples from the plumes showed that ~144 g of particulate sulphate was emitted from 1 kg sulphur burnt with the fuel. The mass median diameter of sulphate particles estimated from the measurements was ~42 nm.

  9. Modeling of molecular and particulate transport in dry spent nuclear fuel canisters

    NASA Astrophysics Data System (ADS)

    Casella, Andrew M.

    2007-09-01

    The transportation and storage of spent nuclear fuel is one of the prominent issues facing the commercial nuclear industry today, as there is still no general consensus regarding the near- and long-term strategy for managing the back-end of the nuclear fuel cycle. The debate continues over whether the fuel cycle should remain open, in which case spent fuel will be stored at on-site reactor facilities, interim facilities, or a geologic repository; or if the fuel cycle should be closed, in which case spent fuel will be recycled. Currently, commercial spent nuclear fuel is stored at on-site reactor facilities either in pools or in dry storage containers. Increasingly, spent fuel is being moved to dry storage containers due to decreased costs relative to pools. As the number of dry spent fuel containers increases and the roles they play in the nuclear fuel cycle increase, more regulations will be enacted to ensure that they function properly. Accordingly, they will have to be carefully analyzed for normal conditions, as well as any off-normal conditions of concern. This thesis addresses the phenomena associated with one such concern; the formation of a microscopic through-wall breach in a dry storage container. Particular emphasis is placed on the depressurization of the canister, release of radioactivity, and plugging of the breach due to deposition of suspended particulates. The depressurization of a dry storage container upon the formation of a breach depends on the temperature and quantity of the fill gas, the pressure differential across the breach, and the size of the breach. The first model constructed in this thesis is capable of determining the depressurization time for a breached container as long as the associated parameters just identified allow for laminar flow through the breach. The parameters can be manipulated to quantitatively determine their effect on depressurization. This model is expanded to account for the presence of suspended particles. If

  10. Edoxaban transport via P-glycoprotein is a key factor for the drug's disposition.

    PubMed

    Mikkaichi, Tsuyoshi; Yoshigae, Yasushi; Masumoto, Hiroshi; Imaoka, Tomoki; Rozehnal, Veronika; Fischer, Thomas; Okudaira, Noriko; Izumi, Takashi

    2014-04-01

    Edoxaban (the free base of DU-176b), an oral direct factor Xa inhibitor, is mainly excreted unchanged into urine and feces. Because active membrane transport processes such as active renal secretion, biliary excretion, and/or intestinal secretion, and the incomplete absorption of edoxaban after oral administration have been observed, the involvement of drug transporters in the disposition of edoxaban was investigated. Using a bidirectional transport assay in human colon adenocarcinoma Caco-2 cell monolayers, we observed the vectorial transport of [(14)C]edoxaban, which was completely inhibited by verapamil, a strong P-glycoprotein (P-gp) inhibitor. In an in vivo study, an increased distribution of edoxaban to the brain was observed in Mdr1a/1b knockout mice when compared with wild-type mice, indicating that edoxaban is a substrate for P-gp. However, there have been no observations of significant transport of edoxaban by renal or hepatic uptake transporters, organic anion transporter (OAT)1, OAT3, organic cation transporter (OCT)2, or organic anion transporting polypeptide (OATP)1B1. Edoxaban exhibited no remarkable inhibition of OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, or P-gp up to 30 μM; therefore, the risk of clinical drug-drug interactions due to any edoxaban-related transporter inhibition seems to be negligible. Our results demonstrate that edoxaban is a substrate of P-gp but not of other major uptake transporters tested. Because metabolism is a minor contributor to the total clearance of edoxaban and strong P-gp inhibitors clearly impact edoxaban transport, the P-gp transport system is a key factor for edoxaban's disposition.

  11. Review of key factors controlling engineered nanoparticle transport in porous media.

    PubMed

    Wang, Mei; Gao, Bin; Tang, Deshan

    2016-11-15

    Nanotechnology, an emerging technology, has witnessed rapid development in production and application. Engineered nanomaterials revolutionize the industry due to their unique structure and superior performance. The release of engineered nanoparticles (ENPs) into the environment, however, may pose risks to the environment and public health. To advance current understanding of environmental behaviors of ENPs, this work provides an introductory overview of ENP fate and transport in porous media. It systematically reviews the key factors controlling their fate and transport in porous media. It first provides a brief overview of common ENPs in the environment and their sources. The key factors that govern ENP transport in porous media are then categorized into three groups: (1) nature of ENPs affecting their transport in porous media, (2) nature of porous media affecting ENP transport, and (3) nature of flow affecting ENP transport in porous media. In each group, findings in recent literature on the specific governing factors of ENP transport in porous media are discussed in details. Finally, this work concludes with remarks on the importance of ENP transport in porous media and directions for future research. PMID:27427890

  12. Transcription factors that mediate epithelial–mesenchymal transition lead to multidrug resistance by upregulating ABC transporters

    PubMed Central

    Saxena, M; Stephens, M A; Pathak, H; Rangarajan, A

    2011-01-01

    Development of multidrug resistance (MDR) is a major deterrent in the effective treatment of metastatic cancers by chemotherapy. Even though MDR and cancer invasiveness have been correlated, the molecular basis of this link remains obscure. We show here that treatment with chemotherapeutic drugs increases the expression of several ATP binding cassette transporters (ABC transporters) associated with MDR, as well as epithelial–mesenchymal transition (EMT) markers, selectively in invasive breast cancer cells, but not in immortalized or non-invasive cells. Interestingly, the mere induction of an EMT in immortalized and non-invasive cell lines increased their expression of ABC transporters, migration, invasion, and drug resistance. Conversely, reversal of EMT in invasive cells by downregulating EMT-inducing transcription factors reduced their expression of ABC transporters, invasion, and rendered them more chemosensitive. Mechanistically, we demonstrate that the promoters of ABC transporters carry several binding sites for EMT-inducing transcription factors, and overexpression of Twist, Snail, and FOXC2 increases the promoter activity of ABC transporters. Furthermore, chromatin immunoprecipitation studies revealed that Twist binds directly to the E-box elements of ABC transporters. Thus, our study identifies EMT inducers as novel regulators of ABC transporters, thereby providing molecular insights into the long-standing association between invasiveness and MDR. Targeting EMT transcription factors could hence serve as novel strategies to curb both metastasis and the associated drug resistance. PMID:21734725

  13. Effects of the MacArthur Maze Fire and Roadway Collapse on a Spent Nuclear Fuel Transportation Package

    SciTech Connect

    Bajwa, Christopher S.; Easton, Earl P.; Adkins, Harold E.; Cuta, Judith M.; Klymyshyn, Nicholas A.; Suffield, Sarah R.

    2011-03-03

    In 2007, a severe transportation accident occurred near Oakland, California, on a section of Interstate 880 known as the "MacArthur Maze," involving a tractor trailer carrying gasoline which impacted an overpass support column and burst into flames. The subsequent fire caused the collapse of portions of the Interstate 580 overpass onto the remains of the tractor-trailer in less than 20 minutes, due to a reduction of strength in the structural steel exposed to the fire. The US Nuclear Regulatory Commission is in the process of examining the impacts of this accident on the performance of a spent nuclear fuel transportation package, using detailed analysis models, in order to determine the potential regulatory implications related to the safe transport of spent nuclear fuel in the United States. This paper will provide a summary of this ongoing effort and present some preliminary results and conclusions.

  14. The MacArthur Maze Fire and Roadway Collapse: A "Worst Case Scenario" for Spent Nuclear Fuel Transportation?

    SciTech Connect

    Bajwa, Christopher S.; Easton, Earl P.; Adkins, Harold E.; Cuta, Judith M.; Klymyshyn, Nicholas A.; Suffield, Sarah R.

    2012-07-06

    In 2007, a severe transportation accident occurred near Oakland, California, at the interchange known as the "MacArthur Maze." The accident involved a double tanker truck of gasoline overturning and bursting into flames. The subsequent fire reduced the strength of the supporting steel structure of an overhead interstate roadway causing the collapse of portions of that overpass onto the lower roadway in less than 20 minutes. The US Nuclear Regulatory Commission has analyzed what might have happened had a spent nuclear fuel transportation package been involved in this accident, to determine if there are any potential regulatory implications of this accident to the safe transport of spent nuclear fuel in the United States. This paper provides a summary of this effort, presents preliminary results and conclusions, and discusses future work related to the NRC's analysis of the consequences of this type of severe accident.

  15. Perceived environmental and personal factors associated with walking and cycling for transportation in Taiwanese adults.

    PubMed

    Liao, Yung; Wang, I-Ting; Hsu, Hsiu-Hua; Chang, Shao-Hsi

    2015-02-13

    This study examined perceived environmental and personal factors associated with walking and cycling as means of transportation for Taiwanese adults. A random-digit-dialing telephone-based cross-sectional survey was conducted with Taiwanese adults aged 20 to 64 years. Data on time spent walking and cycling for transportation and perceptions of neighborhood environment and personal characteristics were obtained from 1065 adults by using the International Physical Activity Questionnaire-long version and its environmental module. Adjusted binary logistic regression was performed. The results showed that, after adjusting potential confounders, common and different personal and perceived environmental factors were associated with walking and cycling for transportation. For common personal factors, adults who had employment were less likely to engage in 150 min of walking per week (odds ratio [OR] = 0.41; 95% confidence interval (CI): 0.27-0.62) and to use cycling as a means of transportation (OR = 0.51; 95% CI: 0.32-0.79). For common perceived environmental factors, adults who perceived good connectivity of streets were more likely to walk (OR = 1.95; 95% CI: 1.20-3.16) and cycle (OR = 2.02; 95% CI: 1.16-3.54) for transportation. Targeting employed adults and improving the connectivity of streets should be a priority for developing transport policies and intervention strategies to promote active transportation.

  16. Hydrothermal Alteration of Glass from Underground Nuclear Tests: Formation and Transport of Pu-clay Colloids at the Nevada National Security Site

    SciTech Connect

    Zavarin, M.; Zhao, P.; Joseph, C.; Begg, J.; Boggs, M.; Dai, Z.; Kersting, A. B.

    2015-05-27

    The testing of nuclear weapons at the Nevada National Security Site (NNSS), formerly the Nevada Test Site (NTS), has led to the deposition of substantial quantities of plutonium into the environment. Approximately 2.8 metric tons (3.1×104 TBq) of Pu were deposited in the NNSS subsurface as a result of underground nuclear testing. While 3H is the most abundant anthropogenic radionuclide deposited in the NNSS subsurface (4.7×106 TBq), plutonium is the most abundant from a molar standpoint. The only radioactive elements in greater molar abundance are the naturally occurring K, Th, and U isotopes. 239Pu and 240Pu represent the majority of alpha-emitting Pu isotopes. The extreme temperatures associated with underground nuclear tests and the refractory nature of Pu results in most of the Pu (98%) being sequestered in melted rock, referred to as nuclear melt glass (Iaea, 1998). As a result, Pu release to groundwater is controlled, in large part, by the leaching (or dissolution) of nuclear melt glass over time. The factors affecting glass dissolution rates have been studied extensively. The dissolution of Pu-containing borosilicate nuclear waste glasses at 90ºC has been shown to lead to the formation of dioctahedral smectite colloids. Colloid-facilitated transport of Pu at the NNSS has been observed. Recent groundwater samples collected from a number of contaminated wells have yielded a wide range of Pu concentrations from 0.00022 to 2.0 Bq/L. While Pu concentrations tend to fall below the Maximum Contaminant Level (MCL) established by the Environmental Protection Agency (EPA) for drinking water (0.56 Bq/L), we do not yet understand what factors limit the Pu concentration or its transport behavior. To quantify the upper limit of Pu concentrations produced as a result of melt glass dissolution and determine the nature of colloids and Pu associations, we performed a 3 year nuclear melt glass dissolution experiment

  17. Best Practices for Finite Element Analysis of Spent Nuclear Fuel Transfer, Storage, and Transportation Systems

    SciTech Connect

    Bajwa, Christopher S.; Piotter, Jason; Cuta, Judith M.; Adkins, Harold E.; Klymyshyn, Nicholas A.; Fort, James A.; Suffield, Sarah R.

    2010-08-11

    Storage casks and transportation packages for spent nuclear fuel (SNF) are designed to confine SNF in sealed canisters or casks, provide structural integrity during accidents, and remove decay through a storage or transportation overpack. The transfer, storage, and transportation of SNF in dry storage casks and transport packages is regulated under 10 CFR Part 72 and 10 CFR Part 71, respectively. Finite Element Analysis (FEA) is used with increasing frequency in Safety Analysis Reports and other regulatory technical evaluations related to SNF casks and packages and their associated systems. Advances in computing power have made increasingly sophisticated FEA models more feasible, and as a result, the need for careful review of such models has also increased. This paper identifies best practice recommendations that stem from recent NRC review experience. The scope covers issues common to all commercially available FEA software, and the recommendations are applicable to any FEA software package. Three specific topics are addressed: general FEA practices, issues specific to thermal analyses, and issues specific to structural analyses. General FEA practices covers appropriate documentation of the model and results, which is important for an efficient review process. The thermal analysis best practices are related to cask analysis for steady state conditions and transient scenarios. The structural analysis best practices are related to the analysis of casks and associated payload during standard handling and drop scenarios. The best practices described in this paper are intended to identify FEA modeling issues and provide insights that can help minimize associated uncertainties and errors, in order to facilitate the NRC licensing review process.

  18. Measurement and modelling of reactive transport in geological barriers for nuclear waste containment.

    PubMed

    Xiong, Qingrong; Joseph, Claudia; Schmeide, Katja; Jivkov, Andrey P

    2015-11-11

    Compacted clays are considered as excellent candidates for barriers to radionuclide transport in future repositories for nuclear waste due to their very low hydraulic permeability. Diffusion is the dominant transport mechanism, controlled by a nano-scale pore system. Assessment of the clays' long-term containment function requires adequate modelling of such pore systems and their evolution. Existing characterisation techniques do not provide complete pore space information for effective modelling, such as pore and throat size distributions and connectivity. Special network models for reactive transport are proposed here using the complimentary character of the pore space and the solid phase. This balances the insufficient characterisation information and provides the means for future mechanical-physical-chemical coupling. The anisotropy and heterogeneity of clays is represented using different length parameters and percentage of pores in different directions. Resulting networks are described as mathematical graphs with efficient discrete calculus formulation of transport. Opalinus Clay (OPA) is chosen as an example. Experimental data for the tritiated water (HTO) and U(vi) diffusion through OPA are presented. Calculated diffusion coefficients of HTO and uranium species are within the ranges of the experimentally determined data in different clay directions. This verifies the proposed pore network model and validates that uranium complexes are diffusing as neutral species in OPA. In the case of U(vi) diffusion the method is extended to account for sorption and convection. Rather than changing pore radii by coarse grained mathematical formula, physical sorption is simulated in each pore, which is more accurate and realistic. PMID:26524292

  19. Allowable shipment frequencies for the transport of toxic gases near nuclear power plants

    SciTech Connect

    Bennett, D.E.; Heath, D.C.

    1982-10-01

    One part of the safety analysis of offsite hazards for a nuclear power plant is consideration of accidents which could release toxic gases or vapors and thus jeopardize plant safety through incapacitation of the control room operators. The purpose of this work is to provide generic, bounding estimates of the maximum allowable shipping frequencies for the transport of a chemical near the plant, such that the regulatory criteria for the protection of the operators are met. A probabilistic methodology was developed and then applied to the truck and rail transport of an example chemical, chlorine. The current regulatory criteria are discussed in detail. For this study, a maximum allowable probability of occurrence of operator incapacitation of 10/sup -5/ per year was used in the example calculation for each mode of transport. Comprehensive tables of conditional probabilities are presented. Maximum allowable ahipping frequencies are then derived. These frequencies could be used as part of a generic, bounding criterion for the screening of toxic hazards safety analyses. Unless a transport survey assures shipping frequencies within 8 km of the plant on the order of or lower than 4/week for rail or 35/week for truck, the contol room should be isolatable and the shipping frequency then determines the degree of isolation needed. The need for isolation implies the need for toxic chemical detection at the air intake.For a self-detection case in which the smell threshold is significantly lower than the incapacitation threshold and the control room is isolatable, the corresponding trequencies are 11/week for rail or 115/week for truck. Self-contained breathing equipment is assumed to be used after 5 minutes.

  20. Factors Influencing Observed Tillage Impacts on Herbicide Transport

    NASA Astrophysics Data System (ADS)

    Pappas, E. A.; Huang, C.; Smith, D. R.

    2009-04-01

    The widespread use and potential human health effects of the herbicides atrazine and glyphosate have generated interest in establishing how no-tillage impacts loading of these herbicides to runoff water in comparison to other tillage practices. In this study, potentially confounding factos such as time in tillage practice and type and distribution of residue cover, are weighed against inherent tillage impacts to soil structure in terms of relative effects on herbicide transport with runoff water. In this study, two small watersheds (one in no-till (NT) and one rotational till (RT)) were monitored during the first three years since conversion of the RT watershed from NT. In addition, rainfall simulation was applied to plots within each watershed during the first, third, and fifth years since the conversion. Runoff atrazine and glyphosate losses from RT areas were compared to losses from NT areas as a ratio of RT:NT. Results indicate a trend of increasing RT:NT value with time in tillage. Watershed monitoring indicated greater herbicide loading to runoff water from the NT watershed than the RT watershed during the first year since RT conversion, but this relationship reversed by the third year since conversion to RT. In addition, rainfall simulations were performed on small boxes of NT or RT soil having varying types and levels of residue cover in an attempt to isolate residue cover effects from true tillage effects.

  1. MODELING OF THE GROUNDWATER TRANSPORT AROUND A DEEP BOREHOLE NUCLEAR WASTE REPOSITORY

    SciTech Connect

    N. Lubchenko; M. Rodríguez-Buño; E.A. Bates; R. Podgorney; E. Baglietto; J. Buongiorno; M.J. Driscoll

    2015-04-01

    The concept of disposal of high-level nuclear waste in deep boreholes drilled into crystalline bedrock is gaining renewed interest and consideration as a viable mined repository alternative. A large amount of work on conceptual borehole design and preliminary performance assessment has been performed by researchers at MIT, Sandia National Laboratories, SKB (Sweden), and others. Much of this work relied on analytical derivations or, in a few cases, on weakly coupled models of heat, water, and radionuclide transport in the rock. Detailed numerical models are necessary to account for the large heterogeneity of properties (e.g., permeability and salinity vs. depth, diffusion coefficients, etc.) that would be observed at potential borehole disposal sites. A derivation of the FALCON code (Fracturing And Liquid CONvection) was used for the thermal-hydrologic modeling. This code solves the transport equations in porous media in a fully coupled way. The application leverages the flexibility and strengths of the MOOSE framework, developed by Idaho National Laboratory. The current version simulates heat, fluid, and chemical species transport in a fully coupled way allowing the rigorous evaluation of candidate repository site performance. This paper mostly focuses on the modeling of a deep borehole repository under realistic conditions, including modeling of a finite array of boreholes surrounded by undisturbed rock. The decay heat generated by the canisters diffuses into the host rock. Water heating can potentially lead to convection on the scale of thousands of years after the emplacement of the fuel. This convection is tightly coupled to the transport of the dissolved salt, which can suppress convection and reduce the release of the radioactive materials to the aquifer. The purpose of this work has been to evaluate the importance of the borehole array spacing and find the conditions under which convective transport can be ruled out as a radionuclide transport mechanism

  2. Nuclear Energy R&D Imperative 3: Enable a Transition Away from Fossil Fuel in the Transportation and Industrial Sectors

    SciTech Connect

    David Petti; J. Stephen Herring

    2010-03-01

    As described in the Department of Energy Office of Nuclear Energy’s Nuclear Energy R&D Roadmap, nuclear energy can play a significant role in supplying energy for a growing economy while reducing both our dependence on foreign energy supplies and emissions from the burning of fossil fuels. The industrial and transportation sectors are responsible for more than half of the greenhouse gas emissions in the U.S., and imported oil supplies 70% of the energy used in the transportation sector. It is therefore important to examine the various ways nuclear energy can facilitate a transition away from fossil fuels to secure environmentally sustainable production and use of energy in the transportation and manufacturing industry sectors. Imperative 3 of the Nuclear Energy R&D Roadmap, entitled “Enable a Transition Away from Fossil Fuels by Producing Process Heat for use in the Transportation and Industrial Sectors”, addresses this need. This document presents an Implementation Plan for R&D efforts related to this imperative. The expanded use of nuclear energy beyond the electrical grid will contribute significantly to overcoming the three inter-linked energy challenges facing U.S. industry: the rising and volatile prices for premium fossil fuels such as oil and natural gas, dependence on foreign sources for these fuels, and the risks of climate change resulting from carbon emissions. Nuclear energy could be used in the industrial and transportation sectors to: • Generate high temperature process heat and electricity to serve industrial needs including the production of chemical feedstocks for use in manufacturing premium fuels and fertilizer products, • Produce hydrogen for industrial processes and transportation fuels, and • Provide clean water for human consumption by desalination and promote wastewater treatment using low-grade nuclear heat as a useful additional benefit. Opening new avenues for nuclear energy will significantly enhance our nation’s energy

  3. Factors affecting the retirement of commercial transport jet aircraft

    NASA Technical Reports Server (NTRS)

    Spencer, F. A.

    1979-01-01

    The historical background of the technology and economics of aircraft replacement and retirement in the prejet era is reviewed in order to determine whether useful insights can be obtained applicable to the jet era. Significant differences between the two periods are noted. New factors are identified and examined. Topics discussed include concern over current policies regarding deregulation, regulatory reform, and retroactive noise regulations; financing and compliance legislation; aging; economic environment and inflation; technological progress; fuel efficiency and cost; and a financial perspective of replacement decisions.

  4. Transforming growth factor β signaling upregulates the expression of human GDP-fucose transporter by activating transcription factor Sp1.

    PubMed

    Xu, Yu-Xin; Ma, Anna; Liu, Li

    2013-01-01

    GDP-fucose transporter plays a crucial role in fucosylation of glycoproteins by providing activated fucose donor, GDP-fucose, for fucosyltransferases in the lumen of the Golgi apparatus. Fucose-containing glycans are involved in many biological processes, which are essential for growth and development. Mutations in the GDP-fucose transporter gene cause leukocyte adhesion deficiency syndrome II, a disease characterized by slow growth, mental retardation and immunodeficiency. However, no information is available regarding its transcriptional regulation. Here, by using human cells, we show that TGF-β1 specifically induces the GDP-fucose transporter expression, but not other transporters tested such as CMP-sialic acid transporter, suggesting a diversity of regulatory pathways for the expression of these transporters. The regulatory elements that are responsive to the TGF-β1 stimulation are present in the region between bp -330 and -268 in the GDP-fucose transporter promoter. We found that this region contains two identical octamer GC-rich motifs (GGGGCGTG) that were demonstrated to be essential for the transporter expression. We also show that the transcription factor Sp1 specifically binds to the GC-rich motifs in vitro and Sp1 coupled with phospho-Smad2 is associated with the promoter region covering the Sp1-binding motifs in vivo using chromatin immunoprecipitation (ChIP) assays. In addition, we further confirmed that Sp1 is essential for the GDP-fucose transporter expression stimulated by TGF-β1 using a luciferase reporter system. These results highlight the role of TGF-β signaling in regulation of the GDP-fucose transporter expression via activating Sp1. This is the first transcriptional study for any nucleotide sugar transporters that have been identified so far. Notably, TGF-β1 receptor itself is known to be modified by fucosylation. Given the essential role of GDP-fucose transporter in fucosylation, the finding that TGF-β1 stimulates the expression of

  5. Pulsed-field gradient nuclear magnetic resonance study of transport properties of fluid catalytic cracking catalysts.

    PubMed

    Kortunov, P; Vasenkov, S; Kärger, J; Fé Elía, M; Perez, M; Stöcker, M; Papadopoulos, G K; Theodorou, D; Drescher, B; McElhiney, G; Bernauer, B; Krystl, V; Kocirik, M; Zikanova, A; Jirglova, H; Berger, C; Gläser, R; Weitkamp, J; Hansen, E W

    2005-02-01

    Pulsed-field gradient nuclear magnetic resonance (PFG NMR) has been applied to study molecular diffusion in industrial fluid catalytic cracking (FCC) catalysts and in USY zeolite for a broad range of molecular displacements and temperatures. The results of this study have been used to elucidate the relevance of molecular transport on various displacements for the rate of molecular exchange between catalyst particles and their surroundings. It turned out that this rate, which may determine the overall rate and selectivity of FCC process, is primarily related to the diffusion mode associated with displacements larger than the size of zeolite crystals located in the particles but smaller than the size of the particles. This conclusion has been confirmed by comparative studies of the catalytic performance of different FCC catalysts.

  6. Importance of mammalian nuclear-envelope nucleoside triphosphatase in nucleo-cytoplasmic transport of ribonucleoproteins.

    PubMed Central

    Agutter, P S; McCaldin, B; McArdle, H J

    1979-01-01

    The nucleoside triphosphate-stimulated efflux of RNA from isolated nuclei was studied under a range of conditions, and the effects of these conditions on the process were compared with the properties of the nucleoside triphosphatase located in the pore complex. A marked similarity between the rate of efflux and the rate of nucleoside triphosphate hydrolysis was apparent, in terms of substrate specificity, sensitivity to treatment with insolubilized trypsin, kinetics and the effects of increased ionic strength and of many inhibitors. These results are taken, in view of earlier evidence, to suggest that the activity of the nucleoside triphosphatase is a prerequisite for nucleo-cytoplasmic RNA transport in vivo. There are some indications that the nuclear-envelope lipid is also involved in regulating the efflux process. PMID:229828

  7. Importance of mammalian nuclear-envelope nucleoside triphosphatase in nucleo-cytoplasmic transport of ribonucleoproteins.

    PubMed

    Agutter, P S; McCaldin, B; McArdle, H J

    1979-09-15

    The nucleoside triphosphate-stimulated efflux of RNA from isolated nuclei was studied under a range of conditions, and the effects of these conditions on the process were compared with the properties of the nucleoside triphosphatase located in the pore complex. A marked similarity between the rate of efflux and the rate of nucleoside triphosphate hydrolysis was apparent, in terms of substrate specificity, sensitivity to treatment with insolubilized trypsin, kinetics and the effects of increased ionic strength and of many inhibitors. These results are taken, in view of earlier evidence, to suggest that the activity of the nucleoside triphosphatase is a prerequisite for nucleo-cytoplasmic RNA transport in vivo. There are some indications that the nuclear-envelope lipid is also involved in regulating the efflux process.

  8. Source-to-sink transport of sugar and regulation by environmental factors

    PubMed Central

    Lemoine, Remi; Camera, Sylvain La; Atanassova, Rossitza; Dédaldéchamp, Fabienne; Allario, Thierry; Pourtau, Nathalie; Bonnemain, Jean-Louis; Laloi, Maryse; Coutos-Thévenot, Pierre; Maurousset, Laurence; Faucher, Mireille; Girousse, Christine; Lemonnier, Pauline; Parrilla, Jonathan; Durand, Mickael

    2013-01-01

    Source-to-sink transport of sugar is one of the major determinants of plant growth and relies on the efficient and controlled distribution of sucrose (and some other sugars such as raffinose and polyols) across plant organs through the phloem. However, sugar transport through the phloem can be affected by many environmental factors that alter source/sink relationships. In this paper, we summarize current knowledge about the phloem transport mechanisms and review the effects of several abiotic (water and salt stress, mineral deficiency, CO2, light, temperature, air, and soil pollutants) and biotic (mutualistic and pathogenic microbes, viruses, aphids, and parasitic plants) factors. Concerning abiotic constraints, alteration of the distribution of sugar among sinks is often reported, with some sinks as roots favored in case of mineral deficiency. Many of these constraints impair the transport function of the phloem but the exact mechanisms are far from being completely known. Phloem integrity can be disrupted (e.g., by callose deposition) and under certain conditions, phloem transport is affected, earlier than photosynthesis. Photosynthesis inhibition could result from the increase in sugar concentration due to phloem transport decrease. Biotic interactions (aphids, fungi, viruses…) also affect crop plant productivity. Recent breakthroughs have identified some of the sugar transporters involved in these interactions on the host and pathogen sides. The different data are discussed in relation to the phloem transport pathways. When possible, the link with current knowledge on the pathways at the molecular level will be highlighted. PMID:23898339

  9. Human factors studies of control configurations for advanced transport aircraft

    NASA Technical Reports Server (NTRS)

    Snyder, Harry L.; Monty, Robert W.; Old, Joe

    1985-01-01

    This research investigated the threshold levels of display luminance contrast which were required to interpret static, achromatic, integrated displays of primary flight information. A four-factor within-subjects design was used to investigate the influences of type of flight variable information, the level of ambient illumination, the type of control input, and the size of the display symbology on the setting of these interpretability thresholds. A three-alternative forced choice paradigm was used in conjunction with the method of adjustments to obtain a measure of the upper limen of display luminance contrast needed to interpret a complex display of primary flight information. The pattern of results and the absolute magnitudes of the luminance contrast settings were found to be in good agreement with previously reported data from psychophysical investigations of display luminance contrast requirements.

  10. Spallation neutron production and the current intra-nuclear cascade and transport codes

    NASA Astrophysics Data System (ADS)

    Filges, D.; Goldenbaum, F.; Enke, M.; Galin, J.; Herbach, C.-M.; Hilscher, D.; Jahnke, U.; Letourneau, A.; Lott, B.; Neef, R.-D.; Nünighoff, K.; Paul, N.; Péghaire, A.; Pienkowski, L.; Schaal, H.; Schröder, U.; Sterzenbach, G.; Tietze, A.; Tishchenko, V.; Toke, J.; Wohlmuther, M.

    A recent renascent interest in energetic proton-induced production of neutrons originates largely from the inception of projects for target stations of intense spallation neutron sources, like the planned European Spallation Source (ESS), accelerator-driven nuclear reactors, nuclear waste transmutation, and also from the application for radioactive beams. In the framework of such a neutron production, of major importance is the search for ways for the most efficient conversion of the primary beam energy into neutron production. Although the issue has been quite successfully addressed experimentally by varying the incident proton energy for various target materials and by covering a huge collection of different target geometries --providing an exhaustive matrix of benchmark data-- the ultimate challenge is to increase the predictive power of transport codes currently on the market. To scrutinize these codes, calculations of reaction cross-sections, hadronic interaction lengths, average neutron multiplicities, neutron multiplicity and energy distributions, and the development of hadronic showers are confronted with recent experimental data of the NESSI collaboration. Program packages like HERMES, LCS or MCNPX master the prevision of reaction cross-sections, hadronic interaction lengths, averaged neutron multiplicities and neutron multiplicity distributions in thick and thin targets for a wide spectrum of incident proton energies, geometrical shapes and materials of the target generally within less than 10% deviation, while production cross-section measurements for light charged particles on thin targets point out that appreciable distinctions exist within these models.

  11. KPNA7, a nuclear transport receptor, promotes malignant properties of pancreatic cancer cells in vitro

    SciTech Connect

    Laurila, Eeva; Vuorinen, Elisa; Savinainen, Kimmo; Rauhala, Hanna; Kallioniemi, Anne

    2014-03-10

    Pancreatic cancer is an aggressive malignancy and one of the leading causes of cancer deaths. The high mortality rate is mostly due to the lack of appropriate tools for early detection of the disease and a shortage of effective therapies. We have previously shown that karyopherin alpha 7 (KPNA7), the newest member of the alpha karyopherin family of nuclear import receptors, is frequently amplified and overexpressed in pancreatic cancer. Here, we report that KPNA7 expression is absent in practically all normal human adult tissues but elevated in several pancreatic cancer cell lines. Inhibition of KPNA7 expression in AsPC-1 and Hs700T pancreatic cancer cells led to a reduction in cell growth and decreased anchorage independent growth, as well as increased autophagy. The cell growth effects were accompanied by an induction of the cell cycle regulator p21 and a G1 arrest of the cell cycle. Interestingly, the p21 induction was caused by increased mRNA synthesis and not defective nuclear transport. These data strongly demonstrate that KPNA7 silencing inhibits the malignant properties of pancreatic cancer cells in vitro and thereby provide the first evidence on the functional role for KPNA7 in human cancer. - Highlights: • KPNA7 expression is elevated in several pancreatic cancer cell lines. • KPNA7 silencing in high expressing cancer cells leads to growth inhibition. • The cell growth reduction is associated with p21 induction and G1 arrest. • KPNA7 silencing is also accompanied with increased autophagy.

  12. Transcriptional regulation of the human Liver X Receptor α gene by Hepatocyte Nuclear Factor 4α.

    PubMed

    Theofilatos, Dimitris; Anestis, Aristomenis; Hashimoto, Koshi; Kardassis, Dimitris

    2016-01-15

    Liver X Receptors (LXRs) are sterol-activated transcription factors that play major roles in cellular cholesterol homeostasis, HDL biogenesis and reverse cholesterol transport. The aim of the present study was to investigate the mechanisms that control the expression of the human LXRα gene in hepatic cells. A series of reporter plasmids containing consecutive 5' deletions of the hLXRα promoter upstream of the luciferase gene were constructed and the activity of each construct was measured in HepG2 cells. This analysis showed that the activity of the human LXRα promoter was significantly reduced by deleting the -111 to -42 region suggesting the presence of positive regulatory elements in this short proximal fragment. Bioinformatics data including motif search and ChIP-Seq revealed the presence of a potential binding motif for Hepatocyte Nuclear Factor 4 α (HNF-4α) in this area. Overexpression of HNF-4α in HEK 293T cells increased the expression of all LXRα promoter constructs except -42/+384. In line, silencing the expression of endogenous HNF-4α in HepG2 cells was associated with reduced LXRα protein levels and reduced activity of the -111/+384 LXRα promoter but not of the -42/+384 promoter. Using ChiP assays in HepG2 cells combined with DNAP assays we mapped the novel HNF-4α specific binding motif (H4-SBM) in the -50 to -40 region of the human LXRα promoter. A triple mutation in this H4-SBM abolished HNF-4α binding and reduced the activity of the promoter to 65% relative to the wild type. Furthermore, the mutant promoter could not be transactivated by HNF-4α. In conclusion, our data indicate that HNF-4α may have a wider role in cell and plasma cholesterol homeostasis by controlling the expression of LXRα in hepatic cells. PMID:26692490

  13. Structure and RNA recognition by the snRNA and snoRNA transport factor PHAX

    PubMed Central

    Mourão, André; Varrot, Annabelle; Mackereth, Cameron D.; Cusack, Stephen; Sattler, Michael

    2010-01-01

    Small nuclear and small nucleolar RNAs (snRNAs and snoRNAs) are critical components of snRNPs and snoRNPs and play an essential role in the maturation of, respectively, mRNAs and rRNAs within the nucleus of eukaryotic cells. Complex and specific pathways exist for the assembly of snRNPs and snoRNPs, involving, for instance, nucleocytoplasmic transport of snRNAs and intranuclear transport between compartments of snoRNAs. The phosphorylated adaptor for nuclear export (PHAX) is required for nuclear export of snRNAs in metazoans and also involved in the intranuclear transport of snoRNAs to Cajal bodies. PHAX contains a conserved single-stranded nucleic acid binding domain (RNA_GG_bind domain) with no sequence homology with any other known RNA-binding module. Here, we report NMR and X-ray crystallography studies that elucidate the structural basis for RNA recognition by the PHAX RNA-binding domain (PHAX-RBD). The crystal structure of the RNA_GG_bind domain from the parasite Cryptosporidium parvum (Cp RBD) forms well-folded dimers in solution in the absence of any ligand. The human PHAX-RBD is monomeric and only adopts a tertiary fold upon RNA binding. The PHAX-RBD represents a novel helical fold and binds single-stranded RNA with micromolar affinity without sequence specificity. RNA recognition by human PHAX-RBD is consistent with mutational analysis that affects RNA binding and PHAX-mediated nuclear export. Our data suggest that the PHAX-RBD mediates auxiliary RNA contacts with the snRNA and snoRNA substrates that are required for transport and/or substrate release. PMID:20430857

  14. The optimization of mechanical properties for nuclear transportation casks in ASTM A350 LF5

    SciTech Connect

    Price, S.; Honeyman, G.A.

    1997-12-31

    Transport flasks are required for the movement of spent nuclear fuel. Due to their nature of operation, it is necessary that these flasks are produced from forged steels with exceptional toughness properties. The material specification generally cited for flask manufacture is ASTM A350 Grade LF5 Class 1, a carbon-manganese-nickel alloy. The range of chemical analysis permitted by this specification is very broad and it is the responsibility of the material manufacturer to select a composition within this range which will satisfy all the mechanical properties requirements, and to ensure safe and reliable performance. Forgemasters Steel and Engineering Limited have experience in the manufacture of large high integrity fuel element flask forgings which extend over several decades. This experience and involvement in international standards in US, Europe and Japan has facilitated the development of an optimized analysis with a low carbon content, nickel levels towards the top end of the allowed range, a deliberate aluminum addition to control grain size and strictly controlled residual element levels. The resultant steel has excellent low temperature impact properties which greatly exceed the requirements of the specification. This analysis is now being adopted for the manufacture of all current transport flasks.

  15. Sulfate aerosol as a potential transport medium of radiocesium from the Fukushima nuclear accident.

    PubMed

    Kaneyasu, Naoki; Ohashi, Hideo; Suzuki, Fumie; Okuda, Tomoaki; Ikemori, Fumikazu

    2012-06-01

    To date, areas contaminated by radionuclides discharged from the Fukushima Dai-ichi nuclear power plant accident have been mapped in detail. However, size of the radionuclides and their mixing state with other aerosol components, which are critical in their removal from the atmosphere, have not yet been revealed. We measured activity size distributions of (134)Cs and (137)Cs in aerosols collected 47 days after the accident at Tsukuba, Japan, and found that the activity median aerodynamic diameters of (134)Cs and (137)Cs in the first sample (April 28-May 12) were 0.54 and 0.53 μm, respectively, and those in the second sample (May 12-26) were both 0.63 μm. The activity size distributions of these radiocesium were within the accumulation mode size range and almost overlapped with the mass size distribution of non-sea-salt sulfate aerosol. From the analysis of other aerosol components, we found that sulfate was the potential transport medium for these radionuclides, and resuspended soil particles that attached radionuclides were not the major airborne radioactive substances at the time of measurement. This explains the relatively similar activity sizes of radiocesium measured at various sites during the Chernobyl accident. Our results can serve as basic data for modeling the transport/deposition of radionuclides.

  16. Effects of molybdenum and silver on iodine transport in primary circuit on severe nuclear accidents

    SciTech Connect

    Kalilainen, J.; Rantanen, P.; Karkela, T.; Lipponen, M.; Auvinen, A.; Jokiniemi, J.

    2012-07-01

    This experimental study was a continuation of the study conducted at VTT to investigate the effects of reactions on primary circuit surfaces to transport of gaseous and aerosol phase iodine during the hypothetical severe nuclear accident. Cesium iodide was used as a precursor in every experiment. In the experiments it was observed that the hydrogen in the atmosphere decreased the fraction of released gaseous iodine. As the temperature was lowered, less iodine was released, but the fraction of gaseous iodine from the overall released iodine was increased. As molybdenum trioxide was introduced to the precursor, the fraction of gaseous iodine from the overall released iodine was increased significantly. Also, Mo decreased the transport of Cs and caused significant depositions to the reaction furnace. Addition of silver to the CsI precursor at 650 deg. C decreased the release of iodine as well as the fraction of gaseous iodine. At 400 deg. C, Ag + CsI as well as Ag + MoO{sub 3} + CsI precursor significantly increased the release of gaseous iodine, where almost no aerosol particles were released. With B{sub 2}O{sub 3} + CsI precursor it was observed that in the atmosphere without H{sub 2}O, the released iodine was mostly in gaseous form. (authors)

  17. Atypical ubiquitin ligase RNF31: the nuclear factor modulator in breast cancer progression.

    PubMed

    Zhu, Jian; Zhuang, Ting; Yang, Huijie; Li, Xin; Liu, Huandi; Wang, Hui

    2016-01-01

    Breast cancer causes the No.1 women cancer prevalence and the No.2 women cancer mortality worldwide. Nuclear receptor/transcriptional factor signaling is aberrant and plays important roles in breast cancer pathogenesis and evolution, such as estrogen receptor α (ERα/ESR1), tumor protein p53 (p53/TP53) and Nuclear factor kappa B (NFκB). About 60-70 % of breast tumors are ERα positive, while approximate 70 % of breast tumors are P53 wild type. Recent studies indicate that nuclear receptors/transcriptional factors could be tightly controlled through protein post-translational modification.The nuclear receptors/transcriptional factors could endure several types of modifications, including phosphorylation, acetylation and ubiquitination. Compared with the other two types of modifications, ubiquitination was mostly linked to protein degradation process, while few researches focused on the functional changes of the target proteins. Until recent years, ubiquitination process is no longer regarded as merely a protein degradation process, but aslo treated as one kind of modification signal.As an atypical E3 ubiquitin ligase, RNF31 was previously found to facilitate NFκB signaling transduction through linear ubiquitination on IKKγ(IκB kinase γ). Our previous studies showed important regulatory functions of RNF31 in controlling important oncogenic pathways in breast cancer, such as ERα and p53. This review highlights recent discoveries on RNF31 functions in nuclear factor modifications, breast cancer progression and possible therapeutic inhibitors targeting RNF31. PMID:27460922

  18. Binding of nuclear factors to functional domains of the duck hepatitis B virus enhancer.

    PubMed Central

    Lilienbaum, A; Crescenzo-Chaigne, B; Sall, A A; Pillot, J; Elfassi, E

    1993-01-01

    We have analyzed the structures, relative organization, and activities of binding sites for nuclear factors in the duck hepatitis B virus (duck HBV) enhancer. DNase I footprinting analysis and mobility shift assays demonstrate that this enhancer of 192 bp contains at least three binding sites for transcription factors: one for hepatocyte-adipocyte C/EBP, a second for the liver-specific transactivator hepatocyte nuclear factor 1 HNF-1, and a third for a factor, called F3, which binds to a DNA sequence bearing some resemblance to that for the ubiquitous factor EF-C. Analysis of transcriptional activity reveals that oligonucleotides corresponding to the individual binding sites, inserted upstream from a heterologous promoter, display very weak enhancer activity, whereas the enhancer encompassing these three sites displays very high activity. Analysis of duck HBV enhancer mutants indicates that the deletion of any of these sites leads to a modification of transcriptional enhancer activity. The hepatocyte nuclear factor 1 binding site is crucial, since an internal deletion of 14 bp abolishes the activity. The C/EBP site can act as repressor, and the F3 site is required for full activity. Comparative analysis reveals that the nuclear factors are similar to those bound to the human HBV enhancer but that the organization of their binding sites in the duck HBV enhancer is different. Images PMID:8371357

  19. Barometric gas transport along faults and its application to nuclear test-ban monitoring

    SciTech Connect

    Carrigan, C. R.; Heinle, R. A.; Hudson, G. B.; Nitao, J. J.; Zucca, J. J.

    1997-06-01

    Underground nuclear explosions produce a unique but evanescent set of radionuclide gases that potentially can be used in the context of an on-site, test-ban monitoring program to differentiate them from other detected events such as earthquakes or mining activity. In Part I of this report we describe an experiment to evaluate the upward transport of gases from an underground explosion using two gas tracers with very different diffusivities that were released in a 400- m-deep, chemical explosive detonation. The less diffusive (more massive) tracer was detected on a nearby geologic fault 50 days following the detonation while the more diffusive tracer was-- detected 375 days after release. Computer simulations indicate that the arrival time and the chromatographic behavior of transport are characteristic of barometrically induced flow in a fractured, porous matrix regime. For a hypothetical 1-kiloton fission explosion subject to the same weather and gas transport conditions of the chemical explosion, simulations predict the delectability of argon-37 after 80 days in spite of depletion by radioactive decay. Largely because of the earlier arrival of xenon-133, owing to its lower binary gas diffusivity, the exceedingly short lived isotope should also be detectable-arriving about 30 days earlier than argon. in Part II we consider that our prediction of the delectability of argon and xenon is based upon the small volume (0.00001 M3) sampling technique of the NPE tracer-gas sampling study while actual sampling for radionuclides would involve drawing much larger volume (possibly 0.1- 1 M3) gas samples from the near-surface.

  20. Reassessment of selected factors affecting siting of Nuclear Power Plants

    SciTech Connect

    Davis, R.E.; Hanson, A.L.; Mubayi, V.; Nourbakhsh, H.P.

    1997-02-01

    Brookhaven National Laboratory has performed a series of probabilistic consequence assessment calculations for nuclear reactor siting. This study takes into account recent insights into severe accident source terms and examines consequences in a risk based format consistent with the quantitative health objectives (QHOs) of the NRC`s Safety Goal Policy. Simplified severe accident source terms developed in this study are based on the risk insights of NUREG-1150. The results of the study indicate that both the quantity of radioactivity released in a severe accident as well as the likelihood of a release are lower than those predicted in earlier studies. The accident risks using the simplified source terms are examined at a series of generic plant sites, that vary in population distribution, meteorological conditions, and exclusion area boundary distances. Sensitivity calculations are performed to evaluate the effects of emergency protective action assumptions on the risk of prompt fatality and latent cancers fatality, and population relocation. The study finds that based on the new source terms the prompt and latent fatality risks at all generic sites meet the QHOs of the NRC`s Safety Goal Policy by margins ranging from one to more than three orders of magnitude. 4 refs., 17 figs., 24 tabs.

  1. Towards high precision measurements of nuclear g-factors for the Be isotopes

    NASA Astrophysics Data System (ADS)

    Takamine, A.; Wada, M.; Okada, K.; Ito, Y.; Schury, P.; Arai, F.; Katayama, I.; Imamura, K.; Ichikawa, Y.; Ueno, H.; Wollnik, H.; Schuessler, H. A.

    2016-06-01

    We describe the present status of future high-precision measurements of nuclear g-factors utilizing laser-microwave double and laser-microwave-rf triple resonance methods for online-trapped, laser-cooled radioactive beryllium isotope ions. These methods have applicability to other suitably chosen isotopes and for beryllium show promise in deducing the hyperfine anomaly of 11Be with a sufficiently high precision to study the nuclear magnetization distribution of this one-neutron halo nucleus in a nuclear-model-independent manner.

  2. GCR Transport in the Brain: Assessment of Self-Shielding, Columnar Damage, and Nuclear Reactions on Cell Inactivation Rates

    NASA Technical Reports Server (NTRS)

    Shavers, M. R.; Atwell, W.; Cucinotta, F. A.; Badhwar, G. D. (Technical Monitor)

    1999-01-01

    Radiation shield design is driven by the need to limit radiation risks while optimizing risk reduction with launch mass/expense penalties. Both limitation and optimization objectives require the development of accurate and complete means for evaluating the effectiveness of various shield materials and body-self shielding. For galactic cosmic rays (GCR), biophysical response models indicate that track structure effects lead to substantially different assessments of shielding effectiveness relative to assessments based on LET-dependent quality factors. Methods for assessing risk to the central nervous system (CNS) from heavy ions are poorly understood at this time. High-energy and charge (HZE) ion can produce tissue events resulting in damage to clusters of cells in a columnar fashion, especially for stopping heavy ions. Grahn (1973) and Todd (1986) have discussed a microlesion concept or model of stochastic tissue events in analyzing damage from HZE's. Some tissues, including the CNS, maybe sensitive to microlesion's or stochastic tissue events in a manner not illuminated by either conventional dosimetry or fluence-based risk factors. HZE ions may also produce important lateral damage to adjacent cells. Fluences of high-energy proton and alpha particles in the GCR are many times higher than HZE ions. Behind spacecraft and body self-shielding the ratio of protons, alpha particles, and neutrons to HZE ions increases several-fold from free-space values. Models of GCR damage behind shielding have placed large concern on the role of target fragments produced from tissue atoms. The self-shielding of the brain reduces the number of heavy ions reaching the interior regions by a large amount and the remaining light particle environment (protons, neutrons, deuterons. and alpha particles) may be the greatest concern. Tracks of high-energy proton produce nuclear reactions in tissue, which can deposit doses of more than 1 Gv within 5 - 10 cell layers. Information on rates of

  3. Crm1-mediated nuclear export of the Schizosaccharomyces pombe transcription factor Cuf1 during a shift from low to high copper concentrations.

    PubMed

    Beaudoin, Jude; Labbé, Simon

    2007-05-01

    In this study, we examine the fate of the nuclear pool of the Schizosaccharomyces pombe transcription factor Cuf1 in response to variations in copper levels. A nuclear pool of Cuf1-green fluorescent protein (GFP) was generated by expressing a functional cuf1(+)-GFP allele in the presence of a copper chelator. We then extinguished cuf1(+)-GFP expression and tracked the changes in the localization of the nuclear pool of Cuf1-GFP in the presence of low or high copper concentrations. Treating cells with copper as well as silver ions resulted in the nuclear export of Cuf1. We identified a leucine-rich nuclear export signal (NES), (349)LAALNHISAL(358), within the C-terminal region of Cuf1. Mutations in this sequence abrogated Cuf1 export from the nucleus. Furthermore, amino acid substitutions that impair Cuf1 NES function resulted in increased target gene expression and a concomitant cellular hypersensitivity to copper. Export of the wild-type Cuf1 protein was inhibited by leptomycin B (LMB), a specific inhibitor of the nuclear export protein Crm1. We further show that cells expressing a temperature-sensitive mutation in crm1(+) exhibit increased nuclear accumulation of Cuf1 at the nonpermissive temperature. Although wild-type Cuf1 is localized in the nucleus in both conditions, we observed that the protein can still be inactivated by copper, resulting in the repression of ctr4(+) gene expression in the presence of exogenous copper. These results demonstrate that nuclear accumulation of Cuf1 per se is not sufficient to cause the unregulated expression of the copper transport genes like ctr4(+). In addition to nuclear localization, a functional Cys-rich domain or NES element in Cuf1 is required to appropriately regulate copper transport gene expression in response to changes in intracellular copper concentration.

  4. A novel role for nuclear factor-erythroid 2 in erythroid maturation by modulation of mitochondrial autophagy.

    PubMed

    Gothwal, Monika; Wehrle, Julius; Aumann, Konrad; Zimmermann, Vanessa; Gründer, Albert; Pahl, Heike L

    2016-09-01

    We have recently demonstrated that the transcription factor nuclear factor-erythroid 2, which is critical for erythroid maturation and globin gene expression, plays an important role in the pathophysiology of myeloproliferative neoplasms. Myeloproliferative neoplasm patients display elevated levels of nuclear factor-erythroid 2 and transgenic mice overexpressing the transcription factor develop myeloproliferative neoplasm, albeit, surprisingly without erythrocytosis. Nuclear factor-erythroid 2 transgenic mice show both a reticulocytosis and a concomitant increase in iron deposits in the spleen, suggesting both enhanced erythrocyte production and increased red blood cell destruction. We therefore hypothesized that elevated nuclear factor-erythroid 2 levels may lead to increased erythrocyte destruction by interfering with organelle clearance during erythroid maturation. We have previously shown that nuclear factor-erythroid 2 overexpression delays erythroid maturation of human hematopoietic stem cells. Here we report that increased nuclear factor-erythroid 2 levels also impede murine maturation by retarding mitochondrial depolarization and delaying mitochondrial elimination. In addition, ribosome autophagy is delayed in transgenics. We demonstrate that the autophagy genes NIX and ULK1 are direct novel nuclear factor-erythroid 2 target genes, as these loci are bound by nuclear factor-erythroid 2 in chromatin immunoprecipitation assays. Moreover, Nix and Ulk1 expression is increased in transgenic mice and in granulocytes from polycythemia vera patients. This is the first report implying a role for nuclear factor-erythroid 2 in erythroid maturation by affecting autophagy. PMID:27479815

  5. A novel role for nuclear factor-erythroid 2 in erythroid maturation by modulation of mitochondrial autophagy.

    PubMed

    Gothwal, Monika; Wehrle, Julius; Aumann, Konrad; Zimmermann, Vanessa; Gründer, Albert; Pahl, Heike L

    2016-09-01

    We have recently demonstrated that the transcription factor nuclear factor-erythroid 2, which is critical for erythroid maturation and globin gene expression, plays an important role in the pathophysiology of myeloproliferative neoplasms. Myeloproliferative neoplasm patients display elevated levels of nuclear factor-erythroid 2 and transgenic mice overexpressing the transcription factor develop myeloproliferative neoplasm, albeit, surprisingly without erythrocytosis. Nuclear factor-erythroid 2 transgenic mice show both a reticulocytosis and a concomitant increase in iron deposits in the spleen, suggesting both enhanced erythrocyte production and increased red blood cell destruction. We therefore hypothesized that elevated nuclear factor-erythroid 2 levels may lead to increased erythrocyte destruction by interfering with organelle clearance during erythroid maturation. We have previously shown that nuclear factor-erythroid 2 overexpression delays erythroid maturation of human hematopoietic stem cells. Here we report that increased nuclear factor-erythroid 2 levels also impede murine maturation by retarding mitochondrial depolarization and delaying mitochondrial elimination. In addition, ribosome autophagy is delayed in transgenics. We demonstrate that the autophagy genes NIX and ULK1 are direct novel nuclear factor-erythroid 2 target genes, as these loci are bound by nuclear factor-erythroid 2 in chromatin immunoprecipitation assays. Moreover, Nix and Ulk1 expression is increased in transgenic mice and in granulocytes from polycythemia vera patients. This is the first report implying a role for nuclear factor-erythroid 2 in erythroid maturation by affecting autophagy.

  6. A novel role for nuclear factor-erythroid 2 in erythroid maturation by modulation of mitochondrial autophagy

    PubMed Central

    Gothwal, Monika; Wehrle, Julius; Aumann, Konrad; Zimmermann, Vanessa; Gründer, Albert; Pahl, Heike L.

    2016-01-01

    We have recently demonstrated that the transcription factor nuclear factor-erythroid 2, which is critical for erythroid maturation and globin gene expression, plays an important role in the pathophysiology of myeloproliferative neoplasms. Myeloproliferative neoplasm patients display elevated levels of nuclear factor-erythroid 2 and transgenic mice overexpressing the transcription factor develop myeloproliferative neoplasm, albeit, surprisingly without erythrocytosis. Nuclear factor-erythroid 2 transgenic mice show both a reticulocytosis and a concomitant increase in iron deposits in the spleen, suggesting both enhanced erythrocyte production and increased red blood cell destruction. We therefore hypothesized that elevated nuclear factor-erythroid 2 levels may lead to increased erythrocyte destruction by interfering with organelle clearance during erythroid maturation. We have previously shown that nuclear factor-erythroid 2 overexpression delays erythroid maturation of human hematopoietic stem cells. Here we report that increased nuclear factor-erythroid 2 levels also impede murine maturation by retarding mitochondrial depolarization and delaying mitochondrial elimination. In addition, ribosome autophagy is delayed in transgenics. We demonstrate that the autophagy genes NIX and ULK1 are direct novel nuclear factor-erythroid 2 target genes, as these loci are bound by nuclear factor-erythroid 2 in chromatin immunoprecipitation assays. Moreover, Nix and Ulk1 expression is increased in transgenic mice and in granulocytes from polycythemia vera patients. This is the first report implying a role for nuclear factor-erythroid 2 in erythroid maturation by affecting autophagy. PMID:27479815

  7. Source term estimation of radioxenon released from the Fukushima Dai-ichi nuclear reactors using measured air concentrations and atmospheric transport modeling.

    PubMed

    Eslinger, P W; Biegalski, S R; Bowyer, T W; Cooper, M W; Haas, D A; Hayes, J C; Hoffman, I; Korpach, E; Yi, J; Miley, H S; Rishel, J P; Ungar, K; White, B; Woods, V T

    2014-01-01

    Systems designed to monitor airborne radionuclides released from underground nuclear explosions detected radioactive fallout across the northern hemisphere resulting from the Fukushima Dai-ichi Nuclear Power Plant accident in March 2011. Sampling data from multiple International Modeling System locations are combined with atmospheric transport modeling to estimate the magnitude and time sequence of releases of (133)Xe. Modeled dilution factors at five different detection locations were combined with 57 atmospheric concentration measurements of (133)Xe taken from March 18 to March 23 to estimate the source term. This analysis suggests that 92% of the 1.24 × 10(19) Bq of (133)Xe present in the three operating reactors at the time of the earthquake was released to the atmosphere over a 3 d period. An uncertainty analysis bounds the release estimates to 54-129% of available (133)Xe inventory.

  8. Nuclear translocation of nuclear factor of activated T cells (NFAT) as a quantitative pharmacodynamic parameter for tacrolimus.

    PubMed

    Maguire, Orla; Tornatore, Kathleen M; O'Loughlin, Kieran L; Venuto, Rocco C; Minderman, Hans

    2013-12-01

    Nuclear factor of activated T cells (NFAT) is a family of transcription factors involved in regulating the immune response. The canonical NFAT pathway is calcium-dependent and upon activation, NFAT is dephosphorylated by the phosphatase, calcineurin. This results in its translocation from the cytoplasm to the nucleus and transcription of downstream target genes that include the cytokines IL-2, IL-10, and IFNγ. Calcineurin inhibitors including tacrolimus inhibit the NFAT pathway and are used as immunosuppressants in transplant settings to prevent graft rejection. There is, as yet, no direct means to monitor tacrolimus pharmacodynamics. In this study, a rapid, quantitative, image cytometry-based measurement of nuclear translocation of NFAT1 is used to evaluate NFAT activation in T cells and its tacrolimus-induced inhibition. A strong dose-dependent correlation between NFAT1 inhibition and tacrolimus dose is demonstrated in vitro. Time kinetic analysis of NFAT1 inhibition in plasma from stable renal transplant recipients before and after an in vivo dose with tacrolimus correlated with the expected pharmacokinetic profile of tacrolimus. This was further corroborated by analysis of patients' autologous CD4 and CD8 T cells. This is the first report to show that the measurement of NFAT1 activation potential by nuclear translocation can be used as a direct, sensitive, reproducible and quantitative pharmacodynamic readout for tacrolimus action. These results, and the rapid turnaround time for this assay, warrant its evaluation in a larger clinical setting to assess its role in therapeutic drug monitoring of calcineurin inhibitors.

  9. Modeling most likely pathways for smuggling radioactive and special nuclear materials on a worldwide multi-modal transportation network

    SciTech Connect

    Saeger, Kevin J; Cuellar, Leticia

    2010-10-28

    Nuclear weapons proliferation is an existing and growing worldwide problem. To help with devising strategies and supporting decisions to interdict the transport of nuclear material, we developed the Pathway Analysis, Threat Response and Interdiction Options Tool (PATRIOT) that provides an analytical approach for evaluating the probability that an adversary smuggling radioactive or special nuclear material will be detected during transit. We incorporate a global, multi-modal transportation network, explicit representation of designed and serendipitous detection opportunities, and multiple threat devices, material types, and shielding levels. This paper presents the general structure of PATRIOT, all focuses on the theoretical framework used to model the reliabilities of all network components that are used to predict the most likely pathways to the target.

  10. Modeling most likely pathways for smuggling radioactive and special nuclear materials on a worldwide multimodal transportation network

    SciTech Connect

    Saeger, Kevin J; Cuellar, Leticia

    2010-01-01

    Nuclear weapons proliferation is an existing and growing worldwide problem. To help with devising strategies and supporting decisions to interdict the transport of nuclear material, we developed the Pathway Analysis, Threat Response and Interdiction Options Tool (PATRIOT) that provides an analytical approach for evaluating the probability that an adversary smuggling radioactive or special nuclear material will be detected during transit. We incorporate a global, multi-modal transportation network, explicit representation of designed and serendipitous detection opportunities, and multiple threat devices, material types, and shielding levels. This paper presents the general structure of PATRIOT, and focuses on the theoretical framework used to model the reliabilities of all network components that are used to predict the most likely pathways to the target.

  11. Identification, Ki determination and CoMFA analysis of nuclear receptor ligands as competitive inhibitors of OATP1B1-mediated estradiol-17β-glucuronide transport

    PubMed Central

    Gui, Chunshan; Wahlgren, Brett; Lushington, Gerald H.; Hagenbuch, Bruno

    2009-01-01

    Evidence shows that drug-drug interactions can occur at the level of drug transporters such as the organic anion transporting polypeptides (OATPs), a group of membrane solute carriers that mediate the sodium-independent transport of a wide range of amphipathic organic compounds. The polyspecific OATP1B1 is exclusively expressed at the basolateral membrane of hepatocytes and mediates uptake of amphipathic organic compounds from blood into hepatocytes. Nuclear receptors are ligand-activated transcription factors that play an important role in xenobiotic disposition and human diseases. Quite a few nuclear receptor ligands interact with transport proteins. A high-resolution three-dimensional structure is critical to understand the polyspecificity of OATP1B1 to predict and prevent adverse drug-drug interactions. Unfortunately there are no crystal structures of OATPs/Oatps available to date. Therefore, in this study we attempted to elucidate the characteristics of the substrate binding site of OATP1B1 based on small molecules interacting with it. First, we identified inhibitors of the OATP1B1 model substrate estradiol-17β-glucuronide from about forty nuclear receptor ligands. Among them, GW1929, paclitaxel and troglitazone were strong inhibitors, while 5α-androstane, 5α-androstane-3β, 17β-diol-17-hexahydrobenzoate and estradiol-3-benzoate were weak inhibitors. Then, we selected 25 compounds and performed inhibition kinetic studies to identify competitive inhibitors and determine their Ki values which ranged from submicromolar to submillimolar. Finally, we performed CoMFA analysis on the identified competitive inhibitors. The CoMFA results indicate that the substrate binding site of OATP1B1 consists of a large hydrophobic middle part with basic residues at both ends that could be very important for substrate binding. PMID:19427586

  12. Requirement of nucleotide exchange factor for Ypt1 GTPase mediated protein transport.

    PubMed

    Jones, S; Litt, R J; Richardson, C J; Segev, N

    1995-09-01

    Small GTPases of the rab family are involved in the regulation of vesicular transport. It is believed that cycling between the GTP- and GDP-bound forms, and accessory factors regulating this cycling are crucial for rab function. However, an essential role for rab nucleotide exchange factors has not yet been demonstrated. In this report we show the requirement of nucleotide exchange factor activity for Ypt1 GTPase mediated protein transport. The Ypt1 protein, a member of the rab family, plays a role in targeting vesicles to the acceptor compartment and is essential for the first two steps of the yeast secretory pathway. We use two YPT1 dominant mutations that contain alterations in a highly conserved GTP-binding domain, N121I and D124N. YPT1-D124N is a novel mutation that encodes a protein with nucleotide specificity modified from guanine to xanthine. This provides a tool for the study of an individual rab GTPase in crude extracts: a xanthosine triphosphate (XTP)-dependent conditional dominant mutation. Both mutations confer growth inhibition and a block in protein secretion when expressed in vivo. The purified mutant proteins do not bind either GDP or GTP. Moreover, they completely inhibit the ability of the exchange factor to stimulate nucleotide exchange for wild type Ypt1 protein, and are potent inhibitors of ER to Golgi transport in vitro at the vesicle targeting step. The inhibitory effects of the Ypt1-D124N mutant protein on both nucleotide exchange activity and protein transport in vitro can be relieved by XTP, indicating that it is the nucleotide-free form of the mutant protein that is inhibitory. These results suggest that the dominant mutant proteins inhibit protein transport by sequestering the exchange factor from the wild type Ypt1 protein, and that this factor has an essential role in vesicular transport.

  13. Characterization of a multiple endogenously expressed adenosine triphosphate-binding cassette transporters using nuclear and cellular membrane affinity chromatography columns.

    PubMed

    Habicht, K-L; Singh, N S; Khadeer, M A; Shimmo, R; Wainer, I W; Moaddel, R

    2014-04-25

    Glioblastoma multiforme is an aggressive form of human astrocytoma, with poor prognosis due to multi-drug resistance to a number of anticancer drugs. The observed multi-drug resistance is primarily due to the efflux activity of ATP-Binding Cassette (ABC) efflux transporters such as Pgp, MRP1 and BCRP. The expression of these transporters has been demonstrated in nuclear and cellular membranes of the LN-229 human glioblastoma cell line. Nuclear membrane and cellular membrane fragments from LN-229 cells were immobilized on the IAM stationary phase to create nuclear and cellular membrane affinity chromatography columns, (NMAC(LN-229)) and (CMAC(LN-229)), respectively. Pgp, MRP1 and BCRP transporters co-immobilized on both columns were characterized and compared by establishing the binding affinities for estrone-3-sulfate (3.8 vs. 3.7μM), verapamil (0.6 vs. 0.7μM) and prazosin (0.099 vs. 0.033μM) on each column and no significant differences were observed. Since the marker ligands had overlapping selectivities, the selective characterization of each transporter was carried out by saturation of the binding sites of the non-targeted transporters. The addition of verapamil (Pgp and MRP1 substrate) to the mobile phase allowed the comparative screening of eight compounds at the nuclear and cellular BCRP using etoposide as the marker ligand. AZT increased the retention of etoposide (+15%), a positive allosteric interaction, on the CMAC(LN-229) column and decreased it (-5%) on the NMAC(LN-229), while the opposite effect was produced by rhodamine. The results indicate that there are differences between the cellular and nuclear membrane expressed BCRP and that NMAC and CMAC columns can be used to probe these differences.

  14. Characterization of a multiple endogenously expressed Adenosine triphosphate-Binding Cassette transporters using nuclear and cellular membrane affinity chromatography columns

    PubMed Central

    Khadeer, M.A.; Shimmo, R.; Wainer, I.W.; Moaddel, R.

    2014-01-01

    Glioblastoma multiforme is an aggressive form of human astrocytoma, with poor prognosis due to multi-drug resistance to a number of anticancer drugs. The observed multi-drug resistance is primarily due to the efflux activity of ATP Binding Cassette (ABC) efflux transporters such as Pgp, MRP1 and BCRP. The expression of these transporters has been demonstrated in nuclear and cellular membranes of the LN-229 human glioblastoma cell line. Nuclear membrane and cellular membrane fragments from LN229 cells were immobilized on the IAM stationary phase to create nuclear and cellular membrane affinity chromatography columns, (NMAC(LN229)) and (CMAC(LN229)), respectively. Pgp, MRP1and BCRP transporters co-immobilized on both columns was characterized and compared by establishing the binding affinities for estrone-3-sulfate (3.8 vs 3.7μM), verapamil (0.6 vs 0.7μM) and prazosin (0.099 vs 0.033μM) on each column and no significant differences were observed. Since the marker ligands had overlapping selectivities, the selective characterization of each transporter was carried out by saturation of the binding sites of the non-targeted transporters. The addition of verapamil (Pgp and MRP1 substrate) to the mobile phase allowed the comparative screening of 8 compounds at the nuclear and cellular BCRP using etoposide as the marker ligand. AZT increased the retention of etoposide (+15%), a positive allosteric interaction, on the CMAC(LN229) column and decreased it (−5%) on the NMAC(LN229), while the opposite effect was produced by rhodamine. The results indicate that there are differences between the cellular and nuclear membrane expressed BCRP and that NMAC and CMAC columns can be used to probe these differences. PMID:24642394

  15. Structural insight in the toppling mechanism of an energy-coupling factor transporter

    PubMed Central

    Swier, Lotteke J. Y. M.; Guskov, Albert; Slotboom, Dirk J.

    2016-01-01

    Energy-coupling factor (ECF) transporters mediate uptake of micronutrients in prokaryotes. The transporters consist of an S-component that binds the transported substrate and an ECF module (EcfAA′T) that binds and hydrolyses ATP. The mechanism of transport is poorly understood but presumably involves an unusual step in which the membrane-embedded S-component topples over to carry the substrate across the membrane. In many ECF transporters, the S-component dissociates from the ECF module after transport. Subsequently, substrate-bound S-components out-compete the empty proteins for re-binding to the ECF module in a new round of transport. Here we present crystal structures of the folate-specific transporter ECF–FolT from Lactobacillus delbrueckii. Interaction of the ECF module with FolT stabilizes the toppled state, and simultaneously destroys the high-affinity folate-binding site, allowing substrate release into the cytosol. We hypothesize that differences in the kinetics of toppling can explain how substrate-loaded FolT out-competes apo-FolT for association with the ECF module. PMID:27026363

  16. The unit cost factors and calculation methods for decommissioning - Cost estimation of nuclear research facilities

    SciTech Connect

    Kwan-Seong Jeong; Dong-Gyu Lee; Chong-Hun Jung; Kune-Woo Lee

    2007-07-01

    Available in abstract form only. Full text of publication follows: The uncertainties of decommissioning costs increase high due to several conditions. Decommissioning cost estimation depends on the complexity of nuclear installations, its site-specific physical and radiological inventories. Therefore, the decommissioning costs of nuclear research facilities must be estimated in accordance with the detailed sub-tasks and resources by the tasks of decommissioning activities. By selecting the classified activities and resources, costs are calculated by the items and then the total costs of all decommissioning activities are reshuffled to match with its usage and objectives. And the decommissioning cost of nuclear research facilities is calculated by applying a unit cost factor method on which classification of decommissioning works fitted with the features and specifications of decommissioning objects and establishment of composition factors are based. Decommissioning costs of nuclear research facilities are composed of labor cost, equipment and materials cost. Of these three categorical costs, the calculation of labor costs are very important because decommissioning activities mainly depend on labor force. Labor costs in decommissioning activities are calculated on the basis of working time consumed in decommissioning objects and works. The working times are figured out of unit cost factors and work difficulty factors. Finally, labor costs are figured out by using these factors as parameters of calculation. The accuracy of decommissioning cost estimation results is much higher compared to the real decommissioning works. (authors)

  17. NRC Technical Research Program to Evaluate Extended Storage and Transportation of Spent Nuclear Fuel - 12547

    SciTech Connect

    Einziger, R.E.; Compton, K.; Gordon, M.; Ahn, T.; Gonzales, H.; Pan, Y.

    2012-07-01

    Any new direction proposed for the back-end of spent nuclear fuel (SNF) cycle will require storage of SNF beyond the current licensing periods. The Nuclear Regulatory Commission (NRC) has established a technical research program to determine if any changes in the 10 CFR part 71, and 72 requirements, and associated guidance might be necessary to regulate the safety of anticipated extended storage, and subsequent transport of SNF. This three part program of: 1) analysis of knowledge gaps in the potential degradation of materials, 2) short-term research and modeling, and 3) long-term demonstration of systems, will allow the NRC to make informed regulatory changes, and determine when and if additional monitoring and inspection of the systems is necessary. The NRC has started a research program to obtain data necessary to determine if the current regulatory guidance is sufficient if interim dry storage has to be extended beyond the currently approved licensing periods. The three-phased approach consists of: - the identification and prioritization of potential degradation of the components related to the safe operation of a dry cask storage system, - short-term research to determine if the initial analysis was correct, and - a long-term prototypic demonstration project to confirm the models and results obtained in the short-term research. The gap analysis has identified issues with the SCC of the stainless steel canisters, and SNF behavior. Issues impacting the SNF and canister internal performance such as high and low temperature distributions, and drying have also been identified. Research to evaluate these issues is underway. Evaluations have been conducted to determine the relative values that various types of long-term demonstration projects might provide. These projects or follow-on work is expected to continue over the next five years. (authors)

  18. Binding site requirements and differential representation of TGF factors in nuclear ASF-1 activity.

    PubMed

    Lam, E; Lam, Y K

    1995-09-25

    Activating sequence factor 1 (ASF-1) is a nuclear DNA-binding activity that is found in monocots and dicots. It interacts with several TGACG-containing elements that have been characterized from viral and T-DNA genes, the prototypes of which are the as-1 element of the CaMV 35S promoter and the ocs element from the octopine synthase promoter. This class of cis-acting elements can respond to auxin and salicylic acid treatments. Consistent with these observations, we have shown that ASF-1 can interact with promoter elements of an auxin-inducible tobacco gene GNT35, encoding a glutathione S-transferase. Characterization of the nuclear factors that make up ASF-1 activity in vivo will be an important step toward understanding this induction phenomenon. The TGA family of basic-leucine-zipper (bZIP) proteins are good candidates for the ASF-1 nuclear factor. However, there may be as many as seven distinct TGA genes in Arabidopsis, five of which have now been reported. In this study, we expressed the cDNAs that encode four of these five Arabidopsis TGA factors in vitro and compared their DNA-binding behavior using two types of TGACG-containing elements. With specific antisera prepared against three of the five known Arabidopsis TGA factors, we also investigated the relative abundance of these three proteins within the ASF-1 activities of root and leaf nuclear extracts. Our results indicate that these TGA factors bind to DNA with different degrees of cooperativity and their relative affinity toward as-1 also can differ significantly. The results of a supershift assay suggested that only one of the three TGA factors represented a significant component of nuclear ASF-1 activity. Arabidopsis TGA2 comprises approximately 33 and 50% of the ASF-1 activity detected in root and leaf nuclear extracts respectively. These results suggest that each member of the TGA factor family may be differentially regulated and that they may play different roles by virtue of their distinct DNA

  19. Nuclear translocation of fibroblast growth factor-2 (FGF2) is regulated by Karyopherin-β2 and Ran GTPase in human glioblastoma cells.

    PubMed

    Wang, Feng; Yang, Lijun; Shi, Lin; Li, Qian; Zhang, Gengshen; Wu, Jianliang; Zheng, Jun; Jiao, Baohua

    2015-08-28

    Human glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system (CNS). Fibroblast growth factor-2 (FGF2) belongs to the FGF superfamily and functions as a potential oncoprotein in GBM. FGF2 has low molecular weight (18K) and high molecular weight (HMW) isoforms. Nuclear accumulation of HMW-FGF2 strongly promotes glioblastoma cell proliferation, yet mechanism governing such cellular distribution remains unexplored. We investigated the mechanisms regulating FGF2 cellular localization in T98G human brain glioblastoma cells. We found HMW-FGF2, but not 18K-FGF2, is primarily located in the nucleus and interacts with nuclear transport protein Karyopherin-β2/Transportin (Kapβ2). SiRNA-directed Kapβ2 knockdown significantly reduced HMW-FGF2's nuclear translocation. Moreover, inhibiting Ran GTPase activity also resulted in decreased HMW-FGF2 nuclear accumulation. Proliferation of T98G cells is greatly enhanced with transfections HMW-FGF2. Decreased PTEN expression and activated Akt signaling were observed upon HMW-FGF2 overexpression and might mediate pro-survival effect of FGF2. Interestingly, addition of nuclear localization signal (NLS) to 18K-FGF2 forced its nuclear import and dramatically increased cell proliferation and Akt activation. These findings demonstrated for the first time the molecular mechanisms for FGF2's nuclear import, which promotes GBM cell proliferation and survival, providing novel insights to the development of GBM treatments. PMID:26056081

  20. Nuclear translocation of fibroblast growth factor-2 (FGF2) is regulated by Karyopherin-β2 and Ran GTPase in human glioblastoma cells.

    PubMed

    Wang, Feng; Yang, Lijun; Shi, Lin; Li, Qian; Zhang, Gengshen; Wu, Jianliang; Zheng, Jun; Jiao, Baohua

    2015-08-28

    Human glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system (CNS). Fibroblast growth factor-2 (FGF2) belongs to the FGF superfamily and functions as a potential oncoprotein in GBM. FGF2 has low molecular weight (18K) and high molecular weight (HMW) isoforms. Nuclear accumulation of HMW-FGF2 strongly promotes glioblastoma cell proliferation, yet mechanism governing such cellular distribution remains unexplored. We investigated the mechanisms regulating FGF2 cellular localization in T98G human brain glioblastoma cells. We found HMW-FGF2, but not 18K-FGF2, is primarily located in the nucleus and interacts with nuclear transport protein Karyopherin-β2/Transportin (Kapβ2). SiRNA-directed Kapβ2 knockdown significantly reduced HMW-FGF2's nuclear translocation. Moreover, inhibiting Ran GTPase activity also resulted in decreased HMW-FGF2 nuclear accumulation. Proliferation of T98G cells is greatly enhanced with transfections HMW-FGF2. Decreased PTEN expression and activated Akt signaling were observed upon HMW-FGF2 overexpression and might mediate pro-survival effect of FGF2. Interestingly, addition of nuclear localization signal (NLS) to 18K-FGF2 forced its nuclear import and dramatically increased cell proliferation and Akt activation. These findings demonstrated for the first time the molecular mechanisms for FGF2's nuclear import, which promotes GBM cell proliferation and survival, providing novel insights to the development of GBM treatments.

  1. Neutron Transport Characteristics of a Nuclear Reactor Based Dynamic Neutron Imaging System

    SciTech Connect

    Khaial, Anas M.; Harvel, Glenn D.; Chang, Jen-Shih

    2006-07-01

    An advanced dynamic neutron imaging system has been constructed in the McMaster Nuclear Reactor (MNR) for nondestructive testing and multi-phase flow studies in energy and environmental applications. A high quality neutron beam is required with a thermal neutron flux greater than 5.0 x 10{sup 6} n/cm{sup 2}-s and a collimation ratio of 120 at image plane to promote high-speed neutron imaging up to 2000 frames per second. Neutron source strength and neutron transport have been experimentally and numerically investigated. Neutron source strength at the beam tube entrance was evaluated experimentally by measuring the thermal and fast neutron fluxes, and simple analytical neutron transport calculations were performed based upon these measured neutron fluxes to predict facility components in accordance with high-speed dynamic neutron imaging and operation safety requirements. Monte-Carlo simulations (using MCNP-4B code) with multiple neutron energy groups have also been used to validate neutron beam parameters and to ensure shielding capabilities of facility shutter and cave walls. Neutron flux distributions at the image plane and the neutron beam characteristics were experimentally measured by irradiating a two-dimensional array of Copper foils and using a real-time neutron radiography system. The neutron image characteristics -- such as neutron flux, image size, beam quality -- measured experimentally and predicted numerically for beam tube, beam shutter and radiography cave are compared and discussed in detail in this paper. The experimental results show that thermal neutron flux at image plane is nearly uniform over an imaging area of 20.0-cm diameter and its magnitude ranges from 8.0 x 10{sup 6} - 1.0 x 10{sup 7} n/cm{sup 2}-sec while the neutron-to-gamma ratio is 6.0 x 10{sup 5} n/cm{sup 2}-{mu}Sv. (authors)

  2. Factors influencing the transport of actinides in the groundwater environment. Final report

    SciTech Connect

    Sheppard, J.C.; Kittrick, J.A.

    1983-07-31

    This report summarizes investigations of factors that significantly influence the transport of actinide cations in the groundwater environment. Briefly, measurements of diffusion coefficients for Am(III), Cm(III), and Np(V) in moist US soils indicated that diffusion is negligible compared to mass transport in flowing groundwater. Diffusion coefficients do, however, indicate that, in the absence of flowing water, actinide elements will migrate only a few centimeters in a thousand years. The remaining investigations were devoted to the determination of distribution ratios (K/sub d/s) for representative US soils, factors influencing them, and chemical and physical processes related to transport of actinides in groundwaters. The computer code GARD was modified to include complex formation to test the importance of humic acid complexing on the rate of transport of actinides in groundwaters. Use of the formation constant and a range of humic acid, even at rather low concentrations of 10/sup -5/ to 10/sup -6/ molar, significantly increases the actinide transport rate in a flowing aquifer. These computer calculations show that any strong complexing agent will have a similar effect on actinide transport in the groundwater environment. 32 references, 9 figures.

  3. Bohmian mechanics in the exact factorization of electron-nuclear wave functions

    NASA Astrophysics Data System (ADS)

    Suzuki, Yasumitsu; Watanabe, Kazuyuki

    2016-09-01

    The exact factorization of an electron-nuclear wave function [A. Abedi, N. T. Maitra, and E. K. U. Gross, Phys. Rev. Lett. 105, 123002 (2010), 10.1103/PhysRevLett.105.123002] allows us to define the rigorous nuclear time-dependent Schrödinger equation (TDSE) with a time-dependent potential-energy surface (TDPES) that fully accounts for the coupling to the electronic motion and drives the nuclear wave-packet dynamics. Here, we study whether the propagation of multiple classical trajectories can reproduce the quantum nuclear motion in strong-field processes when their motions are governed by the quantum Hamilton-Jacobi equation derived by applying Bohmian mechanics to this exact nuclear TDSE. We demonstrate that multiple classical trajectories propagated by the force from the gradient of the exact TDPES plus the Bohmian quantum potential can reproduce the strong-field dissociation dynamics of a one-dimensional model of the H2 + molecule. Our results show that the force from the Bohmian quantum potential plays a non-negligible role in yielding quantum nuclear dynamics in the strong-field process studied here, where ionization and/or splitting of nuclear probability density occurs.

  4. Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1)

    PubMed Central

    Terranova, Christopher; Narla, Sridhar T.; Lee, Yu-Wei; Bard, Jonathan; Parikh, Abhirath; Stachowiak, Ewa K.; Tzanakakis, Emmanuel S.; Buck, Michael J.; Birkaya, Barbara; Stachowiak, Michal K.

    2015-01-01

    Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development. PMID:25923916

  5. Multiple NUCLEAR FACTOR Y transcription factors respond to abiotic stress in Brassica napus L.

    PubMed

    Xu, Li; Lin, Zhongyuan; Tao, Qing; Liang, Mingxiang; Zhao, Gengmao; Yin, Xiangzhen; Fu, Ruixin

    2014-01-01

    Members of the plant NUCLEAR FACTOR Y (NF-Y) family are composed of the NF-YA, NF-YB, and NF-YC subunits. In Brassica napus (canola), each of these subunits forms a multimember subfamily. Plant NF-Ys were reported to be involved in several abiotic stresses. In this study, we demonstrated that multiple members of thirty three BnNF-Ys responded rapidly to salinity, drought, or ABA treatments. Transcripts of five BnNF-YAs, seven BnNF-YBs, and two BnNF-YCs were up-regulated by salinity stress, whereas the expression of thirteen BnNF-YAs, ten BnNF-YBs, and four BnNF-YCs were induced by drought stress. Under NaCl treatments, the expression of one BnNF-YA10 and four NF-YBs (BnNF-YB3, BnNF-YB7, BnNF-YB10, and BnNF-YB14) were greatly increased. Under PEG treatments, the expression levels of four NF-YAs (BnNF-YA9, BnNF-YA10, BnNF-YA11, and BnNF-YA12) and five NF-YBs (BnNF-YB1, BnNF-YB8, BnNF-YB10, BnNF-YB13, and BnNF-YB14) were greatly induced. The expression profiles of 20 of the 27 salinity- or drought-induced BnNF-Ys were also affected by ABA treatment. The expression levels of six NF-YAs (BnNF-YA1, BnNF-YA7, BnNF-YA8, BnNF-YA9, BnNF-YA10, and BnNF-YA12) and seven BnNF-YB members (BnNF-YB2, BnNF-YB3, BnNF-YB7, BnNF-YB10, BnNF-YB11, BnNF-YB13, and BnNF-YB14) and two NF-YC members (BnNF-YC2 and BnNF-YC3) were greatly up-regulated by ABA treatments. Only a few BnNF-Ys were inhibited by the above three treatments. Several NF-Y subfamily members exhibited collinear expression patterns. The promoters of all stress-responsive BnNF-Ys harbored at least two types of stress-related cis-elements, such as ABRE, DRE, MYB, or MYC. The cis-element organization of BnNF-Ys was similar to that of Arabidopsis thaliana, and the promoter regions exhibited higher levels of nucleotide sequence identity with Brassica rapa than with Brassica oleracea. This work represents an entry point for investigating the roles of canola NF-Y proteins during abiotic stress responses and provides insight into

  6. Multiple NUCLEAR FACTOR Y transcription factors respond to abiotic stress in Brassica napus L.

    PubMed

    Xu, Li; Lin, Zhongyuan; Tao, Qing; Liang, Mingxiang; Zhao, Gengmao; Yin, Xiangzhen; Fu, Ruixin

    2014-01-01

    Members of the plant NUCLEAR FACTOR Y (NF-Y) family are composed of the NF-YA, NF-YB, and NF-YC subunits. In Brassica napus (canola), each of these subunits forms a multimember subfamily. Plant NF-Ys were reported to be involved in several abiotic stresses. In this study, we demonstrated that multiple members of thirty three BnNF-Ys responded rapidly to salinity, drought, or ABA treatments. Transcripts of five BnNF-YAs, seven BnNF-YBs, and two BnNF-YCs were up-regulated by salinity stress, whereas the expression of thirteen BnNF-YAs, ten BnNF-YBs, and four BnNF-YCs were induced by drought stress. Under NaCl treatments, the expression of one BnNF-YA10 and four NF-YBs (BnNF-YB3, BnNF-YB7, BnNF-YB10, and BnNF-YB14) were greatly increased. Under PEG treatments, the expression levels of four NF-YAs (BnNF-YA9, BnNF-YA10, BnNF-YA11, and BnNF-YA12) and five NF-YBs (BnNF-YB1, BnNF-YB8, BnNF-YB10, BnNF-YB13, and BnNF-YB14) were greatly induced. The expression profiles of 20 of the 27 salinity- or drought-induced BnNF-Ys were also affected by ABA treatment. The expression levels of six NF-YAs (BnNF-YA1, BnNF-YA7, BnNF-YA8, BnNF-YA9, BnNF-YA10, and BnNF-YA12) and seven BnNF-YB members (BnNF-YB2, BnNF-YB3, BnNF-YB7, BnNF-YB10, BnNF-YB11, BnNF-YB13, and BnNF-YB14) and two NF-YC members (BnNF-YC2 and BnNF-YC3) were greatly up-regulated by ABA treatments. Only a few BnNF-Ys were inhibited by the above three treatments. Several NF-Y subfamily members exhibited collinear expression patterns. The promoters of all stress-responsive BnNF-Ys harbored at least two types of stress-related cis-elements, such as ABRE, DRE, MYB, or MYC. The cis-element organization of BnNF-Ys was similar to that of Arabidopsis thaliana, and the promoter regions exhibited higher levels of nucleotide sequence identity with Brassica rapa than with Brassica oleracea. This work represents an entry point for investigating the roles of canola NF-Y proteins during abiotic stress responses and provides insight into

  7. Identification of a nuclear transport inhibitory signal (NTIS) in the basic domain of HIV-1 Vif protein.

    PubMed

    Friedler, A; Zakai, N; Karni, O; Friedler, D; Gilon, C; Loyter, A

    1999-06-11

    The HIV-1 auxiliary protein Vif contains a basic domain within its sequence. This basic region,90RKKR93, is similar to the prototypic nuclear localization signal (NLS). However, Vif is not a nuclear protein and does not function in the nucleus. Here we have studied the karyophilic properties of this basic region. We have synthesized peptides corresponding to this positively charged NLS-like region and observed that these peptides inhibited nuclear transport via the importin pathway in vitro with IC50values in the micromolar range. Inhibition was observed only with peptides derived from the positively charged region, but not from other regions of the Vif protein, showing sequence specificity. On the other hand, the Vif inhibitory peptide Vif88-98 did not confer karyophilic properties when conjugated to BSA. The inactive Vif conjugate and the active SV40-NLS-BSA conjugate both contained a similar number of peptides conjugated to each BSA molecule, as was determined by amino acid analysis of the peptide-BSA conjugates. Thus, the lack of nuclear import of the Vif peptide-BSA conjugate cannot be attributed to insufficient number of conjugated peptide molecules per BSA molecule. Our results suggest that the HIV-1 Vif protein carries an NLS-like sequence that inhibits, but does not mediate, nuclear import via the importin pathway. We have termed such signals as nuclear transport inhibitory signals (NTIS). The possible role of NTIS in controlling nuclear uptake, and specifically during virus infection, is discussed herein. Our results raise the possibility that NLS-like sequences of certain low molecular weight viral proteins may serve as regulators of nucleocytoplasmic trafficking and not neccessarily as mediators of nuclear import.

  8. Factors influencing the trans-membrane transport of n-octadecane by Pseudomonas sp. DG17

    PubMed Central

    Hua, Fei; Wang, Hong Qi; Zhao, Yi Cun

    2014-01-01

    In soil bioremediation techniques, the trans-membrane transport of hydrocarbons across the cell membrane is a new and complex point of understanding the process of hydrocarbons biodegradation. In this study, the effect of different environmental factors, including substrate concentration, bacterial inoculums, pH, salinity, substrate analogues and nutrients, on the transport of [14C]n-octadecane by Pseudomonas sp. DG17 was investigated. The results showed that cellular [14C]n-octadecane levels increased along with the increase in the substrate concentration. However, the trans-membrane transport of [14C]n-octadecane was a saturable process in the case of equal amounts of inoculum (biomass). The highest concentration of accumulated [14C]n-octadecane was 0.51 μmol mg−1 ± 0.028 μmol mg−1 after incubation for 20 min. Meanwhile, the cellular n-octadecane concentration decreased along with the biomass increase, and reached a stable level. Acidic/alkaline conditions, high salinity, and supplement of substrate analogues could inhibit the transport of [14C]n-octadecane by Pseudomonas sp. DG17, whereas nitrogen or phosphorus deficiency did not influence this transport. The results suggested that trans-membrane transport of octadecane depends on both the substrate concentration and the microorganism biomass, and extreme environmental conditions could influence the biodegradation ability of microorganisms through inhibiting the transport of extracellular octadecane. PMID:26740764

  9. Extended Burnup Credit for BWR Spent Nuclear Fuel in Storage and Transportation Systems

    SciTech Connect

    Ade, Brian J; Bowman, Stephen M; Gauld, Ian C; Ilas, Germina; Martinez, J. S.

    2015-01-01

    [Full Text] Oak Ridge National Laboratory and the United States Nuclear Regulatory Commission have initiated a multiyear project to investigate the application of burnup credit (BUC) for boiling-water reactor (BWR) fuel in storage and transportation casks. This project includes two phases. The first phase investigates the applicability of peak reactivity methods currently used for spent fuel pools to spent fuel storage and transportation casks and the validation of reactivity (keff) calculations and depleted fuel compositions. The second phase focuses on extending BUC beyond peak reactivity. This paper documents work performed to date, investigating some aspects of extended BUC, and it also describes the plan to complete the evaluations. The technical basis for application of peak reactivity methods to BWR fuel in storage and transportation systems is presented in a companion paper. Two reactor operating parameters are being evaluated to establish an adequate basis for extended BWR BUC, including investigation of the axial void profile effect and the effect of control blade utilization during operation. A detailed analysis of core simulator data for one cycle of an operating BWR plant was performed to determine the range of void profiles and the variability of the profile experienced during irradiation. While a single cycle does not provide complete data, the data obtained are sufficient to use to determine the primary effects and identify conservative modeling approaches. Using data resulting from a single cycle, the axial void profile is studied by first determining the temporal fidelity necessary in depletion modeling, and then using multiple void profiles to examine the effect of the void profile on cask reactivity. The results of these studies are being used to develop recommendations for conservatively modeling the void profile effects for BWR depletion calculations. The second operational parameter studied is control blade exposure. Control blades

  10. Correlated Biofilm Imaging, Transport and Metabolism Measurements via Combined Nuclear Magnetic Resonance and Confocal Microscopy

    SciTech Connect

    Mclean, Jeffrey S.; Ona, Ositadinma; Majors, Paul D.

    2008-02-18

    Bacterial biofilms are complex, three-dimensional, communities that are found nearly everywhere in nature1 and are being recognized as the cause of treatment-resistant infections1 2. Advanced methods are required to characterize their collective and spatial patterns of metabolism however most techniques are invasive or destructive. Here we describe the use of a combined confocal laser scanning microscopy (CLSM) and nuclear magnetic resonance (NMR) microscopy system to monitor structure, mass transport, and metabolism in active biofilms. Non-invasive NMR methods provide macroscopic structure along with spatially-resolved metabolite profiles and diffusion measurements. CLSM enables monitoring of cells by fluorescent protein reporters to investigate biofilm structure and gene expression concurrently. A planar sample chamber design facilitates depth-resolved measurements on 140 nL sample volumes under laminar flow conditions. The techniques and approaches described here are applicable to environmental and medically relevant microbial communities, thus providing key metabolic information for promoting beneficial biofilms and treating associated diseases.

  11. A simplified model for calculating atmospheric radionuclide transport and early health effects from nuclear reactor accidents

    SciTech Connect

    Madni, I.K.; Cazzoli, E.G.; Khatib-Rahbar, M.

    1995-11-01

    During certain hypothetical severe accidents in a nuclear power plant, radionuclides could be released to the environment as a plume. Prediction of the atmospheric dispersion and transport of these radionuclides is important for assessment of the risk to the public from such accidents. A simplified PC-based model was developed that predicts time-integrated air concentration of each radionuclide at any location from release as a function of time integrated source strength using the Gaussian plume model. The solution procedure involves direct analytic integration of air concentration equations over time and position, using simplified meteorology. The formulation allows for dry and wet deposition, radioactive decay and daughter buildup, reactor building wake effects, the inversion lid effect, plume rise due to buoyancy or momentum, release duration, and grass height. Based on air and ground concentrations of the radionuclides, the early dose to an individual is calculated via cloudshine, groundshine, and inhalation. The model also calculates early health effects based on the doses. This paper presents aspects of the model that would be of interest to the prediction of environmental flows and their public consequences.

  12. Assessing State Nuclear Weapons Proliferation: Using Bayesian Network Analysis of Social Factors

    SciTech Connect

    Coles, Garill A.; Brothers, Alan J.; Olson, Jarrod; Whitney, Paul D.

    2010-04-16

    A Bayesian network (BN) model of social factors can support proliferation assessments by estimating the likelihood that a state will pursue a nuclear weapon. Social factors including political, economic, nuclear capability, security, and national identity and psychology factors may play as important a role in whether a State pursues nuclear weapons as more physical factors. This paper will show how using Bayesian reasoning on a generic case of a would-be proliferator State can be used to combine evidence that supports proliferation assessment. Theories and analysis by political scientists can be leveraged in a quantitative and transparent way to indicate proliferation risk. BN models facilitate diagnosis and inference in a probabilistic environment by using a network of nodes and acyclic directed arcs between the nodes whose connections, or absence of, indicate probabilistic relevance, or independence. We propose a BN model that would use information from both traditional safeguards and the strengthened safeguards associated with the Additional Protocol to indicate countries with a high risk of proliferating nuclear weapons. This model could be used in a variety of applications such a prioritization tool and as a component of state safeguards evaluations. This paper will discuss the benefits of BN reasoning, the development of Pacific Northwest National Laboratory’s (PNNL) BN state proliferation model and how it could be employed as an analytical tool.

  13. Nuclear fractal dimension as a prognostic factor in oral squamous cell carcinoma.

    PubMed

    Goutzanis, L; Papadogeorgakis, N; Pavlopoulos, P M; Katti, K; Petsinis, V; Plochoras, I; Pantelidaki, C; Kavantzas, N; Patsouris, E; Alexandridis, C

    2008-04-01

    Strong theoretical reasons exist for using fractal geometry in measurements of natural objects, including most objects studied in pathology. Indeed, fractal dimension provides a more precise and theoretically more appropriate approximation of their structure properties and especially their shape complexity. The aim of our study was to evaluate the nuclear fractal dimension (FD) in tissue specimens from patients with oral cavity carcinomas in order to assess its potential value as prognostic factor. Relationships between FD and other factors including clinicopathologic characteristics were also investigated. Histological sections from 48 oral squamous cell carcinomas as well as from 17 non-malignant mucosa specimens were stained with Hematoxylin-Eosin for pathological examination and with Feulgen for nuclear complexity evaluation. The sections were evaluated by image analysis using fractal analysis software to quantify nuclear FD by the box-counting method. Carcinomas presented higher mean values of FD compared to normal mucosa. Well differentiated neoplasms had lower FD values than poorly differentiated ones. FD was significantly correlated with the nuclear size. Patients with FD lower than the median value of the sample had statistically significant higher survival rates. Within the sample of patients studied, FD was proved to be an independent prognostic factor of survival in oral cancer patients. In addition this study provides evidence that there are several statistically significant correlations between FD and other morphometric characteristics or clinicopathologic factors in oral squamous cell carcinomas. PMID:17692559

  14. Information needs for siting new, and evaluating current, nuclear facilities: ecology, fate and transport, and human health.

    PubMed

    Burger, Joanna; Clarke, James; Gochfeld, Michael

    2011-01-01

    The USA is entering an era of energy diversity, and increasing nuclear capacity and concerns focus on accidents, security, waste, and pollution. Physical buffers that separate outsiders from nuclear facilities often support important natural ecosystems but may contain contaminants. The US Nuclear Regulatory Commission (NRC) licenses nuclear reactors; the applicant provides environmental assessments that serve as the basis for Environmental Impact Statements developed by NRC. We provide a template for the types of information needed for safe siting of nuclear facilities with buffers in three categories: ecological, fate and transport, and human health information that can be used for risk evaluations. Each item on the lists is an indicator for evaluation, and individual indicators can be selected for specific region. Ecological information needs include biodiversity (species, populations, communities) and structure and functioning of ecosystems, habitats, and landscapes, in addition to common, abundant, and unique species and endangered and rare ones. The key variables of fate and transport are sources of release for radionuclides and other chemicals, nature of releases (atmospheric vapors, subsurface liquids), features, and properties of environmental media (wind speed, direction and atmospheric stability, hydraulic gradient, hydraulic conductivity, groundwater chemistry). Human health aspects include receptor populations (demography, density, dispersion, and distance), potential pathways (drinking water sources, gardening, fishing), and exposure opportunities (lifestyle activities). For each of the three types of information needs, we expect that only a few of the indicators will be applicable to a particular site and that stakeholders should agree on a site-specific suite. PMID:20140506

  15. Information needs for siting new, and evaluating current, nuclear facilities: ecology, fate and transport, and human health.

    PubMed

    Burger, Joanna; Clarke, James; Gochfeld, Michael

    2011-01-01

    The USA is entering an era of energy diversity, and increasing nuclear capacity and concerns focus on accidents, security, waste, and pollution. Physical buffers that separate outsiders from nuclear facilities often support important natural ecosystems but may contain contaminants. The US Nuclear Regulatory Commission (NRC) licenses nuclear reactors; the applicant provides environmental assessments that serve as the basis for Environmental Impact Statements developed by NRC. We provide a template for the types of information needed for safe siting of nuclear facilities with buffers in three categories: ecological, fate and transport, and human health information that can be used for risk evaluations. Each item on the lists is an indicator for evaluation, and individual indicators can be selected for specific region. Ecological information needs include biodiversity (species, populations, communities) and structure and functioning of ecosystems, habitats, and landscapes, in addition to common, abundant, and unique species and endangered and rare ones. The key variables of fate and transport are sources of release for radionuclides and other chemicals, nature of releases (atmospheric vapors, subsurface liquids), features, and properties of environmental media (wind speed, direction and atmospheric stability, hydraulic gradient, hydraulic conductivity, groundwater chemistry). Human health aspects include receptor populations (demography, density, dispersion, and distance), potential pathways (drinking water sources, gardening, fishing), and exposure opportunities (lifestyle activities). For each of the three types of information needs, we expect that only a few of the indicators will be applicable to a particular site and that stakeholders should agree on a site-specific suite.

  16. Identification and characterization of potential discharge areas for radionuclide transport by groundwater from a nuclear waste repository in Sweden.

    PubMed

    Berglund, Sten; Bosson, Emma; Selroos, Jan-Olof; Sassner, Mona

    2013-05-01

    This paper describes solute transport modeling carried out as a part of an assessment of the long-term radiological safety of a planned deep rock repository for spent nuclear fuel in Forsmark, Sweden. Specifically, it presents transport modeling performed to locate and describe discharge areas for groundwater potentially carrying radionuclides from the repository to the surface where man and the environment could be affected by the contamination. The modeling results show that topography to large extent determines the discharge locations. Present and future lake and wetland objects are central for the radionuclide transport and dose calculations in the safety assessment. Results of detailed transport modeling focusing on the regolith and the upper part of the rock indicate that the identification of discharge areas and objects considered in the safety assessment is robust in the sense that it does not change when a more detailed model representation is used.

  17. Isospin transport and reaction mechanism in nuclear reactions in the range 20–40 MeV/n

    SciTech Connect

    Barlini, S. Piantelli, S.; Casini, G.; Olmi, A.; Bini, M.; Pasquali, G.; Poggi, G.; Stefanini, A. A.; Valdré, S.; Pastore, G.; Bougault, R.; Lopez, O.; Le Neindre, N.; Parlog, M.; Vient, E.; Bonnet, E.; Chibhi, A.; Frankland, J. D. [GANIL, CEA Borderie, B.; Rivet, M. F. [Institut de Physique Nucléaire, CNRS and others

    2015-10-15

    In recent years, many efforts have been devoted to the investigation of the isospin degree of freedom in nuclear reactions. Comparing systems involving partners with different N/Z, it has been possible to investigate the isospin transport process and its influence on the final products population. This can be then related to the symmetry energy term of the nuclear EOS. From the experimental point of view, this task requires detectors able to measure both charge and mass of the emitted products, in the widest possible range of energy and size of the fragments. With this objective, the FAZIA and GARFIELD+RCo apparatus have been used with success in some recent experiments.

  18. Isospin transport and reaction mechanism in nuclear reactions in the range 20-40 MeV/n

    NASA Astrophysics Data System (ADS)

    Barlini, S.; Piantelli, S.; Casini, G.; Olmi, A.; Bini, M.; Pasquali, G.; Poggi, G.; Stefanini, A. A.; Bougault, R.; Bonnet, E.; Borderie, B.; Chibhi, A.; Frankland, J. D.; Gruyer, D.; Lopez, O.; Le Neindre, N.; Parlog, M.; Rivet, M. F.; Vient, E.; Rosato, E.; Vigilante, M.; Bruno, M.; Marchi, T.; Morelli, L.; Cinausero, M.; Degerlier, M.; Gramegna, F.; Kozik, T.; Twarog, T.; Fabris, D.; Valdré, S.; Pastore, G.

    2015-10-01

    In recent years, many efforts have been devoted to the investigation of the isospin degree of freedom in nuclear reactions. Comparing systems involving partners with different N/Z, it has been possible to investigate the isospin transport process and its influence on the final products population. This can be then related to the symmetry energy term of the nuclear EOS. From the experimental point of view, this task requires detectors able to measure both charge and mass of the emitted products, in the widest possible range of energy and size of the fragments. With this objective, the FAZIA and GARFIELD+RCo apparatus have been used with success in some recent experiments.

  19. Critical Environmental Factors for Transportation Cycling in Children: A Qualitative Study Using Bike-Along Interviews

    PubMed Central

    Ghekiere, Ariane; Van Cauwenberg, Jelle; de Geus, Bas; Clarys, Peter; Cardon, Greet; Salmon, Jo; De Bourdeaudhuij, Ilse; Deforche, Benedicte

    2014-01-01

    Background Environmental factors are found to influence transport-related physical activity, but have rarely been studied in relation with cycling for transport to various destinations in 10–12 yr old children. The current qualitative study used ‘bike-along interviews’ with children and parents to allow discussion of detailed environmental factors that may influence children's cycling for transport, while cycling in the participant's neighborhood. Methods Purposeful convenience sampling was used to recruit 35 children and one of their parents residing in (semi-) urban areas. Bike-along interviews were conducted to and from a randomly chosen destination (e.g. library) within a 15 minutes' cycle trip in the participant's neighborhood. Participants wore a GoPro camera to objectively assess environmental elements, which were subsequently discussed with participants. Content analysis and arising themes were derived using a grounded theory approach. Results The discussed environmental factors were categorized under traffic, urban design, cycling facilities, road design, facilities at destination, aesthetics, topography, weather, social control, stranger danger and familiar environment. Across these categories many environmental factors were (in)directly linked to road safety. This was illustrated by detailed discussions of the children's visibility, familiarity with specific traffic situations, and degree of separation, width and legibility of cycle facilities. Conclusion Road safety is of major concern in this 10–12 yr old study population. Bike-along interviews were able to identify new, detailed and context-specific physical environmental factors which could inform policy makers to promote children's cycling for transport. However, future studies should investigate whether hypothetical changes to such micro environmental features influence perceptions of safety and if this in turn could lead to changes in children's cycling for transport. PMID:25250738

  20. A single subunit of a heterotrimeric CCAAT-binding complex carries a nuclear localization signal: piggy back transport of the pre-assembled complex to the nucleus.

    PubMed

    Steidl, Stefan; Tüncher, André; Goda, Hideya; Guder, Corina; Papadopoulou, Natalia; Kobayashi, Tetsuo; Tsukagoshi, Norihiro; Kato, Masashi; Brakhage, Axel A

    2004-09-10

    An unresolved question concerns the nuclear localization of the heterotrimeric CCAAT-binding complex, which is evolutionarily conserved in eukaryotic organisms including fungi, plants and mammals. All three subunits are necessary for DNA binding. In the filamentous fungus Aspergillus nidulans the corresponding complex was designated AnCF (A.nidulans CCAAT-binding factor). AnCF consists of the HapB, HapC and HapE subunits. Here, by using various green fluorescent protein constructs, a nuclear localization signal sequence (NLS) of the HapB protein was identified, outside of the evolutionarily conserved domain. HapB-EGFP was transported into the nucleus in both DeltahapC and DeltahapE strains, indicating that its NLS interacts with the import machinery independently of the other Hap subunits. In contrast, HapC-EGFP did not enter the nucleus in the absence of HapE or HapB. A similar finding was made for HapE-EGFP, which did not localize to the nucleus in the absence of HapC or HapB. Addition of the HapB-NLS to either HapC or HapE led to nuclear localization of the respective protein fusions, indicating that both HapC and HapE lack a functional NLS. Furthermore, these data strongly suggest that HapC and HapE have first to form a heterodimer and can be transported only as a heterodimer via the HapB protein into the nucleus. Therefore, the HapB subunit is the primary cargo for the import machinery, while HapC and HapE are transported to the nucleus only as a heterodimer and in complex with HapB via a piggy back mechanism. This enables the cell to provide equimolar concentrations of all subunits to the nucleus.

  1. Diversity in the signals required for nuclear accumulation of U snRNPs and variety in the pathways of nuclear transport

    PubMed Central

    1991-01-01

    The requirements for nuclear targeting of a number of U snRNAs have been studied by analyzing the behavior of in vitro-generated transcripts after microinjection into the cytoplasm of Xenopus oocytes. Like the previously studied U1 snRNA, U2 snRNA is excluded from the nucleus when it does not have the 2,2,7mGpppN cap structure typical of the RNA polymerase II (pol II)-transcribed U snRNAs. Surprisingly, two other pol II-transcribed U snRNAs, U4 and U5, have a much less stringent requirement for the trimethyl cap structure. The gamma- monomethyl triphosphate cap structure of the RNA polymerase III- transcribed U6 snRNA, on the other hand, is shown not to play a role in nuclear targeting. Wheat germ agglutinin, which is known to prevent the import of many proteins into the nucleus, inhibits nuclear uptake of U6, but not of U1 or U5 snRNAs. Conversely, a 2,2,7mGpppG dinucleotide analogue of the trimethyl cap structure inhibits transport of the pol II U snRNAs, but does not detectably affect the transport of either U6 snRNA or a karyophilic protein. From these results it can be deduced that U6 enters the nucleus by a pathway similar or identical to that used by karyophilic proteins. The composite nuclear localization signals of the trimethyl cap-containing U snRNPs, however, do not function in the same way as previously defined nuclear targeting signals. PMID:1827444

  2. Coefficient of variation of nuclear diameters as a prognostic factor in papillary thyroid carcinoma.

    PubMed

    Chang, T C; Kuo, S H; How, S W

    1991-12-01

    To determine whether the coefficient of variation (CV) of nuclear diameters can be used as a prognostic factor in papillary thyroid carcinoma, we reviewed fine needle aspiration smears with Riu's stain from 55 operated-on and pathologically verified cases with a median follow-up of 6.5 years. For each case we measured the nuclear diameters of 100 cancer cells by ocular micrometry and calculated the CV of the nuclear diameters. Then we correlated the CV with the clinical stage, recurrence and death. There was a positive correlation between the CV of the nuclear diameters and the clinical stage (r = .59, P less than .0001). Recurrent cases (n = 10) had a higher CV than did those without recurrence (n = 45) (18.04 +/- 4.1% [mean +/- SD] versus 13.2 +/- 2.7%, P less than .0005). All recurrent cases had a CV greater than 13%. The cases in which death occurred (n = 5) had a higher CV than did those with survival (n = 50) (20.1 +/- 4.9% versus 13.5 +/- 2.7%, P less than .0005). All cases in which death occurred had a CV greater than 15%. The extent of variation of nuclear diameters was one of the factors influencing prognosis in papillary thyroid carcinoma. It offers a prognostic adjunct to standard clinical and histologic analysis.

  3. Modeling and Simulation of Used Nuclear Fuel During Transportation with Consideration of Hydride Effects and Cyclic Fatigue

    SciTech Connect

    Chakraborty, Pritam; Sabharwall, Piyush; Spears, Robert Edward; Coleman, Justin Leigh; Sener, Kadir; Varma, Amit H.

    2015-09-30

    The objective of this work is to understand the integrity of Used Nuclear Fuel (UNF) during transportation. Previous analysis work has been performed to look at the integrity of UNF during transportation but these analyses have neglected to analyze the effect of hydrides and flaws (fracture mechanics models to capture radial cracking in the cladding). In this study, the clad regions of interest are near the pellet-pellet interfaces. These regions can experience more complex stress-states than the rest of the clad during cooling and have a greater possibility to develop radially reoriented hydrides during vacuum drying.

  4. Nuclear localization of Src-family tyrosine kinases is required for growth factor-induced euchromatinization

    SciTech Connect

    Takahashi, Akinori; Obata, Yuuki; Fukumoto, Yasunori; Nakayama, Yuji; Kasahara, Kousuke; Kuga, Takahisa; Higashiyama, Yukihiro; Saito, Takashi; Yokoyama, Kazunari K.; Yamaguchi, Naoto

    2009-04-15

    Src-family kinases (SFKs), which participate in various signaling events, are found at not only the plasma membrane but also several subcellular compartments, including the nucleus. Nuclear structural changes are frequently observed during transcription, cell differentiation, senescence, tumorigenesis, and cell cycle. However, little is known about signal transduction in the alteration of chromatin texture. Here, we develop a pixel imaging method for quantitatively evaluating chromatin structural changes. Growth factor stimulation increases euchromatic hypocondensation and concomitant heterochromatic hypercondensation in G{sub 1} phase, and the levels reach a plateau by 30 min, sustain for at least 5 h and return to the basal levels after 24 h. Serum-activated SFKs in the nucleus were more frequently detected in the euchromatin areas than the heterochromatin areas. Nuclear expression of kinase-active SFKs, but not unrelated Syk kinase, drastically increases both euchromatinization and heterochromatinization in a manner dependent on the levels of nuclear tyrosine phosphorylation. However, growth factor stimulation does not induce chromatin structural changes in SYF cells lacking SFKs, and reintroduction of one SFK member into SYF cells can, albeit insufficiently, induce chromatin structural changes. These results suggest that nuclear tyrosine phosphorylation by SFKs plays an important role in chromatin structural changes upon growth factor stimulation.

  5. Nuclear localization of platelet-activating factor receptor controls retinal neovascularization

    PubMed Central

    K Bhosle, Vikrant; Rivera, José Carlos; Zhou, Tianwei (Ellen); Omri, Samy; Sanchez, Melanie; Hamel, David; Zhu, Tang; Rouget, Raphael; Rabea, Areej Al; Hou, Xin; Lahaie, Isabelle; Ribeiro-da-Silva, Alfredo; Chemtob, Sylvain

    2016-01-01

    Platelet-activating factor (PAF) is a pleiotropic phospholipid with proinflammatory, procoagulant and angiogenic actions on the vasculature. We and others have reported the presence of PAF receptor (Ptafr) at intracellular sites such as the nucleus. However, mechanisms of localization and physiologic functions of intracellular Ptafr remain poorly understood. We hereby identify the importance of C-terminal motif of the receptor and uncover novel roles of Rab11a GTPase and importin-5 in nuclear translocation of Ptafr in primary human retinal microvascular endothelial cells. Nuclear localization of Ptafr is independent of exogenous PAF stimulation as well as intracellular PAF biosynthesis. Moreover, nuclear Ptafr is responsible for the upregulation of unique set of growth factors, including vascular endothelial growth factor, in vitro and ex vivo. We further corroborate the intracrine PAF signaling, resulting in angiogenesis in vivo, using Ptafr antagonists with distinct plasma membrane permeability. Collectively, our findings show that nuclear Ptafr translocates in an agonist-independent manner, and distinctive functions of Ptafr based on its cellular localization point to another dimension needed for pharmacologic selectivity of drugs. PMID:27462464

  6. The fluidity of the nuclear envelope lipid does not affect the rate of nucleocytoplasmic RNA transport in mammalian liver.

    PubMed

    Agutter, P S; Suckling, K E

    1982-03-29

    The effects of in vitro and in vivo modifications of nuclear envelope lipid on DNa leakage and on ATP-stimulated RNA release from isolated rat liver nuclei were investigated. The modifications included corn-oil feeding of the animals to alter the fatty acid composition of the lipids, phospholipase treatment of the isolated nuclei, and extraction of the total lipid with Triton X-100. Significant changes in lipid composition and approximate order parameter values of the spin-label 5-doxylstearate resulted, but there was no significant effect on RNA transport rate. It was concluded that the nuclear envelope lipid does not play any important part in nucleocytoplasmic RNA transport in mammalian liver.

  7. Analysis of atmospheric dispersion factors for building wakes at the Wolsung nuclear site in Korea.

    PubMed

    Jeong, Hyojoon; Park, Misun; Hwang, Wontae; Kim, Eunhan; Han, Moonhee

    2013-05-01

    The characteristics of atmospheric dispersion considering the building effects in the Wolsung nuclear site in Korea were studied using ISC-PRIME and ARCON96 models. The maximum 2-h average atmospheric dispersion factor (ADF) was six times larger when the building geometry was considered in ISC-PRIME and two times larger in the exclusion area boundary. Owing to different adjustments for wind speed by the stability class, the ADFs calculated using ARCON96 were smaller than those calculated using ISC-PRIME. Strategies for locating buildings need to be considered to maximise dispersion when planning for constructing several reactors and accessory buildings at the Wolsung nuclear site. PMID:23108599

  8. Analysis of atmospheric dispersion factors for building wakes at the Wolsung nuclear site in Korea.

    PubMed

    Jeong, Hyojoon; Park, Misun; Hwang, Wontae; Kim, Eunhan; Han, Moonhee

    2013-05-01

    The characteristics of atmospheric dispersion considering the building effects in the Wolsung nuclear site in Korea were studied using ISC-PRIME and ARCON96 models. The maximum 2-h average atmospheric dispersion factor (ADF) was six times larger when the building geometry was considered in ISC-PRIME and two times larger in the exclusion area boundary. Owing to different adjustments for wind speed by the stability class, the ADFs calculated using ARCON96 were smaller than those calculated using ISC-PRIME. Strategies for locating buildings need to be considered to maximise dispersion when planning for constructing several reactors and accessory buildings at the Wolsung nuclear site.

  9. Effect of insulin-like factors on glucose transport activity in unweighted rat skeletal muscle

    NASA Technical Reports Server (NTRS)

    Henriksen, Erik J.; Ritter, Leslie S.

    1993-01-01

    The effect of 3 or 6 days of unweighting on glucose transport activity, as assessed by 2-deoxyglucose uptake, in soleus strips stimulated by maximally effective concentrations of insulin, IGF-I, vanadate, or phospholipase C (PLC) is examined. Progressively increased responses to maximally effective doses of insulin or insulin-like growth factor were observed after 3 and 6 days of unweighting compared with weight matched control strips. Enhanced maximal responses to vanadate (6 days only) and PLC (3 and 6 days) were also observed. The data provide support for the existance of postreceptor binding mechanisms for the increased action of insulin on the glucose transport system in unweighted rat skeletal muscle.

  10. Disentangling steric and electrostatic factors in nanoscale transport through confined space.

    PubMed

    Buchsbaum, Steven F; Mitchell, Nick; Martin, Hugh; Wiggin, Matt; Marziali, Andre; Coveney, Peter V; Siwy, Zuzanna; Howorka, Stefan

    2013-08-14

    The voltage-driven passage of biological polymers through nanoscale pores is an analytically, technologically, and biologically relevant process. Despite various studies on homopolymer translocation there are still several open questions on the fundamental aspects of pore transport. One of the most important unresolved issues revolves around the passage of biopolymers which vary in charge and volume along their sequence. Here we exploit an experimentally tunable system to disentangle and quantify electrostatic and steric factors. This new, fundamental framework facilitates the understanding of how complex biopolymers are transported through confined space and indicates how their translocation can be slowed down to enable future sensing methods.

  11. 75 FR 43518 - Blue Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-26

    ... of Energy, Office of Nuclear Energy. ACTION: Notice of open meeting. SUMMARY: This notice announces..., DC 20585; telephone (202) 586-4243 or facsimile (202) 586- 0544; e-mail CommissionDFO@nuclear.energy... Independence Avenue, SW., Washington DC 20585, e-mail to CommissionDFO@nuclear.energy.gov , or post comments...

  12. Functional Impact of Corticotropin-Releasing Factor Exposure on Tau Phosphorylation and Axon Transport

    PubMed Central

    Le, Michelle H.; Weissmiller, April M.; Monte, Louise; Lin, Po Han; Hexom, Tia C.; Natera, Orlangie; Wu, Chengbiao; Rissman, Robert A.

    2016-01-01

    Stress exposure or increased levels of corticotropin-releasing factor (CRF) induce hippocampal tau phosphorylation (tau-P) in rodent models, a process that is dependent on the type-1 CRF receptor (CRFR1). Although these preclinical studies on stress-induced tau-P provide mechanistic insight for epidemiological work that identifies stress as a risk factor for Alzheimer’s disease (AD), the actual impact of stress-induced tau-P on neuronal function remains unclear. To determine the functional consequences of stress-induced tau-P, we developed a novel mouse neuronal cell culture system to explore the impact of acute (0.5hr) and chronic (2hr) CRF treatment on tau-P and integral cell processes such as axon transport. Consistent with in vivo reports, we found that chronic CRF treatment increased tau-P levels and caused globular accumulations of phosphorylated tau in dendritic and axonal processes. Furthermore, while both acute and chronic CRF treatment led to significant reduction in CREB activation and axon transport of brain-derived neurotrophic factor (BDNF), this was not the case with mitochondrial transport. Acute CRF treatment caused increased mitochondrial velocity and distance traveled in neurons, while chronic CRF treatment modestly decreased mitochondrial velocity and greatly increased distance traveled. These results suggest that transport of cellular energetics may take priority over growth factors during stress. Tau-P was required for these changes, as co-treatment of CRF with a GSK kinase inhibitor prevented CRF-induced tau-P and all axon transport changes. Collectively, our results provide mechanistic insight into the consequences of stress peptide-induced tau-P and provide an explanation for how chronic stress via CRF may lead to neuronal vulnerability in AD. PMID:26790099

  13. Binding, internalization, and retrograde transport of /sup 125/I-nerve growth factor in cultured rat sympathetic neurons

    SciTech Connect

    Claude, P.; Hawrot, E.; Dunis, D.A.; Campenot, R.B.

    1982-01-01

    Sympathetic neurons internalize nerve growth factor (NGF) and transport it retrogradely to their cell bodies where it appears to serve a trophic function in maintaining neuronal survival. We have characterized the binding, internalization, and retrograde transport of /sup 125/I-NGF by cultured rat sympathetic neurons. After 3 to 4 weeks in culture, sympathetic neurons possessed approximately 2 X 10(7) specific, cell surface NGF binding sites per neuron with an apparent affinity constant of 2 to 5 X 10(9) M. The density of binding sites on the plasma membrane of the neurites approximately twice that on the plasma membrane of the cell bodies. Because of the extensive network of neuronal processes, the neurites probably account for more than 99.5% of the total binding in mature cultures. Using electron microscope autoradiography, we localized the distribution of /sup 125/I-NGF in the cell body following a 1-hr exposure to /sup 125/I-NGF. The majority of silver grains were associated with lysosomal organelles, including secondary lysosomes, residual bodies, and multivesicular bodies (MVB). The MVB were the most heavily labeled, with a labeling density (L.D.) of 21, while the lysosomes had a L.D. of 3.1. To study the retrograde transport of /sup 125/I-NGF, neurons were grown in compartmentalized culture dishes and their distal processes were exposed to /sup 125/I-NGF. Radioactive material was transported to the cell bodies at the rate of approximately 3 mm/hr. The transport mechanism was sensitive to colchicine and was saturable with respect to NGF. After 8 hr of transport, when the radioactivity in the cell bodies had reached a steady state, the label again was localized primarily to the MVB (L.D. . 16.8) and the lysosomes (L.D. . 3.8). The nuclei were not labeled significantly and had an overall L.D. of 0.47. We saw no evidence for the accumulation of NGF by the nuclear membrane, the nucleolus, or chromatin.

  14. Trans-oceanic transport of 137Cs from the Fukushima nuclear accident and impact of hypothetical Fukushima-like events of future nuclear plants in Southern China.

    PubMed

    Wai, Ka-Ming; Yu, Peter K N

    2015-03-01

    A Lagrangian model was adopted to assess the potential impact of (137)Cs released from hypothetical Fukushima-like accidents occurring on three potential nuclear power plant sites in Southern China in the near future (planned within 10 years) in four different seasons. The maximum surface (0-500 m) (137)Cs air concentrations would be reached 10 Bq m(-3) near the source, comparable to the Fukushima case. In January, Southeast Asian countries would be mostly affected by the radioactive plume due to the effects of winter monsoon. In April, the impact would be mainly on Southern and Northern China. Debris of radioactive plume (~1 mBq m(-3)) would carry out long-range transport to North America. The area of influence would be the smallest in July due to the frequent and intense wet removal events by trough of low pressure and tropical cyclone. The maximum worst-case areas of influence were 2382000, 2327000, 517000 and 1395000 km(2) in January, April, July and October, respectively. Prior to the above calculations, the model was employed to simulate the trans-oceanic transport of (137)Cs from the Fukushima nuclear accident. Observed and modeled (137)Cs concentrations were comparable. Sensitivity runs were performed to optimize the wet scavenging parameterization. The adoption of higher-resolution (1° × 1°) meteorological fields improved the prediction. The computed large-scale plume transport pattern over the Pacific Ocean was compared with that reported in the literature. PMID:25474170

  15. Trans-oceanic transport of 137Cs from the Fukushima nuclear accident and impact of hypothetical Fukushima-like events of future nuclear plants in Southern China.

    PubMed

    Wai, Ka-Ming; Yu, Peter K N

    2015-03-01

    A Lagrangian model was adopted to assess the potential impact of (137)Cs released from hypothetical Fukushima-like accidents occurring on three potential nuclear power plant sites in Southern China in the near future (planned within 10 years) in four different seasons. The maximum surface (0-500 m) (137)Cs air concentrations would be reached 10 Bq m(-3) near the source, comparable to the Fukushima case. In January, Southeast Asian countries would be mostly affected by the radioactive plume due to the effects of winter monsoon. In April, the impact would be mainly on Southern and Northern China. Debris of radioactive plume (~1 mBq m(-3)) would carry out long-range transport to North America. The area of influence would be the smallest in July due to the frequent and intense wet removal events by trough of low pressure and tropical cyclone. The maximum worst-case areas of influence were 2382000, 2327000, 517000 and 1395000 km(2) in January, April, July and October, respectively. Prior to the above calculations, the model was employed to simulate the trans-oceanic transport of (137)Cs from the Fukushima nuclear accident. Observed and modeled (137)Cs concentrations were comparable. Sensitivity runs were performed to optimize the wet scavenging parameterization. The adoption of higher-resolution (1° × 1°) meteorological fields improved the prediction. The computed large-scale plume transport pattern over the Pacific Ocean was compared with that reported in the literature.

  16. The ins and outs of nuclear re-export of retrogradely transported tRNAs in Saccharomyces cerevisiae.

    PubMed

    Pierce, Jacqueline B; Eswara, Manoja Bk; Mangroo, Dev

    2010-01-01

    In Saccharomyces cerevisiae intron-containing pre-tRNAs are exported from the nucleus to the cytoplasm for removal of the introns, and the spliced tRNAs are returned to the nucleus for reasons that are not understood. The re-imported spliced tRNAs are then subjected to aminoacylation in the nucleolus to ensure that they are functional prior to re-export to the cytoplasm. Previous studies have shown that re-imported spliced tRNAs and mature tRNAs made entirely in the nucleus from intronless precursors are retained in the nucleus of S. cerevisiae in response to glucose, amino acid, nitrogen or inorganic phosphate deprivation. Contrary to these studies, we recently reported that starvation of S. cerevisiae of amino acids or nitrogen results in nuclear accumulation of re-imported spliced tRNAs, but not tRNAs made from intronless precursors. This finding suggests that separate pathways are used for nuclear export of retrogradely transported spliced tRNAs and tRNAs made from intronless pre-tRNAs. In addition, the data support the conclusion that the nuclear re-export pathway for retrogradely transported spliced tRNAs, but not the pathway responsible for nuclear export of tRNAs derived from intronless precursors is regulated during amino acid or nitrogen starvation. This regulation appears to occur at a step after the re-imported spliced tRNAs have undergone aminoacylation quality assurance and, in part, involves the TORC1 signalling pathway. Moreover, it was established that Utp9p is an intranuclear component that only facilitates nuclear re-export of retrogradely transported spliced tRNAs by the β-karyopherin Msn5p. Utp9p acts in concert with Utp8p, a key player in nuclear tRNA export in S. cerevisiae, to translocate aminoacylated re-imported spliced tRNAs from the nucleolus to Msn5p and assist with formation of the Msn5p-tRNA-Gsp1p-GTP export complex. This pathway, however, is not the only one responsible for nuclear re-export of retrogradely transported spliced tRNAs.

  17. Comparison of Integrated Radiation Transport Models with TEPC Measurements for the Average Quality Factors in Spaceflights

    NASA Technical Reports Server (NTRS)

    Kim, Myung-Hee Y.; Nikjoo, Hooshang; Dicello, John F.; Pisacane, Vincent; Cucinotta, Francis A.

    2007-01-01

    radiation type (Z = 1 to 28). Because the anomalous response has been observed at large event sizes in the experiment due to the escape of energy out of sensitive volume by delta-rays and the entry of delta-rays from the high-density wall into the low-density gas-volume cavity, Monte Carlo simulation was also made for the response of a walled-TEPC with wall thickness 2 mm and density 1 g/cm(exp 3). The radius of cavity was set to 6.35 mm and a gas density 7.874 x 10(exp -5) g/cm(exp 3). The response of the walled- and the wall-less counters were compared. The average quality factor Q(sub ave)(y) for trapped protons on STS-89 demonstrated the good agreement between the model calculations and flight TEPC data as shown. Using an integrated space radiation model (this includes the transport codes HZETRN and BRYNTRN, the quantum nuclear interaction model QMSFRG) and the resultant response distribution functions of walled-TEPC from Monte-Carlo track simulations, we compared model calculations with walled-TEPC measurements from NASA missions in LEO and made predictions for the lunar and the Mars missions. The Q(sub ave)(y) values for the trapped or the solar protons ranged from 1.9-2.5. This over-estimates the Qave(LET) values which ranged from 1.4-1.6. Both quantities increase with shield thickness due to nuclear fragmentation. The Q(sub ave)(LET) for the complete GCR spectra was found to be 3.5-4.5, while flight TEPCs measured 2.9-3.4 for Q(sub ave)(y). The GCR values are decreasing with the shield thickness. Our analysis for a proper interpretation of data supports the use of TEPCs for monitoring space radiation environment.

  18. Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor.

    PubMed

    Gonzalez, Eva; Flier, Emily; Molle, Dorothee; Accili, Domenico; McGraw, Timothy E

    2011-06-21

    Insulin resistance is a component of the metabolic syndrome and Type 2 diabetes. It has been recently shown that in liver insulin resistance is not complete. This so-called selective insulin resistance is characterized by defective insulin inhibition of hepatic glucose output while insulin-induced lipogenesis is maintained. How this occurs and whether uncoupled insulin action develops in other tissues is unknown. Here we show in a model of chronic hyperinsulinemia that adipocytes develop selective insulin resistance in which translocation of the GLUT4 glucose transporter to the cell surface is blunted yet nuclear exclusion of the FoxO1 transcription factor is preserved, rendering uncoupled insulin-controlled carbohydrate and lipid metabolisms. We found that in adipocytes FoxO1 nuclear exclusion has a lower half-maximal insulin dose than GLUT4 translocation, and it is because of this inherent greater sensitivity that control of FoxO1 by physiological insulin concentrations is maintained in adipocytes with compromised insulin signaling. Pharmacological and genetic interventions revealed that insulin regulates GLUT4 and FoxO1 through the PI3-kinase isoform p110α, although FoxO1 showed higher sensitivity to p110α activity than GLUT4. Transient down-regulation and overexpression of Akt isoforms in adipocytes demonstrated that insulin-activated PI3-kinase signals to GLUT4 primarily through Akt2 kinase, whereas Akt1 and Akt2 signal to FoxO1. We propose that the lower threshold of insulin activity for FoxO1's nuclear exclusion is in part due to its regulation by both Akt isoforms. Identification of uncoupled insulin action in adipocytes suggests this condition might be a general phenomenon of insulin target tissues contributing to insulin resistance's pathophysiology.

  19. Analysis of human factors effects on the safety of transporting radioactive waste materials: Technical report

    SciTech Connect

    Abkowitz, M.D.; Abkowitz, S.B.; Lepofsky, M.

    1989-04-01

    This report examines the extent of human factors effects on the safety of transporting radioactive waste materials. It is seen principally as a scoping effort, to establish whether there is a need for DOE to undertake a more formal approach to studying human factors in radioactive waste transport, and if so, logical directions for that program to follow. Human factors effects are evaluated on driving and loading/transfer operations only. Particular emphasis is placed on the driving function, examining the relationship between human error and safety as it relates to the impairment of driver performance. Although multi-modal in focus, the widespread availability of data and previous literature on truck operations resulted in a primary study focus on the trucking mode from the standpoint of policy development. In addition to the analysis of human factors accident statistics, the report provides relevant background material on several policies that have been instituted or are under consideration, directed at improving human reliability in the transport sector. On the basis of reported findings, preliminary policy areas are identified. 71 refs., 26 figs., 5 tabs.

  20. Correlated biofilm imaging, transport and metabolism measurements via combined nuclear magnetic resonance and confocal microscopy

    PubMed Central

    McLean, Jeffrey S; Ona, Ositadinma N; Majors, Paul D

    2015-01-01

    Bacterial biofilms are complex, three-dimensional communities found nearly everywhere in nature and are also associated with many human diseases. Detailed metabolic information is critical to understand and exploit beneficial biofilms as well as combat antibiotic-resistant, disease-associated forms. However, most current techniques used to measure temporal and spatial metabolite profiles in these delicate structures are invasive or destructive. Here, we describe imaging, transport and metabolite measurement methods and their correlation for live, non-invasive monitoring of biofilm processes. This novel combination of measurements is enabled by the use of an integrated nuclear magnetic resonance (NMR) and confocal laser scanning microscope (CLSM). NMR methods provide macroscopic structure, metabolic pathway and rate data, spatially resolved metabolite concentrations and water diffusion profiles within the biofilm. In particular, current depth-resolved spectroscopy methods are applied to detect metabolites in 140–190 nl volumes within biofilms of the dissimilatory metal-reducing bacterium Shewanella oneidensis strain MR-1 and the oral bacterium implicated in caries disease, Streptococcus mutans strain UA159. The perfused sample chamber also contains a transparent optical window allowing for the collection of complementary fluorescence information using a unique, in-magnet CLSM. In this example, the entire three-dimensional biofilm structure was imaged using magnetic resonance imaging. This was then correlated to a fluorescent CLSM image by employing a green fluorescent protein reporter construct of S. oneidensis. Non-invasive techniques such as described here, which enable measurements of dynamic metabolic processes, especially in a depth-resolved fashion, are expected to advance our understanding of processes occurring within biofilm communities. PMID:18253132

  1. The Complexity of Vesicle Transport Factors in Plants Examined by Orthology Search

    PubMed Central

    Mirus, Oliver; Scharf, Klaus-Dieter; Fragkostefanakis, Sotirios; Schleiff, Enrico

    2014-01-01

    Vesicle transport is a central process to ensure protein and lipid distribution in eukaryotic cells. The current knowledge on the molecular components and mechanisms of this process is majorly based on studies in Saccharomyces cerevisiae and Arabidopsis thaliana, which revealed 240 different proteinaceous factors either experimentally proven or predicted to be involved in vesicle transport. In here, we performed an orthologue search using two different algorithms to identify the components of the secretory pathway in yeast and 14 plant genomes by using the ‘core-set’ of 240 factors as bait. We identified 4021 orthologues and (co-)orthologues in the discussed plant species accounting for components of COP-II, COP-I, Clathrin Coated Vesicles, Retromers and ESCRTs, Rab GTPases, Tethering factors and SNAREs. In plants, we observed a significantly higher number of (co-)orthologues than yeast, while only 8 tethering factors from yeast seem to be absent in the analyzed plant genomes. To link the identified (co-)orthologues to vesicle transport, the domain architecture of the proteins from yeast, genetic model plant A. thaliana and agriculturally relevant crop Solanum lycopersicum has been inspected. For the orthologous groups containing (co-)orthologues from yeast, A. thaliana and S. lycopersicum, we observed the same domain architecture for 79% (416/527) of the (co-)orthologues, which documents a very high conservation of this process. Further, publically available tissue-specific expression profiles for a subset of (co-)orthologues found in A. thaliana and S. lycopersicum suggest that some (co-)orthologues are involved in tissue-specific functions. Inspection of localization of the (co-)orthologues based on available proteome data or localization predictions lead to the assignment of plastid- as well as mitochondrial localized (co-)orthologues of vesicle transport factors and the relevance of this is discussed. PMID:24844592

  2. Neutron Transport and Nuclear Burnup Analysis for the Laser Inertial Confinement Fusion-Fission Energy (LIFE) Engine

    SciTech Connect

    Kramer, K J; Latkowski, J F; Abbott, R P; Boyd, J K; Powers, J J; Seifried, J E

    2008-10-24

    Lawrence Livermore National Laboratory is currently developing a hybrid fusion-fission nuclear energy system, called LIFE, to generate power and burn nuclear waste. We utilize inertial confinement fusion to drive a subcritical fission blanket surrounding the fusion chamber. It is composed of TRISO-based fuel cooled by the molten salt flibe. Low-yield (37.5 MJ) targets and a repetition rate of 13.3 Hz produce a 500 MW fusion source that is coupled to the subcritical blanket, which provides an additional gain of 4-8, depending on the fuel. In the present work, we describe the neutron transport and nuclear burnup analysis. We utilize standard analysis tools including, the Monte Carlo N-Particle (MCNP) transport code, ORIGEN2 and Monteburns to perform the nuclear design. These analyses focus primarily on a fuel composed of depleted uranium not requiring chemical reprocessing or enrichment. However, other fuels such as weapons grade plutonium and highly-enriched uranium are also under consideration. In addition, we have developed a methodology using {sup 6}Li as a burnable poison to replace the tritium burned in the fusion targets and to maintain constant power over the lifetime of the engine. The results from depleted uranium analyses suggest up to 99% burnup of actinides is attainable while maintaining full power at 2GW for more than five decades.

  3. Possible mechanisms and function of nuclear trafficking of the colony-stimulating factor-1 receptor.

    PubMed

    Rovida, Elisabetta; Dello Sbarba, Persio

    2014-10-01

    Receptor tyrosine kinases (RTK) have long being studied with respect to the "canonical" signaling. This includes ligand-induced activation of a receptor tyrosine kinase at the cell surface that leads to receptor dimerization, followed by its phosphorylation in the intracellular domain and activation. The activated receptor then recruits cytoplasmic signaling molecules including other kinases. Activation of the downstream signaling cascade frequently leads to changes in gene expression following nuclear translocation of downstream targets. However, RTK themselves may localize within the nucleus, as either full-length molecules or cleaved fragments, with or without their ligands. Significant differences in this mechanism have been reported depending on the individual RTK, cellular context or disease. Accumulating evidences indicate that the colony-stimulating factor-1 receptor (CSF-1R) may localize within the nucleus. To date, however, little is known about the mechanism of CSF-1R nuclear shuttling, as well as the functional role of nuclear CSF-1R.

  4. Nuclearly encoded splicing factors implicated in RNA splicing in higher plant organelles.

    PubMed

    de Longevialle, Andéol Falcon; Small, Ian D; Lurin, Claire

    2010-07-01

    Plant organelles arose from two independent endosymbiosis events. Throughout evolutionary history, tight control of chloroplasts and mitochondria has been gained by the nucleus, which regulates most steps of organelle genome expression and metabolism. In particular, RNA maturation, including RNA splicing, is highly dependent on nuclearly encoded splicing factors. Most introns in organelles are group II introns, whose catalytic mechanism closely resembles that of the nuclear spliceosome. Plant group II introns have lost the ability to self-splice in vivo and require nuclearly encoded proteins as cofactors. Since the first splicing factor was identified in chloroplasts more than 10 years ago, many other proteins have been shown to be involved in splicing of one or more introns in chloroplasts or mitochondria. These new proteins belong to a variety of different families of RNA binding proteins and provide new insights into ribonucleo-protein complexes and RNA splicing machineries in organelles. In this review, we describe how splicing factors, encoded by the nucleus and targeted to the organelles, take part in post-transcriptional steps in higher plant organelle gene expression. We go on to discuss the potential for these factors to regulate organelle gene expression.

  5. 41 CFR 102-117.175 - What factors do I consider to determine the mode of transportation?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false What factors do I... Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION TRANSPORTATION 117-TRANSPORTATION MANAGEMENT Shipping Freight § 102-117.175 What factors do...

  6. 41 CFR 102-117.175 - What factors do I consider to determine the mode of transportation?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What factors do I... Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION TRANSPORTATION 117-TRANSPORTATION MANAGEMENT Shipping Freight § 102-117.175 What factors do...

  7. 41 CFR 102-117.175 - What factors do I consider to determine the mode of transportation?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false What factors do I... Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION TRANSPORTATION 117-TRANSPORTATION MANAGEMENT Shipping Freight § 102-117.175 What factors do...

  8. 41 CFR 102-117.175 - What factors do I consider to determine the mode of transportation?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false What factors do I... Property Management Federal Property Management Regulations System (Continued) FEDERAL MANAGEMENT REGULATION TRANSPORTATION 117-TRANSPORTATION MANAGEMENT Shipping Freight § 102-117.175 What factors do...

  9. Establishing a value chain for human factors in nuclear power plantcontrol room modernization

    SciTech Connect

    Joe, Jeffrey Clark; Thomas, Kenneth David; Boring, Ronald Laurids

    2015-07-01

    Commercial nuclear power plants in the United States (U.S.) have operated reliably and efficiently for decades. With the life extensions of plants now being planned for operation beyond their original operating licenses, there are opportunities to achieve even greater efficiencies, while maintaining high operational reliabilities, with strategic, risk- and economically-informed, upgrades to plant systems and infrastructure. The U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) program supports the commercial nuclear industry’s modernization efforts through research and development (R&D) activities across many areas to help establish the technical and economic bases for modernization activities. The Advanced Instrumentation, Information, and Control Systems Technologies pathway is one R&D focus area for the LWRS program, and has researchers at Idaho National Laboratory working with select utility partners to use human factors and instrumentation and controls R&D to help modernize the plant’s main control room. However, some in the nuclear industry have not been as enthusiastic about using human factors R&D to inform life extension decision making. Part of the reason for this may stem from uncertainty decision-makers have regarding how human factors fits into the value chain for nuclear power plant control room modernization. This paper reviews past work that has attempted to demonstrate the value of human factors, and then describes the value chain concept, how it applies to control room modernization, and then makes a case for how and why human factors is an essential link in the modernization value chain.

  10. Nuclear Import of the Parsley bZIP Transcription Factor CPRF2 Is Regulated by Phytochrome Photoreceptors

    PubMed Central

    Kircher, Stefan; Wellmer, Frank; Nick, Peter; Rügner, Alexander; Schäfer, Eberhard; Harter, Klaus

    1999-01-01

    In plants, light perception by photoreceptors leads to differential expression of an enormous number of genes. An important step for differential gene expression is the regulation of transcription factor activities. To understand these processes in light signal transduction we analyzed the three well-known members of the common plant regulatory factor (CPRF) family from parsley (Petroselinum crispum). Here, we demonstrate that these CPRFs, which belong to the basic- region leucine-zipper (bZIP) domain-containing transcription factors, are differentially distributed within parsley cells, indicating different regulatory functions within the regulatory networks of the plant cell. In particular, we show by cell fractionation and immunolocalization approaches that CPRF2 is transported from the cytosol into the nucleus upon irradiation due to action of phytochrome photoreceptors. Two NH2-terminal domains responsible for cytoplasmic localization of CPRF2 in the dark were characterized by deletion analysis using a set of CPRF2-green fluorescent protein (GFP) gene fusion constructs transiently expressed in parsley protoplasts. We suggest that light-induced nuclear import of CPRF2 is an essential step in phytochrome signal transduction. PMID:9922448

  11. Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

    PubMed

    Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

    2010-05-21

    NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

  12. Featured Article: Nuclear export of opioid growth factor receptor is CRM1 dependent.

    PubMed

    Kren, Nancy P; Zagon, Ian S; McLaughlin, Patricia J

    2016-02-01

    Opioid growth factor receptor (OGFr) facilitates growth inhibition in the presence of its specific ligand opioid growth factor (OGF), chemically termed [Met(5)]-enkephalin. The function of the OGF-OGFr axis requires the receptor to translocate to the nucleus. However, the mechanism of nuclear export of OGFr is unknown. In this study, endogenous OGFr, as well as exogenously expressed OGFr-EGFP, demonstrated significant nuclear accumulation in response to leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export, suggesting that OGFr is exported in a CRM1-dependent manner. One consensus sequence for a nuclear export signal (NES) was identified. Mutation of the associated leucines, L217 L220 L223 and L225, to alanine resulted in decreased nuclear accumulation. NES-EGFP responded to LMB, indicating that this sequence is capable of functioning as an export signal in isolation. To determine why the sequence functions differently in isolation than as a full length protein, the localization of subNES was evaluated in the presence and absence of MG132, a potent inhibitor of proteosomal degradation. MG132 had no effect of subNES localization. The role of tandem repeats located at the C-terminus of OGFr was examined for their role in nuclear trafficking. Six of seven tandem repeats were removed to form deltaTR. DeltaTR localized exclusively to the nucleus indicating that the tandem repeats may contribute to the localization of the receptor. Similar to the loss of cellular proliferation activity (i.e. inhibition) recorded with subNES, deltaTR also demonstrated a significant loss of inhibitory activity indicating that the repeats may be integral to receptor function. These experiments reveal that OGFr contains one functional NES, L217 L220 L223 and L225 and can be exported from the nucleus in a CRM1-dependent manner.

  13. Featured Article: Nuclear export of opioid growth factor receptor is CRM1 dependent

    PubMed Central

    Kren, Nancy P; Zagon, Ian S

    2015-01-01

    Opioid growth factor receptor (OGFr) facilitates growth inhibition in the presence of its specific ligand opioid growth factor (OGF), chemically termed [Met5]-enkephalin. The function of the OGF-OGFr axis requires the receptor to translocate to the nucleus. However, the mechanism of nuclear export of OGFr is unknown. In this study, endogenous OGFr, as well as exogenously expressed OGFr-EGFP, demonstrated significant nuclear accumulation in response to leptomycin B (LMB), an inhibitor of CRM1-dependent nuclear export, suggesting that OGFr is exported in a CRM1-dependent manner. One consensus sequence for a nuclear export signal (NES) was identified. Mutation of the associated leucines, L217 L220 L223 and L225, to alanine resulted in decreased nuclear accumulation. NES-EGFP responded to LMB, indicating that this sequence is capable of functioning as an export signal in isolation. To determine why the sequence functions differently in isolation than as a full length protein, the localization of subNES was evaluated in the presence and absence of MG132, a potent inhibitor of proteosomal degradation. MG132 had no effect of subNES localization. The role of tandem repeats located at the C-terminus of OGFr was examined for their role in nuclear trafficking. Six of seven tandem repeats were removed to form deltaTR. DeltaTR localized exclusively to the nucleus indicating that the tandem repeats may contribute to the localization of the receptor. Similar to the loss of cellular proliferation activity (i.e. inhibition) recorded with subNES, deltaTR also demonstrated a significant loss of inhibitory activity indicating that the repeats may be integral to receptor function. These experiments reveal that OGFr contains one functional NES, L217 L220 L223 and L225 and can be exported from the nucleus in a CRM1-dependent manner. PMID:26429201

  14. Converting the ISS to an Earth-Moon Transport System Using Nuclear Thermal Propulsion

    NASA Astrophysics Data System (ADS)

    Paniagua, John; Maise, George; Powell, James

    2008-01-01

    Using Nuclear Thermal Propulsion (NTP), the International Space Station (ISS) can be placed into a cyclic orbit between the Earth and the Moon for 2-way transport of personnel and supplies to a permanent Moon Base. The ISS cycler orbit apogees 470,000 km from Earth, with a period of 13.66 days. Once a month, the ISS would pass close to the Moon, enabling 2-way transport between it and the surface using a lunar shuttle craft. The lunar shuttle craft would land at a desired location on the surface during a flyby and return to the ISS during a later flyby. At Earth perigee 7 days later at 500 km altitude, there would be 2-way transport between it and Earth's surface using an Earth shuttle craft. The docking Earth shuttle would remain attached to the ISS as it traveled towards the Moon, while personnel and supplies transferred to a lunar shuttle spacecraft that would detach and land at the lunar base when the ISS swung around the Moon. The reverse process would be carried out to return personnel and materials from the Moon to the Earth. The orbital mechanics for the ISS cycle are described in detail. Based on the full-up mass of 400 metric tons for the ISS, an ISP of 900 seconds, and a delta V burn of 3.3 km/sec to establish the orbit, 200 metric tons of liquid H-2 propellant would be required. The 200 metric tons could be stored in 3 tanks, each 8 meters in diameter and 20 meters in length. An assembly of 3 MITEE NTP engines would be used, providing redundancy if an engine were to fail. Two different MITEE design options are described. Option 1 is an 18,000 Newton, 100 MW engine with a thrust to weight ratio of 6.6/1 Option 2 is a 180,000 Newton, 1000 MW engine with a thrust to weight ratio of 23/1. Burn times to establish the orbit are ~1 hour for the large 3 engine assembly, and 10 hours for the small 3 engine assembly. Both engines would use W-UO2 cermet fuel at ~2750 K which has demonstrated the capability to operate for at least 50 hours in 2750 K hydrogen with

  15. Converting the ISS to an Earth-Moon Transport System Using Nuclear Thermal Propulsion

    SciTech Connect

    Paniagua, John; Maise, George; Powell, James

    2008-01-21

    Using Nuclear Thermal Propulsion (NTP), the International Space Station (ISS) can be placed into a cyclic orbit between the Earth and the Moon for 2-way transport of personnel and supplies to a permanent Moon Base. The ISS cycler orbit apogees 470,000 km from Earth, with a period of 13.66 days. Once a month, the ISS would pass close to the Moon, enabling 2-way transport between it and the surface using a lunar shuttle craft. The lunar shuttle craft would land at a desired location on the surface during a flyby and return to the ISS during a later flyby. At Earth perigee 7 days later at 500 km altitude, there would be 2-way transport between it and Earth's surface using an Earth shuttle craft. The docking Earth shuttle would remain attached to the ISS as it traveled towards the Moon, while personnel and supplies transferred to a lunar shuttle spacecraft that would detach and land at the lunar base when the ISS swung around the Moon. The reverse process would be carried out to return personnel and materials from the Moon to the Earth. The orbital mechanics for the ISS cycle are described in detail. Based on the full-up mass of 400 metric tons for the ISS, an ISP of 900 seconds, and a delta V burn of 3.3 km/sec to establish the orbit, 200 metric tons of liquid H-2 propellant would be required. The 200 metric tons could be stored in 3 tanks, each 8 meters in diameter and 20 meters in length. An assembly of 3 MITEE NTP engines would be used, providing redundancy if an engine were to fail. Two different MITEE design options are described. Option 1 is an 18,000 Newton, 100 MW engine with a thrust to weight ratio of 6.6/1; Option 2 is a 180,000 Newton, 1000 MW engine with a thrust to weight ratio of 23/1. Burn times to establish the orbit are {approx}1 hour for the large 3 engine assembly, and 10 hours for the small 3 engine assembly. Both engines would use W-UO2 cermet fuel at {approx}2750 K which has demonstrated the capability to operate for at least 50 hours in 2750 K

  16. Effect of transport-pathway simplifications on projected releases of radionuclides from a nuclear waste repository (Sweden)

    NASA Astrophysics Data System (ADS)

    Selroos, Jan-Olof; Painter, Scott L.

    2012-12-01

    The Swedish Nuclear Fuel and Waste Management Company has recently submitted an application for a license to construct a final repository for spent nuclear fuel, at approximately 500 m depth in crystalline bedrock. Migration pathways through the geosphere barrier are geometrically complex, with segments in fractured rock, deformation zones, backfilled tunnels, and near-surface soils. Several simplifications of these complex migration pathways were used in the assessments of repository performance that supported the license application. Specifically, in the geosphere transport calculations, radionuclide transport in soils and tunnels was neglected, and deformation zones were assumed to have transport characteristics of fractured rock. The effects of these simplifications on the projected performance of the geosphere barrier system are addressed. Geosphere performance is shown to be sensitive to how transport characteristics of deformation zones are conceptualized and incorporated into the model. Incorporation of advective groundwater travel time within backfilled tunnels reduces radiological dose from non-sorbing radionuclides such as I-129, while sorption in near-surface soils reduces radiological doses from sorbing radionuclides such as Ra-226. These results help quantify the degree to which geosphere performance was pessimistically assessed, and provide some guidance on how future studies to reduce uncertainty in geosphere performance may be focused.

  17. Daily variation of constitutively activated nuclear factor kappa B (NFKB) in rat pineal gland.

    PubMed

    Cecon, Erika; Fernandes, Pedro A; Pinato, Luciana; Ferreira, Zulma S; Markus, Regina P

    2010-01-01

    In mammals, the production of melatonin by the pineal gland is mainly controlled by the suprachiasmatic nuclei (SCN), the master clock of the circadian system. We have previously shown that agents involved in inflammatory responses, such as cytokines and corticosterone, modulate pineal melatonin synthesis. The nuclear transcription factor NFKB, detected by our group in the rat pineal gland, modulates this effect. Here, we evaluated a putative constitutive role for the pineal gland NFKB pathway. Male rats were kept under 12 h:12 h light-dark (LD) cycle or under constant darkness (DD) condition. Nuclear NFKB was quantified by electrophoretic mobility shift assay on pineal glands obtained from animals killed throughout the day at different times. Nuclear content of NFKB presented a daily rhythm only in LD-entrained animals. During the light phase, the amount of NFKB increased continuously, and a sharp drop occurred when lights were turned off. Animals maintained in a constant light environment until ZT 18 showed diurnal levels of nuclear NFKB at ZT15 and ZT18. Propranolol (20 mg/kg, i.p., ZT 11) treatment, which inhibits nocturnal sympathetic input, impaired nocturnal decrease of NFKB only at ZT18. A similar effect was observed in free-running animals, which secreted less nocturnal melatonin. Because melatonin reduces constitutive NFKB activation in cultured pineal glands, we propose that this indolamine regulates this transcription factor pathway in the rat pineal gland, but not at the LD transition. The controversial results regarding the inhibition of pineal function by constant light or blocking sympathetic neurotransmission are discussed according to the hypothesis that the prompt effect of lights-off is not mediated by noradrenaline, which otherwise contributes to maintaining low levels of nuclear NFKB at night. In summary, we report here a novel transcription factor in the pineal gland, which exhibits a constitutive rhythm dependent on environmental photic

  18. Viral and Cellular Factors Involved in Phloem Transport of Plant Viruses

    PubMed Central

    Hipper, Clémence; Brault, Véronique; Ziegler-Graff, Véronique; Revers, Frédéric

    2013-01-01

    Phloem transport of plant viruses is an essential step in the setting-up of a complete infection of a host plant. After an initial replication step in the first cells, viruses spread from cell-to-cell through mesophyll cells, until they reach the vasculature where they rapidly move to distant sites in order to establish the infection of the whole plant. This last step is referred to as systemic transport, or long-distance movement, and involves virus crossings through several cellular barriers: bundle sheath, vascular parenchyma, and companion cells for virus loading into sieve elements (SE). Viruses are then passively transported within the source-to-sink flow of photoassimilates and are unloaded from SE into sink tissues. However, the molecular mechanisms governing virus long-distance movement are far from being understood. While most viruses seem to move systemically as virus particles, some viruses are transported in SE as viral ribonucleoprotein complexes (RNP). The nature of the cellular and viral factors constituting these RNPs is still poorly known. The topic of this review will mainly focus on the host and viral factors that facilitate or restrict virus long-distance movement. PMID:23745125

  19. Viral and cellular factors involved in Phloem transport of plant viruses.

    PubMed

    Hipper, Clémence; Brault, Véronique; Ziegler-Graff, Véronique; Revers, Frédéric

    2013-01-01

    Phloem transport of plant viruses is an essential step in the setting-up of a complete infection of a host plant. After an initial replication step in the first cells, viruses spread from cell-to-cell through mesophyll cells, until they reach the vasculature where they rapidly move to distant sites in order to establish the infection of the whole plant. This last step is referred to as systemic transport, or long-distance movement, and involves virus crossings through several cellular barriers: bundle sheath, vascular parenchyma, and companion cells for virus loading into sieve elements (SE). Viruses are then passively transported within the source-to-sink flow of photoassimilates and are unloaded from SE into sink tissues. However, the molecular mechanisms governing virus long-distance movement are far from being understood. While most viruses seem to move systemically as virus particles, some viruses are transported in SE as viral ribonucleoprotein complexes (RNP). The nature of the cellular and viral factors constituting these RNPs is still poorly known. The topic of this review will mainly focus on the host and viral factors that facilitate or restrict virus long-distance movement. PMID:23745125

  20. mReg2 inhibits nuclear entry of apoptosis-inducing factor in mouse insulinoma cells.

    PubMed

    Liu, Lu; Chowdhury, Subrata; Uppal, Sadaf; Fang, Xin; Liu, Jun-Li; Srikant, Coimbatore B

    2015-02-01

    We have reported earlier that murine-regenerating gene mReg2 protects MIN6 mouse insulinoma cells from ER stress and caspase-mediated apoptosis. In apoptotic cells, DNA damage is induced by the nuclear translocation of mitochondrial apoptosis-inducing factor (AIF). Here we tested the hypothesis that mReg2 may regulate Scythe and/or hsp70 which influence the nuclear import of AIF. Treatment with thapsigargin (Tg) or doxorubicin induced an increase in nuclear AIF in MIN6 cells carrying the empty transfection vector (MIN6-VC) but not in cells overexpressing mReg2 (MIN6-mReg2). On one hand, nuclear Scythe was higher in the nucleus of MIN6-mReg2 compared with that in MIN6-VC cells. mReg2 did not alter the expression of AIF or Scythe. On the other hand, mReg2 induced the expression of hsp70 which is known to promote cytosolic retention of AIF. We conclude that mReg2 inhibits AIF-mediated apoptosis by promoting the nuclear presence of Scythe and inducing hsp70.

  1. Using full-mission simulation for human factors research in air transport operations

    NASA Technical Reports Server (NTRS)

    Orlady, Harry W.; Hennessy, Robert W.; Obermayer, Richard; Vreuls, Donald; Murphy, Miles R.

    1988-01-01

    This study examined state-of-the-art mission oriented simulation and its use in human factors research. Guidelines were developed for doing full-mission human factors research on crew member behavior during simulated air transport operations. The existing literature was reviewed. However, interviews with experienced investigators provided the most useful information. The fundamental scientific and practical issues of behavioral research in a simulation environment are discussed. Guidelines are presented for planning, scenario development, and the execution of behavioral research using full-mission simulation in the context of air transport flight operations . Research is recommended to enhance the validity and productivity of full-mission research by: (1) validating the need for high-fidelity simulation of all major elements in the operational environment, (2) improving methods for conducting full-mission research, and (3) examining part-task research on specific problems through the use of vehicles which contain higher levels of abstraction (and lower fidelity) of the operational environment.

  2. Nuclear Localization of the Mitochondrial Factor HIGD1A during Metabolic Stress

    PubMed Central

    Ameri, Kurosh; Rajah, Anthony M.; Nguyen, Vien; Sanders, Timothy A.; Jahangiri, Arman; DeLay, Michael; Donne, Matthew; Choi, Hwa J.; Tormos, Kathryn V.; Yeghiazarians, Yerem; Jeffrey, Stefanie S.; Rinaudo, Paolo F.; Rowitch, David H.; Aghi, Manish; Maltepe, Emin

    2013-01-01

    Cellular stress responses are frequently governed by the subcellular localization of critical effector proteins. Apoptosis-inducing Factor (AIF) or Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), for example, can translocate from mitochondria to the nucleus, where they modulate apoptotic death pathways. Hypoxia-inducible gene domain 1A (HIGD1A) is a mitochondrial protein regulated by Hypoxia-inducible Factor-1α (HIF1α). Here we show that while HIGD1A resides in mitochondria during physiological hypoxia, severe metabolic stress, such as glucose starvation coupled with hypoxia, in addition to DNA damage induced by etoposide, triggers its nuclear accumulation. We show that nuclear localization of HIGD1A overlaps with that of AIF, and is dependent on the presence of BAX and BAK. Furthermore, we show that AIF and HIGD1A physically interact. Additionally, we demonstrate that nuclear HIGD1A is a potential marker of metabolic stress in vivo, frequently observed in diverse pathological states such as myocardial infarction, hypoxic-ischemic encephalopathy (HIE), and different types of cancer. In summary, we demonstrate a novel nuclear localization of HIGD1A that is commonly observed in human disease processes in vivo. PMID:23646141

  3. p115 is a general vesicular transport factor related to the yeast endoplasmic reticulum to Golgi transport factor Uso1p.

    PubMed Central

    Sapperstein, S K; Walter, D M; Grosvenor, A R; Heuser, J E; Waters, M G

    1995-01-01

    A recently discovered vesicular transport factor, termed p115, is required along with N-ethylmaleimide-sensitive fusion protein (NSF) and soluble NSF attachment proteins for in vitro Golgi transport. p115 is a peripheral membrane protein found predominantly on the Golgi. Biochemical and electron microscopic analyses indicate that p115 is an elongated homodimer with two globular "heads" and an extended "tail" reminiscent of myosin II. We have cloned and sequenced cDNAs for bovine and rat p115. The predicted translation products are 90% identical, and each can be divided into three domains. The predicted 108-kDa bovine protein consists of an N-terminal 73-kDa globular domain followed by a 29-kDa coiled-coil dimerization domain, a linker segment of 4 kDa, and a highly acidic domain of 3 kDa. p115 is related to Uso1p, a protein required for endoplasmic reticulum to Golgi vesicular transport in Saccharomyces cerevisiae, which has a similar "head-coil-acid" domain structure. The p115 and Uso1p heads are similar in size, have approximately 25% sequence identity, and possess two highly homologous regions (62% and 60% identity over 34 and 53 residues, respectively). There is a third region of homology (50% identity over 28 residues) between the coiled-coil and acidic domains. Although the acidic nature of the p115 and Uso1p C termini is conserved, the primary sequence is not. We discuss these results in light of the proposed function of p115 in membrane targeting and/or fusion. Images Fig. 1 Fig. 3 PMID:7831323

  4. Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes.

    PubMed

    Wu, Shan; Tutuncuoglu, Beril; Yan, Kaige; Brown, Hailey; Zhang, Yixiao; Tan, Dan; Gamalinda, Michael; Yuan, Yi; Li, Zhifei; Jakovljevic, Jelena; Ma, Chengying; Lei, Jianlin; Dong, Meng-Qiu; Woolford, John L; Gao, Ning

    2016-05-25

    Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm. Hundreds of assembly factors, organized into sequential functional groups, facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo-electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly.

  5. Diverse roles of assembly factors revealed by structures of late nuclear pre-60S ribosomes.

    PubMed

    Wu, Shan; Tutuncuoglu, Beril; Yan, Kaige; Brown, Hailey; Zhang, Yixiao; Tan, Dan; Gamalinda, Michael; Yuan, Yi; Li, Zhifei; Jakovljevic, Jelena; Ma, Chengying; Lei, Jianlin; Dong, Meng-Qiu; Woolford, John L; Gao, Ning

    2016-06-01

    Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and ribosomal RNA remodelling events in the nucleolus, nucleoplasm and cytoplasm. Hundreds of assembly factors, organized into sequential functional groups, facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these assembly factors function are largely unknown. Here we use cryo-electron microscopy to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged assembly factor Nog2. Our data pinpoint the locations and determine the structures of over 20 assembly factors, which are enriched in two areas: an arc region extending from the central protuberance to the polypeptide tunnel exit, and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S ribosomal RNAs. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant assembly factors and functional ribosomal RNA elements, manifesting their critical roles in structural remodelling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodelling events before nuclear export: rotation of the 5S ribonucleoprotein, construction of the active centre and ITS2 removal. The rich structural information in our structures provides a framework to dissect molecular roles of diverse assembly factors in eukaryotic ribosome assembly. PMID:27251291

  6. Pyridoxamine is a substrate of the energy-coupling factor transporter HmpT

    PubMed Central

    Wang, Tingliang; de Jesus, Armando Jerome; Shi, Yigong; Yin, Hang

    2015-01-01

    Energy-coupling factor (ECF) transporters belong to a novel family of proteins that forms a subset within the ATP-binding cassette (ABC) transporter family. These proteins are responsible for the uptake of micronutrients in bacteria. ECF transporters are composed of four proteins: the A- and A′-components, the T-component and the S-component. One of the ECF transporters, named HmpT, was crystallized in the apo form with all four components. It is currently unknown whether HmpT serves as a transporter for hydroxymethyl pyrimidine or the different forms of vitamin B6 (pyridoxine, pyridoxal or pyridoxamine). Using a combination of molecular dynamics (MD) simulations and mass spectrometry, we have identified pyridoxamine to be the preferred substrate of HmpT. Mass spectra show that the mass of the substrate from the HmpT–substrate complex matches that of pyridoxamine. MD simulations likewise indicate that pyridoxamine interacts most strongly with most of the conserved residues of the S-component (Glu 41, His 84 and Gln 43) compared with the other vitamin B6 forms. Furthermore, the simulations have implied that loops 1 and 5 of the S-component can participate in the gating action for HmpT. PMID:27462413

  7. Influencing factors on particle-bound contaminant transport in the Elbe estuary

    NASA Astrophysics Data System (ADS)

    Kleisinger, Carmen; Haase, Holger; Schubert, Birgit

    2016-04-01

    Particulate matter, i.e. suspended particulate matter and sediments in rivers and estuaries, often are contaminated with trace metals and selected organic contaminants and are mainly associated with fine-grained fractions. Transport processes and fate of particles in estuaries are influenced by several factors, e.g. freshwater discharge, tide, flow velocity and dredging activities (Kappenberg et al., 2007). Understanding the transport processes in estuaries may help to achieve the objectives of the Water Framework Directive and the Marine Strategy Framework Directive. The German Federal Institute of Hydrology (BfG) operates for more than 20 years five monitoring sites in the Elbe estuary in order to monitor the development of particle-bound contaminant concentrations over time and to understand their transport mechanisms. Results of the monitoring revealed freshwater discharge as an important influencing factor on the transport of contaminated particulate matter (Ackermann et al., 2007). The bidirectional transport of marine and fluvial water and particulate matter in estuaries results in a turbidity zone where large amounts of particulate matter are temporarily retained and thus in a delayed transport of particulate matter towards the sea. The extent and the location of the turbidity zone as well as the ratio of highly contaminated fluvial and less contaminated marine sediments at a given location are mainly influenced by the freshwater discharge (Kowalewska et al., 2011). Furthermore, at high freshwater discharge conditions the highly contaminated particulate matter from fluvial origin are transported downstream the estuary, whereas at low freshwater discharges, upstream transport of less contaminated marine sediments prevails. Hence, residence times of particulate matter in the estuary are difficult to estimate. Furthermore, sedimentation areas with flow reduced conditions, e.g. wadden areas or branches of the Elbe estuary, may act as sinks for particle bound

  8. LETTER: Construction of the factorized steady state distribution in models of mass transport

    NASA Astrophysics Data System (ADS)

    Zia, R. K. P.; Evans, M. R.; Majumdar, Satya N.

    2004-10-01

    For a class of one-dimensional mass transport models we present a simple and direct test on the chipping functions, which define the probabilities for mass to be transferred to neighbouring sites, to determine whether the stationary distribution is factorized. In cases where the answer is affirmative, we provide an explicit method for constructing the single-site weight function. As an illustration of the power of this approach, previously known results on the zero-range process and asymmetric random average process are recovered in a few lines. We also construct new models, namely a generalized zero-range process and a binomial chipping model, which have factorized steady states.

  9. Proteins that mediate the nuclear entry of the goat uterine estrogen receptor activation factor (E-RAF): identification of a molecular basis for the inhibitory effect of progesterone on estrogen action.

    PubMed

    Govind, Anitha P; Sreeja, S; Thampan, Raghava Varman

    2003-05-01

    A 66 kDa transport protein, tp66, has been identified as the protein that mediates the nuclear transport of the estrogen receptor activation factor (E-RAF). Indirect evidence shows that tp66 influences the transport of E-RAF mainly by recognizing the nuclear localization signals (NLS) on the latter. A 38 kDa nuclear pore complex protein (npcp38) has been identified to which tp66-E-RAF complex gets 'docked' prior to the nuclear entry of E-RAF. Progesterone binding to E-RAF serves to dissociate E-RAF from the tp66 thereby inhibiting the nuclear entry of E-RAF. The demonstration of the high affinity progesterone binding property of E-RAF adds credibility to the above findings. A change in conformation of E-RAF being brought about by progesterone binding is evident from the results of the circular dichroism (CD) analysis. This appears to be the fundamental reason behind the dissociation of the tp66-E-RAF complex under progesterone influence and provides a molecular basis for the estrogen 'antagonistic' action of progesterone. A nuclear run-on transcription assay clearly demonstrates the transcription-activation function of E-RAF II, also reaffirming the functional role of tp66 in the nuclear entry of E-RAF. PMID:12682912

  10. Generation of Bondarenko F factors with MCNP5 for use in scale transport codes

    SciTech Connect

    Hart, S.; Maldonado, G. I.

    2012-07-01

    Generally there are three methods of cross-section processing available when using the Scale computer code. They are NITAWL, BONAMI, and CENTRM, with CENTRM being the most common and accurate, but computationally expensive. In order to improve the accuracy of BONAMI (which uses the Bondarenko Method), new Bondarenko/F Factors were to be generated that will smooth out the current F Factors that are being generated using CENTRM. The case discussed here involves using a dedicated Monte Carlo code (MCNP5) to calculate the transport solution from which shielded cross-sections can be produced directly for the transport geometry/mesh. A simple program was created to parse and collect the tallied cross-sections from the MCNP output, which was fed into a modified CLAROL input (a module that replaces or adds data in an AMPX master library), which used the cross-sections obtained from MCNP to calculate new F-factors and update the SCALE library. This approach allows the use of other methods to generate the shielded cross-sections and for easy comparison to existing results. Initial proof-of-principle calculations were carried out for an various cases using various transport solvers, such as NEWT, KENO, and XSDRN, with BONAMI in SCALE. Poor results were obtained using cross-sections generated using infinite homogeneous cases, but good results were obtained by using pin cells in an infinite lattice. (authors)

  11. Report on interim storage of spent nuclear fuel. Midwestern high-level radioactive waste transportation project

    SciTech Connect

    Not Available

    1993-04-01

    The report on interim storage of spent nuclear fuel discusses the technical, regulatory, and economic aspects of spent-fuel storage at nuclear reactors. The report is intended to provide legislators state officials and citizens in the Midwest with information on spent-fuel inventories, current and projected additional storage requirements, licensing, storage technologies, and actions taken by various utilities in the Midwest to augment their capacity to store spent nuclear fuel on site.

  12. Importin β1 mediates nuclear factor-κB signal transduction into the nuclei of myeloma cells and affects their proliferation and apoptosis.

    PubMed

    Yan, Wenqing; Li, Rong; He, Jie; Du, Juan; Hou, Jian

    2015-04-01

    Multiple myeloma (MM) is a plasma cell neoplasm that is currently incurable. The activation of nuclear factor-κB (NF-κB) signalling plays a crucial role in the immortalisation of MM cells. As the most important transcription factor of the canonical NF-κB pathway, the p50/p65 heterodimer requires transportation into the nucleus for its successful signal transduction. Importin β1 is the key transport receptor that mediates p50/p65 nuclear import. Currently, it remains unclear whether the regulation of importin β1 function affects the biological behaviour of MM cells. In the present study, we investigated the changes in p65 translocation and the proliferation and apoptosis of MM cells after treatment with small interfering RNA (siRNA) or an importin β1 inhibitor. The underlying mechanisms were also investigated. We found importin β1 over-expression and the excessive nuclear transport of p65 in myeloma cells. Confocal laser scanning microscopy and Western blot analysis results indicated that p65 nuclear transport was blocked after inhibiting importin β1 expression with siRNA and the importin β1-specific inhibitor importazole (IPZ). Importantly, electronic mobility shift assay results also verified that p65 nuclear transport was dramatically reduced. Moreover, the expression of the NF-κB signalling target genes involved in MM cell apoptosis, such as BCL-2, c-IAP1 and XIAP, were markedly reduced, as demonstrated by the RT-PCR results. Furthermore, the proliferation of MM cells was inhibited, as demonstrated by MTT assay results, and the MM cell apoptosis rate was higher, as demonstrated by the annexin V/propidium iodide (PI) double-staining assay results. Additionally, the percentage of S phase cells in the myeloma cell lines treated with IPZ was dramatically reduced. In conclusion, our results clearly show that importin β1 mediates the translocation of NF-κB into the nuclei of myeloma cells, thereby regulating proliferation and blocking apoptosis, which

  13. Stress-induced nuclear bodies are sites of accumulation of pre-mRNA processing factors.

    PubMed

    Denegri, M; Chiodi, I; Corioni, M; Cobianchi, F; Riva, S; Biamonti, G

    2001-11-01

    Heterogeneous nuclear ribonucleoprotein (hnRNP) HAP (hnRNP A1 interacting protein) is a multifunctional protein with roles in RNA metabolism, transcription, and nuclear structure. After stress treatments, HAP is recruited to a small number of nuclear bodies, usually adjacent to the nucleoli, which consist of clusters of perichromatin granules and are depots of transcripts synthesized before stress. In this article we show that HAP bodies are sites of accumulation for a subset of RNA processing factors and are related to Sam68 nuclear bodies (SNBs) detectable in unstressed cells. Indeed, HAP and Sam68 are both present in SNBs and in HAP bodies, that we rename "stress-induced SNBs." The determinants required for the redistribution of HAP lie between residue 580 and 788. Different portions of this region direct the recruitment of the green fluorescent protein to stress-induced SNBs, suggesting an interaction of HAP with different components of the bodies. With the use of the 580-725 region as bait in a two-hybrid screening, we have selected SRp30c and 9G8, two members of the SR family of splicing factors. Splicing factors are differentially affected by heat shock: SRp30c and SF2/ASF are efficiently recruited to stress-induced SNBs, whereas the distribution of SC35 is not perturbed. We propose that the differential sequestration of splicing factors could affect processing of specific transcripts. Accordingly, the formation of stress-induced SNBs is accompanied by a change in the splicing pattern of the adenovirus E1A transcripts.

  14. [Prenosologic criteria of health disorders and cardiovascular risk factors in workers engaged into nuclear industry].

    PubMed

    Shpagina, L A; Vorob'ev, V A; Smirnova, I N; Panacheva, L A; Drobyshev, V A; Abramovich, S G; Titskaya, E V; Reshetova, G G; Tonkoshkurova, A V; Saraskina, L E

    2016-01-01

    Prophylactic study among workers engaged into main production of Siberian chemical enterprise (Seversk city) revealed high frequency of cardiovascular risk factors (overweight, hypodynamia, dyslipidemia, arterial hypertension), low level of adaptational potential and integral somatic health parameter as prenosologic criteria of cardiovascular diseases. The results necessitate recommendations to supplement periodic medical examinations with studies aimed to reveal early criteria of health disorders, and determine priority directions to specify prophylactic measures in nuclear industry workers. PMID:27164750

  15. [Prenosologic criteria of health disorders and cardiovascular risk factors in workers engaged into nuclear industry].

    PubMed

    Shpagina, L A; Vorob'ev, V A; Smirnova, I N; Panacheva, L A; Drobyshev, V A; Abramovich, S G; Titskaya, E V; Reshetova, G G; Tonkoshkurova, A V; Saraskina, L E

    2016-01-01

    Prophylactic study among workers engaged into main production of Siberian chemical enterprise (Seversk city) revealed high frequency of cardiovascular risk factors (overweight, hypodynamia, dyslipidemia, arterial hypertension), low level of adaptational potential and integral somatic health parameter as prenosologic criteria of cardiovascular diseases. The results necessitate recommendations to supplement periodic medical examinations with studies aimed to reveal early criteria of health disorders, and determine priority directions to specify prophylactic measures in nuclear industry workers.

  16. Characterization of Inhibitors of Glucocorticoid Receptor Nuclear Translocation: A Model of Cytoplasmic Dynein-Mediated Cargo Transport

    PubMed Central

    Daghestani, Hikmat N.; Zhu, Guangyu; Shinde, Sunita N.; Brodsky, Jeffrey L.

    2012-01-01

    Abstract Agonist-induced glucocorticoid receptor [GR] transport from the cytoplasm to the nucleus was used as a model to identify dynein-mediated cargo transport inhibitors. Cell-based screening of the library of pharmacologically active compound (LOPAC)-1280 collection identified several small molecules that stalled the agonist-induced transport of GR-green fluorescent protein (GFP) in a concentration-dependent manner. Fluorescent images of microtubule organization, nuclear DNA staining, expression of GR-GFP, and its subcellular distribution were inspected and quantified by image analysis to evaluate the impact of compounds on cell morphology, toxicity, and GR transport. Given the complexity of the multi-protein complex involved in dynein-mediated cargo transport and the variety of potential mechanisms for interruption of that process, we therefore developed and validated a panel of biochemical assays to investigate some of the more likely intracellular target(s) of the GR transport inhibitors. Although the apomorphine enantiomers exhibited the most potency toward the ATPase activities of cytoplasmic dynein, myosin, and the heat-shock proteins (HSPs), their apparent lack of specificity made them unattractive for further study in our quest. Other molecules appeared to be nonspecific inhibitors that targeted reactive cysteines of proteins. Ideally, specific retrograde transport inhibitors would either target dynein itself or one of the other important proteins associated with the transport process. Although the hits from the cell-based screen of the LOPAC-1280 collection did not exhibit this desired profile, this screening platform provided a promising phenotypic system for the discovery of dynein/HSP modulators. PMID:21919741

  17. Transportation.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with transportation and energy use. Its objective is for the student to be able to discuss the implication of energy usage as it applies to the area of transportation. Some topics covered are efficiencies of various transportation…

  18. Stakeholder Transportation Scorecard: Reviewing Nevada's Recommendations for Enhancing the Safety and Security of Nuclear Waste Shipments - 13518

    SciTech Connect

    Dilger, Fred C.; Ballard, James D.; Halstead, Robert J.

    2013-07-01

    As a primary stakeholder in the Yucca Mountain program, the state of Nevada has spent three decades examining and considering national policy regarding spent nuclear fuel and high-level radioactive waste transportation. During this time, Nevada has identified 10 issues it believes are critical to ensuring the safety and security of any spent nuclear fuel transportation program, and achieving public acceptance. These recommendations are: 1) Ship the oldest fuel first; 2) Ship mostly by rail; 3) Use dual-purpose (transportable storage) casks; 4) Use dedicated trains for rail shipments; 5) Implement a full-scale cask testing program; 6) Utilize a National Environmental Policy Act (NEPA) process for the selection of a new rail spur to the proposed repository site; 7) Implement the Western Interstate Energy Board (WIEB) 'straw man' process for route selection; 8) Implement Section 180C assistance to affected States, Tribes and localities through rulemaking; 9) Adopt safety and security regulatory enhancements proposed states; and 10) Address stakeholder concerns about terrorism and sabotage. This paper describes Nevada's proposals in detail and examines their current status. The paper describes the various forums and methods by which Nevada has presented its arguments and sought to influence national policy. As of 2012, most of Nevada's recommendations have been adopted in one form or another, although not yet implemented. If implemented in a future nuclear waste program, the State of Nevada believes these recommendations would form the basis for a successful national transportation plan for shipments to a geologic repository and/or centralized interim storage facility. (authors)

  19. Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression.

    PubMed

    Donepudi, Ajay C; Cheng, Qiuqiong; Lu, Zhenqiang James; Cherrington, Nathan J; Slitt, Angela L

    2016-04-01

    Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor- and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. PMID:26847773

  20. Nuclear factor kappaB/p49 is a negative regulatory factor in nerve growth factor-induced choline acetyltransferase promoter activity in PC12 cells.

    PubMed

    Toliver-Kinsky, T; Wood, T; Perez-Polo, J R

    2000-12-01

    Anovel nuclear factor kappaB (NF-kappaB) binding site has been identified within the promoter region of the mouse gene encoding choline acetyltransferase (ChAT), the enzyme that synthesizes acetylcholine and has been implicated in the cognitive deficits associated with aging and Alzheimer's disease. This binding site, which is located within the nerve growth factor (NGF)-responsive enhancer element, was recognized by the NF-kappaB protein p49 but not p65 or p50. p49 from both basal forebrain and PC12 nuclear extracts interacted with this specific sequence in electrophoretic mobility shift assays. Mutation of the NF-kappaB site caused an increase in NGF-induced promoter activation, whereas overexpression of p49 in NGF-differentiated PC12 cells caused a decrease in endogenous ChAT enzyme activity and a decrease in promoter activity that was specifically mediated through this NF-kappaB binding site. Treatment of PC12 cells with NGF resulted in a drastic reduction in nuclear p49 binding to the ChAT NF-kappaB site after 24 h, but nuclear p49 levels were not altered, suggesting that late NGF-mediated events prevent binding of p49 to the ChAT promoter by an unknown mechanism other than nuclear translocation. Decreased ChAT expression and increased NF-kappaB activity in the brain are associated with aging and Alzheimer's disease. These data indicate that p49 is a negative regulator of ChAT expression and suggest a possible mechanism for aging-associated declines in cholinergic function.

  1. Transcription Factor Hepatocyte Nuclear Factor-1β Regulates Renal Cholesterol Metabolism.

    PubMed

    Aboudehen, Karam; Kim, Min Soo; Mitsche, Matthew; Garland, Kristina; Anderson, Norma; Noureddine, Lama; Pontoglio, Marco; Patel, Vishal; Xie, Yang; DeBose-Boyd, Russell; Igarashi, Peter

    2016-08-01

    HNF-1β is a tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β-regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin-like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism. PMID:26712526

  2. 10 CFR Appendix E to Part 73 - Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1 E Appendix E to Part 73 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Pt. 73, App. E Appendix E to Part 73—Levels...

  3. 10 CFR Appendix E to Part 73 - Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 2 2012-01-01 2012-01-01 false Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1 E Appendix E to Part 73 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Pt. 73, App. E Appendix E to Part 73—Levels...

  4. 10 CFR Appendix E to Part 73 - Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1 E Appendix E to Part 73 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Pt. 73, App. E Appendix E to Part 73—Levels...

  5. 10 CFR Appendix E to Part 73 - Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1 E Appendix E to Part 73 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Pt. 73, App. E Appendix E to Part 73—Levels...

  6. 10 CFR Appendix E to Part 73 - Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Levels of Physical Protection To Be Applied in International Transport of Nuclear Material 1 E Appendix E to Part 73 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) PHYSICAL PROTECTION OF PLANTS AND MATERIALS Pt. 73, App. E Appendix E to Part 73—Levels...

  7. Transcription factors nuclear factor I and Sp1 interact with the murine collagen alpha 1 (I) promoter.

    PubMed Central

    Nehls, M C; Rippe, R A; Veloz, L; Brenner, D A

    1991-01-01

    The collagen alpha 1(I) promoter, which is efficiently transcribed in NIH 3T3 fibroblasts, contains four binding sites for trans-acting factors, as demonstrated by DNase I protection assays (D. A. Brenner, R. A. Rippe, and L. Veloz, Nucleic Acids Res. 17:6055-6064, 1989). This study characterizes the DNA-binding proteins that interact with the two proximal footprinted regions, both of which contain a reverse CCAAT box and a G + C-rich 12-bp direct repeat. Analysis by DNase I protection assays, mobility shift assays, competition with specific oligonucleotides, binding with recombinant proteins, and reactions with specific antisera showed that the transcriptional factors nuclear factor I (NF-I) and Sp1 bind to these two footprinted regions. Because of overlapping binding sites, NF-I binding and Sp1 binding appear to be mutually exclusive. Overexpression of NF-I in cotransfection experiments with the alpha 1(I) promoter in NIH 3T3 fibroblasts increased alpha 1(I) expression, while Sp1 overexpression reduced this effect, as well as basal promoter activity. The herpes simplex virus thymidine kinase promoter, which contains independent NF-I- and Sp1-binding sites, was stimulated by both factors. Therefore, expression of the collagen alpha 1(I) gene may depend on the relative activities of NF-I and Sp1. Images PMID:2072909

  8. The "RTR" medical response system for nuclear and radiological mass-casualty incidents: a functional TRiage-TReatment-TRansport medical response model.

    PubMed

    Hrdina, Chad M; Coleman, C Norman; Bogucki, Sandy; Bader, Judith L; Hayhurst, Robert E; Forsha, Joseph D; Marcozzi, David; Yeskey, Kevin; Knebel, Ann R

    2009-01-01

    Developing a mass-casualty medical response to the detonation of an improvised nuclear device (IND) or large radiological dispersal device (RDD) requires unique advanced planning due to the potential magnitude of the event, lack of warning, and radiation hazards. In order for medical care and resources to be collocated and matched to the requirements, a [US] Federal interagency medical response-planning group has developed a conceptual approach for responding to such nuclear and radiological incidents. The "RTR" system (comprising Radiation-specific TRiage, TReatment, TRansport sites) is designed to support medical care following a nuclear incident. Its purpose is to characterize, organize, and efficiently deploy appropriate materiel and personnel assets as close as physically possible to various categories of victims while preserving the safety of responders. The RTR system is not a medical triage system for individual patients. After an incident is characterized and safe perimeters are established, RTR sites should be determined in real-time that are based on the extent of destruction, environmental factors, residual radiation, available infrastructure, and transportation routes. Such RTR sites are divided into three types depending on their physical/situational relationship to the incident. The RTR1 sites are near the epicenter with residual radiation and include victims with blast injuries and other major traumatic injuries including radiation exposure; RTR2 sites are situated in relationship to the plume with varying amounts of residual radiation present, with most victims being ambulatory; and RTR3 sites are collection and transport sites with minimal or no radiation present or exposure risk and a victim population with a potential variety of injuries or radiation exposures. Medical Care sites are predetermined sites at which definitive medical care is given to those in immediate need of care. They include local/regional hospitals, medical centers, other

  9. The "RTR" medical response system for nuclear and radiological mass-casualty incidents: a functional TRiage-TReatment-TRansport medical response model.

    PubMed

    Hrdina, Chad M; Coleman, C Norman; Bogucki, Sandy; Bader, Judith L; Hayhurst, Robert E; Forsha, Joseph D; Marcozzi, David; Yeskey, Kevin; Knebel, Ann R

    2009-01-01

    Developing a mass-casualty medical response to the detonation of an improvised nuclear device (IND) or large radiological dispersal device (RDD) requires unique advanced planning due to the potential magnitude of the event, lack of warning, and radiation hazards. In order for medical care and resources to be collocated and matched to the requirements, a [US] Federal interagency medical response-planning group has developed a conceptual approach for responding to such nuclear and radiological incidents. The "RTR" system (comprising Radiation-specific TRiage, TReatment, TRansport sites) is designed to support medical care following a nuclear incident. Its purpose is to characterize, organize, and efficiently deploy appropriate materiel and personnel assets as close as physically possible to various categories of victims while preserving the safety of responders. The RTR system is not a medical triage system for individual patients. After an incident is characterized and safe perimeters are established, RTR sites should be determined in real-time that are based on the extent of destruction, environmental factors, residual radiation, available infrastructure, and transportation routes. Such RTR sites are divided into three types depending on their physical/situational relationship to the incident. The RTR1 sites are near the epicenter with residual radiation and include victims with blast injuries and other major traumatic injuries including radiation exposure; RTR2 sites are situated in relationship to the plume with varying amounts of residual radiation present, with most victims being ambulatory; and RTR3 sites are collection and transport sites with minimal or no radiation present or exposure risk and a victim population with a potential variety of injuries or radiation exposures. Medical Care sites are predetermined sites at which definitive medical care is given to those in immediate need of care. They include local/regional hospitals, medical centers, other

  10. A monoclonal antibody against the nuclear pore complex inhibits nucleocytoplasmic transport of protein and RNA in vivo

    PubMed Central

    1988-01-01

    A monoclonal antibody that reacts with proteins in the nuclear pore complex of rat liver (Snow, C. M., A. Senior, and L. Gerace. 1987. J. Cell Biol. 104:1143-1156) has been shown to cross react with similar components in Xenopus oocytes, as determined by immunofluorescence microscopy and immunoblotting. We have microinjected the antibody into oocytes to study the possible role of these polypeptides in nucleocytoplasmic transport. The antibody inhibits import of a large nuclear protein, nucleoplasmin, in a time- and concentration-dependent manner. It also inhibits export of 5S ribosomal RNA and mature tRNA, but has no effect on transcription or intranuclear tRNA processing. The antibody does not affect the rate of diffusion into the nucleus of two small proteins, myoglobin and ovalbumin, indicating that antibody binding does not result in occlusion of the channel for diffusion. This suggests that inhibition of protein and RNA transport occurs by binding of the antibody at or near components of the pore that participate in mediated transport. PMID:2459127

  11. Hepatobiliary transport of YM466, a novel factor Xa inhibitor, in rats.

    PubMed

    Mano, Yuji; Usui, Takashi; Kamimura, Hidetaka

    2006-01-01

    YM466, a novel factor Xa inhibitor, is a hydrophilic compound with a carboxylic acid moiety. Previous studies in rats have shown that YM466 does nor undergo metabolism but is excreted into the bile and urine in unchanged form. Thus, in this study, we investigated in vivo hepatobiliary transport, focusing in particular on multidrug resistance-associated protein 2 (Mrp2/Abcc2)-mediated transport. The hepatobiliary transport of YM466 was investigated after its systemic infusion into Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic rats (EHBRs), which lack Mrp2. When the binding of YM466 in the plasma and liver was examined, the bile-to-plasma concentration ratio and the liver-to-plasma concentration ratio for the unbound concentration in SDRs amounted to 32.2 and 2.83, respectively, suggesting concentrated transport. The bile-to-liver concentration ratio for the unbound concentration in EHBRs was not lower than that found for SDRs. These findings suggest that YM466 is excreted from the plasma into the bile in a concentrated manner; however, Mrp2 does not play a major role in biliary excretion.

  12. Modeling Np and Pu transport with a surface complexation model and spatially variant sorption capacities: Implications for reactive transport modeling and performance assessments of nuclear waste disposal sites

    USGS Publications Warehouse

    Glynn, P.D.

    2003-01-01

    simulation conditions. Functional behaviors that cannot be fit include concentration trend reversals and radionuclide desorption spikes. Other simulation results are fit successfully but the fitted parameters (Kd and dispersivity) vary significantly depending on simulation conditions (e.g. "infiltration" vs. "cleanup" conditions). Notably, an increase in the variance of the specified sorption capacities results in a marked increase in the dispersion of the radionuclides. The results presented have implications for the simulation of radionuclide migration in performance assessments of nuclear waste-disposal sites, for the future monitoring of those sites, and more generally for modeling contaminant transport in ground-water environments. ?? 2003 Published by Elsevier Science Ltd.

  13. Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation.

    PubMed

    Faria, Jerusa A Q A; de Andrade, Carolina; Goes, Alfredo M; Rodrigues, Michele A; Gomes, Dawidson A

    2016-09-01

    The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells. PMID:27462018

  14. Yes and Lyn play a role in nuclear translocation of the epidermal growth factor receptor.

    PubMed

    Iida, M; Brand, T M; Campbell, D A; Li, C; Wheeler, D L

    2013-02-01

    The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers. Cetuximab is an anti-EGFR antibody that has been approved for use in oncology. Previously we investigated mechanisms of resistance to cetuximab using a model derived from the non-small cell lung cancer line NCI-H226. We demonstrated that cetuximab-resistant clones (Ctx(R)) had increased nuclear localization of the EGFR. This process was mediated by Src family kinases (SFKs), and nuclear EGFR had a role in resistance to cetuximab. To better understand SFK-mediated nuclear translocation of EGFR, we investigated which SFK member(s) controlled this process as well as the EGFR tyrosine residues that are involved. Analyses of mRNA and protein expression indicated upregulation of the SFK members Yes (v-Yes-1 yamaguchi sarcoma viral oncogene) and Lyn (v-yes-1 Yamaguchi sarcoma viral-related oncogene homolog) in all Ctx(R) clones. Further, immunoprecipitation analysis revealed that EGFR interacts with Yes and Lyn in Ctx(R) clones, but not in cetuximab-sensitive (Ctx(S)) parental cells. Using RNAi interference, we found that knockdown of either Yes or Lyn led to loss of EGFR translocation to the nucleus. Conversely, overexpression of Yes or Lyn in low nuclear EGFR-expressing Ctx(S) parental cells led to increased nuclear EGFR. Chromatin immunoprecipitation (ChIP) assays confirmed nuclear EGFR complexes associated with the promoter of the known EGFR target genes B-Myb and iNOS. Further, all Ctx(R) clones exhibited upregulation of B-Myb and iNOS at the mRNA and protein levels. siRNAs directed at Yes or Lyn led to decreased binding of EGFR complexes to the B-Myb and iNOS promoters based on ChIP analyses. SFKs have been shown to phosphorylate EGFR on tyrosines 845 and 1101 (Y845 and Y1101), and mutation of Y1101, but not Y845, impaired nuclear entry of the EGFR. Taken together, our findings demonstrate that Yes and Lyn phosphorylate EGFR at Y1101, which influences EGFR

  15. Modulation of nuclear factor-κB activity can influence the susceptibility to systemic lupus erythematosus

    PubMed Central

    Kalergis, Alexis M; Iruretagoyena, Mirentxu I; Barrientos, Magaly J; González, Pablo A; Herrada, Andres A; Leiva, Eduardo D; Gutiérrez, Miguel A; Riedel, Claudia A; Bueno, Susan M; Jacobelli, Sergio H

    2009-01-01

    Autoimmune diseases, such as systemic lupus erythematosus (SLE), result from deficiencies in self-antigen tolerance processes, which require regulated dendritic cell (DC) function. In this study we evaluated the phenotype of DCs during the onset of SLE in a mouse model, in which deletion of the inhibitory receptor FcγRIIb leads to the production of anti-nuclear antibodies and glomerulonephritis. Splenic DCs from FcγRIIb-deficient mice suffering from SLE showed increased expression of co-stimulatory molecules. Furthermore, diseased mice showed an altered function of the nuclear factor-κB (NF-κB) transcription factor, which is involved in DC maturation. Compared with healthy animals, expression of the inhibitory molecule IκB-α was significantly decreased in mice suffering from SLE. Consistently, pharmacological inhibition of NF-κB activity in FcγRIIb-deficient mice led to reduced susceptibility to SLE and prevented symptoms, such as anti-nuclear antibodies and kidney damage. Our data suggest that the occurrence of SLE is significantly influenced by alterations of NF-κB function, which can be considered as a new therapeutic target for this disease. PMID:19016912

  16. Determining Sources and Transport of Nuclear Contamination in Hudson River Sediments with Plutonium, Neptunium, and Cesium isotope ratios

    NASA Astrophysics Data System (ADS)

    Kenna, T. C.; Chillrud, S. N.; Chaky, D. A.; Simpson, H. J.; McHugh, C. M.; Shuster, E. L.; Bopp, R. F.

    2004-12-01

    Different sources of radioactive contamination contain characteristic and identifiable isotopic signatures, which can be used to study sediment transport. We focus on Pu-239, Pu-240, Np-237 and Cs-137, which are strongly bound to fine grained sediments. The Hudson River drainage basin has received contamination from at least three separate sources: 1) global fallout from atmospheric testing of nuclear weapons, which contributed Pu, Np and Cs; 2) contamination resulting from reactor releases at the Indian Point Nuclear Power Plant (IPNPP) located on the Hudson River Estuary ˜70km north of New York Harbor, where records document releases of Cs-137; 3) contamination resulting from activities at the Knolls Atomic Power Laboratory (KAPL) located on the Mohawk River, where incomplete records document releases of Cs-137 but no mention is made of Pu or Np. Here we report measurements of Pu isotopes, Np-237 and Cs-137 for a series of sediment cores collected from various locations within the drainage basin: 1) Mohawk River downstream of KAPL, 2) Hudson River upstream of its confluence with the Mohawk River, and 3) lower Hudson River at a location in close proximity to IPNPP. In addition, we present data from selected samples from two other lower Hudson River locations: One site located ˜30km downstream of IPNPP and another ˜30km upstream of IPNPP. By comparing the isotopic ratios Pu-240/Pu-239, Np-237/Pu-239, and Cs-137/Pu-239, measured in fluvial sediments to mean global fallout values, it is possible to identify and resolve different sources of non-fallout contamination. To date, isotopic data for sediments indicate non-fallout sources of Pu-239, Pu-240, and Cs-137; Np-237, however, appears to originate from global fallout only. Mohawk River sediments downstream of KAPL exhibit enrichments in Pu-239, Pu-240, and Cs-137 that are 7 to 20 times higher than levels expected from global fallout as indicated from Np-237. The elevated levels, non-fallout isotopic signatures

  17. Synaptic GluN2B/CaMKII-α Signaling Induces Synapto-Nuclear Transport of ERK and Jacob

    PubMed Central

    Melgarejo da Rosa, Michelle; Yuanxiang, PingAn; Brambilla, Riccardo; Kreutz, Michael R.; Karpova, Anna

    2016-01-01

    A central pathway in synaptic plasticity couples N-Methyl-D-Aspartate-receptor (NMDAR)-signaling to the activation of extracellular signal-regulated kinases (ERKs) cascade. ERK-dependency has been demonstrated for several forms of synaptic plasticity as well as learning and memory and includes local synaptic processes but also long-distance signaling to the nucleus. It is, however, controversial how NMDAR signals are connected to ERK activation in dendritic spines and nuclear import of ERK. The synapto-nuclear messenger Jacob couples NMDAR-dependent Ca2+-signaling to CREB-mediated gene expression. Protein transport of Jacob from synapse to nucleus essentially requires activation of GluN2B-containing NMDARs. Subsequent phosphorylation and binding of ERK1/2 to and ERK-dependent phosphorylation of serine 180 in Jacob encodes synaptic but not extrasynaptic NMDAR activation. In this study we show that stimulation of synaptic NMDAR in hippocampal primary neurons and induction of long-term potentiation (LTP) in acute slices results in GluN2B-dependent activation of CaMKII-α and subsequent nuclear import of active ERK and serine 180 phosphorylated Jacob. On the contrary, no evidence was found that either GluN2A-containing NMDAR or RasGRF2 are upstream of ERK activation and nuclear import of Jacob and ERK. PMID:27559307

  18. Synaptic GluN2B/CaMKII-α Signaling Induces Synapto-Nuclear Transport of ERK and Jacob.

    PubMed

    Melgarejo da Rosa, Michelle; Yuanxiang, PingAn; Brambilla, Riccardo; Kreutz, Michael R; Karpova, Anna

    2016-01-01

    A central pathway in synaptic plasticity couples N-Methyl-D-Aspartate-receptor (NMDAR)-signaling to the activation of extracellular signal-regulated kinases (ERKs) cascade. ERK-dependency has been demonstrated for several forms of synaptic plasticity as well as learning and memory and includes local synaptic processes but also long-distance signaling to the nucleus. It is, however, controversial how NMDAR signals are connected to ERK activation in dendritic spines and nuclear import of ERK. The synapto-nuclear messenger Jacob couples NMDAR-dependent Ca(2+)-signaling to CREB-mediated gene expression. Protein transport of Jacob from synapse to nucleus essentially requires activation of GluN2B-containing NMDARs. Subsequent phosphorylation and binding of ERK1/2 to and ERK-dependent phosphorylation of serine 180 in Jacob encodes synaptic but not extrasynaptic NMDAR activation. In this study we show that stimulation of synaptic NMDAR in hippocampal primary neurons and induction of long-term potentiation (LTP) in acute slices results in GluN2B-dependent activation of CaMKII-α and subsequent nuclear import of active ERK and serine 180 phosphorylated Jacob. On the contrary, no evidence was found that either GluN2A-containing NMDAR or RasGRF2 are upstream of ERK activation and nuclear import of Jacob and ERK. PMID:27559307

  19. Calculated transport properties of CdO: Thermal conductivity and thermoelectric power factor

    NASA Astrophysics Data System (ADS)

    Lindsay, L.; Parker, D. S.

    2015-10-01

    We present first-principles calculations of the thermal and electronic transport properties of the oxide semiconductor CdO. In particular, we find from theory that the accepted thermal conductivity κ value of 0.7 W m-1K-1 is approximately one order of magnitude too small; our calculations of κ of CdO are in good agreement with recent measurements. We also find that alloying of MgO with CdO is an effective means to reduce the lattice contribution to κ , despite MgO having a much larger thermal conductivity. We further consider the electronic structure of CdO in relation to thermoelectric performance, finding that large thermoelectric power factors may occur if the material can be heavily doped p type. This work develops insight into the nature of thermal and electronic transport in an important oxide semiconductor.

  20. Calculated transport properties of CdO: thermal conductivity and thermoelectric power factor

    DOE PAGES

    Lindsay, Lucas R.; Parker, David S.

    2015-10-01

    We present first principles calculations of the thermal and electronic transport properties of the oxide semiconductor CdO. In particular, we find from theory that the accepted thermal conductivity κ value of 0.7 Wm-1K-1 is approximately one order of magnitude too small; our calculations of κ of CdO are in good agreement with recent measurements. We also find that alloying of MgO with CdO is an effective means to reduce the lattice contribution to κ, despite MgO having a much larger thermal conductivity. We further consider the electronic structure of CdO in relation to thermoelectric performance, finding that large thermoelectric powermore » factors may occur if the material can be heavily doped p-type. This work develops insight into the nature of thermal and electronic transport in an important oxide semiconductor.« less

  1. Calculated transport properties of CdO: thermal conductivity and thermoelectric power factor

    SciTech Connect

    Lindsay, Lucas R.; Parker, David S.

    2015-10-01

    We present first principles calculations of the thermal and electronic transport properties of the oxide semiconductor CdO. In particular, we find from theory that the accepted thermal conductivity κ value of 0.7 Wm-1K-1 is approximately one order of magnitude too small; our calculations of κ of CdO are in good agreement with recent measurements. We also find that alloying of MgO with CdO is an effective means to reduce the lattice contribution to κ, despite MgO having a much larger thermal conductivity. We further consider the electronic structure of CdO in relation to thermoelectric performance, finding that large thermoelectric power factors may occur if the material can be heavily doped p-type. This work develops insight into the nature of thermal and electronic transport in an important oxide semiconductor.

  2. Analysis of thermally-stable electron transport factors from the hyperthermophilic archaebacterium Pyrodictium brockii

    SciTech Connect

    Not Available

    1992-09-01

    The mechanisms by which hyperthermophilic archaebacteria grow and carry out metabolic functions at elevated temperatures have yet to be determined. The objective of this work is to develop an understanding of the metabolic characteristics of, and the electron transport enzymes involved in, hydrogen/sulfur transformation by hyperthermophilic archaebacteria. Efforts focus on the autotrophic H{sub 2}-oxidizing bacterium, Pyrodictium brockii which has an optimum growth temperature of 105{degrees}C. Biochemical and genetic characterization of enzymes involved in hydrogen oxidizing electron transport pathway. These including investigating the role of the membrane lipids in protecting the hydrogenase enzyme from thermal inactivation, characterization of a quinone and a c-type cytochrome, and analysis of the topology in the membrane in the net energy generating components are reported. The long-term goal is to understand some of the factors contributing to the biochemical basis of extreme thermophily.

  3. Analysis of thermally-stable electron transport factors from the hyperthermophilic archaebacterium Pyrodictium brockii. Progress report

    SciTech Connect

    Not Available

    1992-09-01

    The mechanisms by which hyperthermophilic archaebacteria grow and carry out metabolic functions at elevated temperatures have yet to be determined. The objective of this work is to develop an understanding of the metabolic characteristics of, and the electron transport enzymes involved in, hydrogen/sulfur transformation by hyperthermophilic archaebacteria. Efforts focus on the autotrophic H{sub 2}-oxidizing bacterium, Pyrodictium brockii which has an optimum growth temperature of 105{degrees}C. Biochemical and genetic characterization of enzymes involved in hydrogen oxidizing electron transport pathway. These including investigating the role of the membrane lipids in protecting the hydrogenase enzyme from thermal inactivation, characterization of a quinone and a c-type cytochrome, and analysis of the topology in the membrane in the net energy generating components are reported. The long-term goal is to understand some of the factors contributing to the biochemical basis of extreme thermophily.

  4. Chair Report Consultancy Meeting on Nuclear Security Assessment Methodologies (NUSAM) Transport Case Study Working Group

    SciTech Connect

    Shull, Doug

    2015-08-19

    The purpose of the consultancy assignment was to (i) apply the NUSAM assessment methods to hypothetical transport security table top exercise (TTX) analyses and (ii) document its results to working materials of NUSAM case study on transport. A number of working group observations, using the results of TTX methodologies, are noted in the report.

  5. Cyclooxygenase-2 inhibitor, celecoxib, inhibits leiomyoma cell proliferation through the nuclear factor κB pathway.

    PubMed

    Park, Seung Bin; Jee, Byung Chul; Kim, Seok Hyun; Cho, Yeon Jean; Han, Myoungseok

    2014-09-01

    Our aim was to investigate whether celecoxib, a cyclooxygenase 2 (COX-2) inhibitor, decreases the in vitro proliferation of leiomyoma cells if the inflammatory pathway is blocked. Menstruation is an inflammation of uterus that produces cytokines and prostanoids, but the inflammatory mechanism underlying the growth of leiomyoma remains unexplained. Using in vitro cultures of leiomyoma cells obtained from 5 patients who underwent hysterectomy, cell proliferation, inflammatory signaling, transcription factors, growth factors, and extracellular matrix were examined by (4,5-dimethylthiaxol-2-yi)-2,5-diphenyltetraxolium bromide assay, immunoblotting, and quantitative polymerase chain reaction. Prostaglandin E2 was used to induce menstruation-like condition in the cells. We found that celecoxib inhibited COX-2 through the expression of nuclear factor κB in the cells. Celcoxib also decreased the gene expression of interleukin 6, tumor necrosis factor α, collagen A, fibronectin, platelet-derived growth factor, epidermal growth factor, and transforming growth factor β. In conclusion, the present study indicated that celecoxib could inhibit leiomyoma cell proliferation through blocking the inflammatory pathway that is probably one of the mechanisms underlying its pathogenesis.

  6. Environmental factors influencing older adults’ walking for transportation: a study using walk-along interviews

    PubMed Central

    2012-01-01

    Background Current knowledge on the relationship between the physical environment and walking for transportation among older adults (≥ 65 years) is limited. Qualitative research can provide valuable information and inform further research. However, qualitative studies are scarce and fail to include neighborhood outings necessary to study participants’ experiences and perceptions while interacting with and interpreting the local social and physical environment. The current study sought to uncover the perceived environmental influences on Flemish older adults’ walking for transportation. To get detailed and context-sensitive environmental information, it used walk-along interviews. Methods Purposeful convenience sampling was used to recruit 57 older adults residing in urban or semi-urban areas. Walk-along interviews to and from a destination (e.g. a shop) located within a 15 minutes’ walk from the participants’ home were conducted. Content analysis was performed using NVivo 9 software (QSR International). An inductive approach was used to derive categories and subcategories from the data. Results Data were categorized in the following categories and subcategories: access to facilities (shops & services, public transit, connectivity), walking facilities (sidewalk quality, crossings, legibility, benches), traffic safety (busy traffic, behavior of other road users), familiarity, safety from crime (physical factors, other persons), social contacts, aesthetics (buildings, natural elements, noise & smell, openness, decay) and weather. Conclusions The findings indicate that to promote walking for transportation a neighborhood should provide good access to shops and services, well-maintained walking facilities, aesthetically appealing places, streets with little traffic and places for social interaction. In addition, the neighborhood environment should evoke feelings of familiarity and safety from crime. Future quantitative studies should investigate if (changes

  7. Concept for a shuttle-tended reusable interplanetary transport vehicle using nuclear electric propulsion

    NASA Technical Reports Server (NTRS)

    Nakagawa, R. Y.; Elliot, J. C.; Spilker, T. R.; Grayson, C. M.

    2003-01-01

    NASA has placed new emphasis on the development of advanced propulsion technologies including Nuclear Electric Propulsion (NEP). This technology would provide multiple benefits including high delta-V capability and high power for long duration spacecraft operations.

  8. Nuclear Electric Propulsion: A ``Better, Safer, Cheaper'' Transportation System for Human Exploration of Mars

    NASA Astrophysics Data System (ADS)

    Clark, John S.; George, Jeffrey A.; Gefert, Leon P.; Doherty, Michael P.; Sefcik, Robert J.

    1994-07-01

    NASA has completed a preliminary mission and systems study of nuclear electric propulsion (NEP) systems for ``split-sprint'' human exploration and related robotic cargo missions to Mars. This paper describes the study, the mission architecture selected, the NEP system and technology development needs, proposed development schedules, and estimated development costs. Since current administration policy makers have delayed funding for key technology development activities that could make Mars exploration missions a reality in the near future, NASA will have time to evaluate various alternate mission options, and it appears prudent to ensure that Mars mission plans focus on astronaut and mission safety, while reducing costs to acceptable levels. The split-sprint nuclear electric propulsion system offers trip times comparable to nuclear thermal propulsion (NTP) systems, while providing mission abort opportunities that are not possible with ``reference'' mission architectures. Thus, NEP systems offer short transit times for the astronauts, reducing the exposure of the crew to intergalactic cosmic radiation. The high specific impulse of the NEP system, which leads to very low propellant requirements, results in significantly lower ``initial mass in low earth orbit'' (IMLEO). Launch vehicle packaging studies show that the NEP system can be launched, assembled, and deployed, with about one less 240-metric-ton heavy lift launch vehicle (HLLV) per mission opportunity - a very large cost savings! Technology development cost of the nuclear reactor for an NEP system would be shared with the proposed nuclear surface power systems, since nuclear systems will be required to provide substantial electrical power on the surface of Mars. The NEP development project plan proposed includes evolutionary technology development for nuclear electric propulsion systems that expands upon SP-100 (Space Power - 100 kw) technology that has been developed for lunar and Mars surface nuclear power

  9. Role of the liver-enriched transcription factor hepatocyte nuclear factor 1 in transcriptional regulation of the factor V111 gene.

    PubMed

    McGlynn, L K; Mueller, C R; Begbie, M; Notley, C R; Lillicrap, D

    1996-05-01

    Coagulation factor VIII is an essential cofactor required for normal hemostatic function. A deficiency in factor VIII results in the bleeding disorder hemophilia A. Despite the fact that the factor VIII gene was cloned a decade ago, the mechanisms which control its transcription remain unresolved. In our studies, we have characterized 12 protein binding sites within the factor VIII promoter by DNase I protection assays performed with rat liver nuclear extracts. Three of these elements (sites 1 to 3) are situated within the 5' untranslated region of the gene, while three other sites (sites 4 to 6) lie within the first 100 bp upstream of the transcriptional start site. We have identified an additional site (site 7) approximately 300 bp upstream from site 6, as well as a cluster of five sites in a 250-bp region which terminates approximately 1 kb from the transcriptional start site. Seven of these binding sites (sites 2, 3, 4, 6, 7, 9, and 10) bind members of the C/EBP family of transcription factors. DBP also binds to five of these sites (sites 3, 4, 6, 7, and 9). Utilizing transient transfection studies in HepG2 cells, we have shown that deletion of the factor VIII promoter sequences distal to nucleotide -44 results in a significant but small increase in promoter activity. The activity of each of the various 5' deletion constructs is significantly enhanced by cotransfection of C/EBPalpha and D-site-binding protein expression plasmids, while cotransfection of both C/EBPalpha and C/EBPbeta plasmids resulted in a further enhancement of transactivation. These studies also provide evidence of a repressor element located between nucleotides -740 and -1002. Since the minimal promoter sequence (-44 to +148) maintains the transcriptional activity of the full-length promoter sequence, we proceeded to identify additional factors binding to sites 1 to 4. Competition studies revealed that a ubiquitous transcription factor, NF-Y, binds to site 4, while the liver

  10. Nuclear electric propulsion: A better, safer, cheaper transportation system for human exploration of Mars

    NASA Technical Reports Server (NTRS)

    Clark, John S.; George, Jeffrey A.; Gefert, Leon P.; Doherty, Michael P.; Sefcik, Robert J.

    1994-01-01

    NASA has completed a preliminary mission and systems study of nuclear electric propulsion (NEP) systems for 'split-sprint' human exploration and related robotic cargo missions to Mars. This paper describes the study, the mission architecture selected, the NEP system and technology development needs, proposed development schedules, and estimated development costs. Since current administration policy makers have delayed funding for key technology development activities that could make Mars exploration missions a reality in the near future, NASA will have time to evaluate various alternate mission options, and it appears prudent to ensure that Mars mission plans focus on astronaut and mission safety, while reducing costs to acceptable levels. The split-sprint nuclear electric propulsion system offers trip times comparable to nuclear thermal propulsion (NTP) systems, while providing mission abort opportunities that are not possible with 'reference' mission architectures. Thus, NEP systems offer short transit times for the astronauts, reducing the exposure of the crew to intergalactic cosmic radiation. The high specific impulse of the NEP system, which leads to very low propellant requirements, results in significantly lower 'initial mass in low earth orbit' (IMLEO). Launch vehicle packaging studies show that the NEP system can be launched, assembled, and deployed, with about one less 240-metric-ton heavy lift launch vehicle (HLLV) per mission opportunity - a very Technology development cost of the nuclear reactor for an NEP system would be shared with the proposed nuclear surface power systems, since nuclear systems will be required to provide substantial electrical power on the surface of Mars. The NEP development project plan proposed includes evolutionary technology development for nuclear electric propulsion systems that expands upon SP-100 (Space Power - 100 kw(e)) technology that has been developed for lunar and Mars surface nuclear power, and small NEP systems

  11. Nuclear electric propulsion: A better, safer, cheaper transportation system for human exploration of Mars

    NASA Astrophysics Data System (ADS)

    Clark, John S.; George, Jeffrey A.; Gefert, Leon P.; Doherty, Michael P.; Sefcik, Robert J.

    1994-03-01

    NASA has completed a preliminary mission and systems study of nuclear electric propulsion (NEP) systems for 'split-sprint' human exploration and related robotic cargo missions to Mars. This paper describes the study, the mission architecture selected, the NEP system and technology development needs, proposed development schedules, and estimated development costs. Since current administration policy makers have delayed funding for key technology development activities that could make Mars exploration missions a reality in the near future, NASA will have time to evaluate various alternate mission options, and it appears prudent to ensure that Mars mission plans focus on astronaut and mission safety, while reducing costs to acceptable levels. The split-sprint nuclear electric propulsion system offers trip times comparable to nuclear thermal propulsion (NTP) systems, while providing mission abort opportunities that are not possible with 'reference' mission architectures. Thus, NEP systems offer short transit times for the astronauts, reducing the exposure of the crew to intergalactic cosmic radiation. The high specific impulse of the NEP system, which leads to very low propellant requirements, results in significantly lower 'initial mass in low earth orbit' (IMLEO). Launch vehicle packaging studies show that the NEP system can be launched, assembled, and deployed, with about one less 240-metric-ton heavy lift launch vehicle (HLLV) per mission opportunity - a very Technology development cost of the nuclear reactor for an NEP system would be shared with the proposed nuclear surface power systems, since nuclear systems will be required to provide substantial electrical power on the surface of Mars. The NEP development project plan proposed includes evolutionary technology development for nuclear electric propulsion systems that expands upon SP-100 (Space Power - 100 kw(e)) technology that has been developed for lunar and Mars surface nuclear power, and small NEP systems

  12. Nuclear electric propulsion: A better, safer, cheaper transportation system for human exploration of Mars

    SciTech Connect

    Clark, J.S.; George, J.A.; Gefert, L.P.; Doherty, M.P.; Sefcik, R.J.

    1994-03-01

    NASA has completed a preliminary mission and systems study of nuclear electric propulsion (NEP) systems for split-sprint' human exploration and related robotic cargo missions to Mars. This paper describes the study, the mission architecture selected, the NEP system and technology development needs, proposed development schedules, and estimated development costs. Since current administration policy makers have delayed funding for key technology development activities that could make Mars exploration missions a reality in the near future, NASA will have time to evaluate various alternate mission options, and it appears prudent to ensure that Mars mission plans focus on astronaut and mission safety, while reducing costs to acceptable levels. The split-sprint nuclear electric propulsion system offers trip times comparable to nuclear thermal propulsion (NTP) systems, while providing mission abort opportunities that are not possible with reference' mission architectures. Thus, NEP systems offer short transit times for the astronauts, reducing the exposure of the crew to intergalactic cosmic radiation. The high specific impulse of the NEP system, which leads to very low propellant requirements, results in significantly lower initial mass in low earth orbit' (IMLEO). Launch vehicle packaging studies show that the NEP system can be launched, assembled, and deployed, with about one less 240-metric-ton heavy lift launch vehicle (HLLV) per mission opportunity - a very Technology development cost of the nuclear reactor for an NEP system would be shared with the proposed nuclear surface power systems, since nuclear systems will be required to provide substantial electrical power on the surface of Mars. The NEP development project plan proposed includes evolutionary technology development for nuclear electric propulsion systems that expands upon SP-100 (Space Power - 100 kw(e)) technology that has been developed for lunar and Mars surface nuclear power.

  13. The GLFG repetitive region of the nucleoporin Nup116p interacts with Kap95p, an essential yeast nuclear import factor

    PubMed Central

    1995-01-01

    Nup116p is a member of a family of five yeast nuclear pore complex (NPC) proteins that share an amino terminal region of repetitive tetrapeptide "GLFG" motifs. Previous experiments characterized the unique morphological perturbations that occur in a nup116 null mutant: temperature-sensitive formation of nuclear envelope seals over the cytoplasmic face of the NPC (Wente, S. R., and G. Blobel. 1993. J. Cell Biol. 123:275-284). Three approaches have been taken to dissect the structural basis for Nup116p's role in NPC function. First, deletion mutagenesis analysis of NUP116 revealed that the GLFG region was required for NPC function. This was not true for the other four yeast GLFG family members (Nup49p, Nup57p, Nup100p, and Nup145p). Moreover, deletion of either half of Nup116p's GLFG repeats or replacement of Nup116p's GLFG region with either Nup100p's GLFG region or Nsp1p's FXFG repetitive region abolishes the function of Nup116p. At a semipermissive growth temperature, the cells lacking Nup116p's GLFG region displayed a diminished capacity for nuclear import. Second, overexpression of Nup116p's GLFG region severely inhibited cell growth, rapidly blocked polyadenylated-RNA export, and fragmented the nucleolus. Although it inhibited nuclear export, the overexpressed GLFG region appeared predominantly localized in the cytoplasm and NPC/nuclear envelope structure was not perturbed in thin section electron micrographs. Finally, using biochemical and two-hybrid analysis, an interaction was characterized between Nup116p's GLFG region and Kap95p, an essential yeast homologue of the vertebrate nuclear import factor p97/Imp90/karopherin beta. These data show that Nup116p's GLFG region has an essential role in mediating nuclear transport. PMID:8557738

  14. Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development▿

    PubMed Central

    Ai, Di; Wang, Jun; Amen, Melanie; Lu, Mei-Fang; Amendt, Brad A.; Martin, James F.

    2007-01-01

    Pitx2, a paired-related homeobox gene that is mutated in Rieger syndrome I, is the earliest known marker of oral ectoderm. Pitx2 was previously shown to be required for tooth, palate, and pituitary development in mice; however, the mechanisms regulating Pitx2 transcription in the oral ectoderm are poorly understood. Here we used an in vivo transgenic approach to investigate the mechanisms regulating Pitx2 transcription. We identified a 7-kb fragment that directs LacZ expression in oral ectoderm and in many of its derivatives. Deletion analysis of transgenic embryos reduced this fragment to a 520-bp region that directed LacZ activity to Rathke's pouch. A comparison of the mouse and human sequences revealed a conserved nuclear factor 1 (NF-1) recognition element near a consensus T-cell factor (TCF)/LEF binding site. The mutation of either site individually abolished LacZ activity in transgenic embryos, identifying Pitx2 as a direct target of Wnt signaling in pituitary development. These findings uncover a requirement for NF-1 and TCF factors in Pitx2 transcriptional regulation in the pituitary and provide insight into the mechanisms controlling region-specific transcription in the oral ectoderm and its derivatives. PMID:17562863

  15. Hydrogen-isotope transport in an ELBRODUR G CuCrZr alloy for nuclear applications in heat sinks

    NASA Astrophysics Data System (ADS)

    Noh, S. J.; Byeon, W. J.; Shin, H. W.; Kim, H. S.; Kim, Jaeyong; Lee, S. K.; Kim, Jaewoo

    2016-05-01

    We present the first complete data set of the transport parameters (permeability, diffusivity, and solubility) of hydrogen and deuterium in an ELBRODUR G precipitation hardened CuCrZr alloy experimentally measured by using the time-dependent gas-phase technique in an elevated temperature range of 300-600 °C for nuclear applications in heat sinks. Using the measured values for hydrogen and deuterium and a quantum mechanical model based on a harmonic approximation, an extrapolation for tritium is also presented. The isotope effect ratios for the transport parameters were also estimated. Furthermore, our hydrogen results for ELBRODUR G were compared with the results for other copper alloys previously reported by other authors.

  16. Discrete-event simulation of nuclear-waste transport in geologic sites subject to disruptive events. Final report

    SciTech Connect

    Aggarwal, S.; Ryland, S.; Peck, R.

    1980-06-19

    This report outlines a methodology to study the effects of disruptive events on nuclear waste material in stable geologic sites. The methodology is based upon developing a discrete events model that can be simulated on the computer. This methodology allows a natural development of simulation models that use computer resources in an efficient manner. Accurate modeling in this area depends in large part upon accurate modeling of ion transport behavior in the storage media. Unfortunately, developments in this area are not at a stage where there is any consensus on proper models for such transport. Consequently, our work is directed primarily towards showing how disruptive events can be properly incorporated in such a model, rather than as a predictive tool at this stage. When and if proper geologic parameters can be determined, then it would be possible to use this as a predictive model. Assumptions and their bases are discussed, and the mathematical and computer model are described.

  17. Simulating Effects of Non-Isothermal Flow on Reactive Transport of Radionuclides Originating from an Underground Nuclear Test

    SciTech Connect

    Carle, S F; Zavarin, M; Shumaker, D E; Tompson, A B; Maxwell, R M; Pawloski, G A

    2006-03-06

    Temperature can significantly affect radionuclide transport behavior. In simulation of radionuclide transport originating from an underground nuclear test, temperature effects from residual test heat include non-isothermal groundwater flow behavior (e.g. convection cells), increased dissolution rates of melt glass containing refractory radionuclides, changes in water chemistry, and, in turn, changes in radionuclide sorption behavior. The low-yield (0.75 kiloton) Cambric underground nuclear test situated in alluvium below the water table offers unique perspectives on radionuclide transport in groundwater. The Cambric test was followed by extensive post-test characterization of the radionuclide source term and a 16-year pumping-induced radionuclide migration experiment that captured more mobile radionuclides in groundwater. Discharge of pumped groundwater caused inadvertent recirculation of radionuclides through a 220-m thick vadose zone to the water table and below, including partial re-capture in the pumping well. Non-isothermal flow simulations indicate test-related heat persists at Cambric for about 10 years and induces limited thermal convection of groundwater. The test heat has relatively little impact on mobilizing radionuclides compared to subsequent pumping effects. However, our reactive transport models indicate test-related heat can raise melt glass dissolution rates up to 10{sup 4} faster than at ambient temperatures depending on pH and species activities. Non-isothermal flow simulations indicate that these elevated glass dissolution rates largely decrease within 1 year. Thermally-induced increases in fluid velocity may also significantly increase rates of melt glass dissolution by changing the fluid chemistry in contact with the dissolving glass.

  18. Nuclear transport receptor binding avidity triggers a self-healing collapse transition in FG-nucleoporin molecular brushes

    PubMed Central

    Schoch, Rafael L.; Kapinos, Larisa E.; Lim, Roderick Y. H.

    2012-01-01

    Conformational changes at supramolecular interfaces are fundamentally coupled to binding activity, yet it remains a challenge to probe this relationship directly. Within the nuclear pore complex, this underlies how transport receptors known as karyopherins proceed through a tethered layer of intrinsically disordered nucleoporin domains containing Phe-Gly (FG)-rich repeats (FG domains) that otherwise hinder passive transport. Here, we use nonspecific proteins (i.e., BSA) as innate molecular probes to explore FG domain conformational changes by surface plasmon resonance. This mathematically diminishes the surface plasmon resonance refractive index constraint, thereby providing the means to acquire and correlate height changes in a surface-tethered FG domain layer to Kap binding affinities in situ with respect to their relative spatial arrangements. Stepwise measurements show that FG domain collapse is caused by karyopherin β1 (Kapβ1) binding at low concentrations, but this gradually transitions into a reextension at higher Kapβ1 concentrations. This ability to self-heal is intimately coupled to Kapβ1-FG binding avidity that promotes the maximal incorporation of Kapβ1 into the FG domain layer. Further increasing Kapβ1 to physiological concentrations leads to a “pileup” of Kapβ1 molecules that bind weakly to unoccupied FG repeats at the top of the layer. Therefore, binding avidity does not hinder fast transport per se. Revealing the biophysical basis underlying the form–function relationship of Kapβ1-FG domain behavior results in a convergent picture in which transport and mechanistic aspects of nuclear pore complex functionality are reconciled. PMID:23043112

  19. Atmospheric transport of radionuclides emitted due to wildfires near the Chernobyl Nuclear Power Plant in 2015

    NASA Astrophysics Data System (ADS)

    Evangeliou, Nikolaos; Zibtsev, Sergey; Myroniuk, Viktor; Zhurba, Marina; Hamburger, Thomas; Stohl, Andreas; Balkanski, Yves; Paugam, Ronan; Mousseau, Timothy A.; Møller, Anders P.; Kireev, Sergey I.

    2016-04-01

    In 2015, two major fires in the Chernobyl Exclusion Zone (CEZ) have caused concerns about the secondary radioactive contamination that might have spread over Europe. The total active burned area was estimated to be about 15,000 hectares, of which 9000 hectares burned in April and 6000 hectares in August. The present paper aims to assess, for the first time, the transport and impact of these fires over Europe. For this reason, direct observations of the prevailing deposition levels of 137Cs and 90Sr, 238Pu, 239Pu, 240Pu and 241Am in the CEZ were processed together with burned area estimates. Based on literature reports, we made the conservative assumption that 20% of the deposited labile radionuclides 137Cs and 90Sr, and 10% of the more refractory 238Pu, 239Pu, 240Pu and 241Am, were resuspended by the fires. We estimate that about 10.9 TBq of 137Cs, 1.5 TBq of 90Sr, 7.8 GBq of 238Pu, 6.3 GBq of 239Pu, 9.4 GBq of 240Pu and 29.7 GBq of 241Am were released from both fire events. These releases could be classified as of "Level 3" on the relative INES (International Nuclear Events Scale) scale, which corresponds to a serious incident, in which non-lethal deterministic effects are expected from radiation. To simulate the dispersion of the resuspended radionuclides in the atmosphere and their deposition onto the terrestrial environment, we used a Lagrangian dispersion model. Spring fires redistributed radionuclides over the northern and eastern parts of Europe, while the summer fires also affected Central and Southern Europe. The more labile elements escaped more easily from the CEZ and then reached and deposited in areas far from the source, whereas the larger refractory particles were removed more efficiently from the atmosphere and thus did mainly affect the CEZ and its vicinity. For the spring 2015 fires, we estimate that about 80% of 137Cs and 90Sr and about 69% of 238Pu, 239Pu, 240Pu and 241Am were deposited over areas outside the CEZ. 93% of the labile and 97% of

  20. Long-range tropospheric transport of uranium and plutonium weapons fallout from Semipalatinsk nuclear test site to Norway.

    PubMed

    Wendel, Cato Christian; Fifield, L Keith; Oughton, Deborah H; Lind, Ole Christian; Skipperud, Lindis; Bartnicki, Jerzy; Tims, Stephen G; Høibråten, Steinar; Salbu, Brit

    2013-09-01

    A combination of state-of-the-art isotopic fingerprinting techniques and atmospheric transport modelling using real-time historical meteorological data has been used to demonstrate direct tropospheric transport of radioactive debris from specific nuclear detonations at the Semipalatinsk test site in Kazakhstan to Norway via large areas of Europe. A selection of archived air filters collected at ground level at 9 stations in Norway during the most intensive atmospheric nuclear weapon testing periods (1957-1958 and 1961-1962) has been screened for radioactive particles and analysed with respect to the concentrations and atom ratios of plutonium (Pu) and uranium (U) using accelerator mass spectrometry (AMS). Digital autoradiography screening demonstrated the presence of radioactive particles in the filters. Concentrations of (236)U (0.17-23nBqm(-3)) and (239+240)Pu (1.3-782μBqm(-3)) as well as the atom ratios (240)Pu/(239)Pu (0.0517-0.237) and (236)U/(239)Pu (0.0188-0.7) varied widely indicating several different sources. Filter samples from autumn and winter tended to have lower atom ratios than those sampled in spring and summer, and this likely reflects a tropospheric influence in months with little stratospheric fallout. Very high (236)U, (239+240)Pu and gross beta activity concentrations as well as low (240)Pu/(239)Pu (0.0517-0.077), (241)Pu/(239)Pu (0.00025-0.00062) and (236)U/(239)Pu (0.0188-0.046) atom ratios, characteristic of close-in and tropospheric fallout, were observed in filters collected at all stations in Nov 1962, 7-12days after three low-yield detonations at Semipalatinsk (Kazakhstan). Atmospheric transport modelling (NOAA HYSPLIT_4) using real-time meteorological data confirmed that long range transport of radionuclides, and possibly radioactive particles, from Semipalatinsk to Norway during this period was plausible. The present work shows that direct tropospheric transport of fallout from atmospheric nuclear detonations periodically may have

  1. Long-range tropospheric transport of uranium and plutonium weapons fallout from Semipalatinsk nuclear test site to Norway.

    PubMed

    Wendel, Cato Christian; Fifield, L Keith; Oughton, Deborah H; Lind, Ole Christian; Skipperud, Lindis; Bartnicki, Jerzy; Tims, Stephen G; Høibråten, Steinar; Salbu, Brit

    2013-09-01

    A combination of state-of-the-art isotopic fingerprinting techniques and atmospheric transport modelling using real-time historical meteorological data has been used to demonstrate direct tropospheric transport of radioactive debris from specific nuclear detonations at the Semipalatinsk test site in Kazakhstan to Norway via large areas of Europe. A selection of archived air filters collected at ground level at 9 stations in Norway during the most intensive atmospheric nuclear weapon testing periods (1957-1958 and 1961-1962) has been screened for radioactive particles and analysed with respect to the concentrations and atom ratios of plutonium (Pu) and uranium (U) using accelerator mass spectrometry (AMS). Digital autoradiography screening demonstrated the presence of radioactive particles in the filters. Concentrations of (236)U (0.17-23nBqm(-3)) and (239+240)Pu (1.3-782μBqm(-3)) as well as the atom ratios (240)Pu/(239)Pu (0.0517-0.237) and (236)U/(239)Pu (0.0188-0.7) varied widely indicating several different sources. Filter samples from autumn and winter tended to have lower atom ratios than those sampled in spring and summer, and this likely reflects a tropospheric influence in months with little stratospheric fallout. Very high (236)U, (239+240)Pu and gross beta activity concentrations as well as low (240)Pu/(239)Pu (0.0517-0.077), (241)Pu/(239)Pu (0.00025-0.00062) and (236)U/(239)Pu (0.0188-0.046) atom ratios, characteristic of close-in and tropospheric fallout, were observed in filters collected at all stations in Nov 1962, 7-12days after three low-yield detonations at Semipalatinsk (Kazakhstan). Atmospheric transport modelling (NOAA HYSPLIT_4) using real-time meteorological data confirmed that long range transport of radionuclides, and possibly radioactive particles, from Semipalatinsk to Norway during this period was plausible. The present work shows that direct tropospheric transport of fallout from atmospheric nuclear detonations periodically may have

  2. Factors Affecting the Corporate Decision-Making Process of Air Transport Manufacturers

    NASA Technical Reports Server (NTRS)

    Ollila, R. G.; Hill, J. D.; Noton, B. R.; Duffy, M. A.; Epstein, M. M.

    1976-01-01

    Fuel economy is a pivotal question influencing the future sale and utilization of commercial aircraft. The NASA Aircraft Energy Efficiency (ACEE) Program Office has a program intended to accelerate the readiness of advanced technologies for energy efficient aircraft. Because the decision to develop a new airframe or engine is a major financial hazard for manufacturers, it is important to know what factors influence the decision making process. A method is described for identifying and ranking individuals and organizations involved at each stage of commercial air transport development, and the barriers that must be overcome in adopting new technologies.

  3. Coupling of Nuclear Waste Form Corrosion and Radionuclide Transports in Presence of Relevant Repository Sediments

    SciTech Connect

    Wall, Nathalie A.; Neeway, James J.; Qafoku, Nikolla P.; Ryan, Joseph V.

    2015-09-30

    Assessments of waste form and disposal options start with the degradation of the waste forms and consequent mobilization of radionuclides. Long-term static tests, single-pass flow-through tests, and the pressurized unsaturated flow test are often employed to study the durability of potential waste forms and to help create models that predict their durability throughout the lifespan of the disposal site. These tests involve the corrosion of the material in the presence of various leachants, with different experimental designs yielding desired information about the behavior of the material. Though these tests have proved instrumental in elucidating various mechanisms responsible for material corrosion, the chemical environment to which the material is subject is often not representative of a potential radioactive waste repository where factors such as pH and leachant composition will be controlled by the near-field environment. Near-field materials include, but are not limited to, the original engineered barriers, their resulting corrosion products, backfill materials, and the natural host rock. For an accurate performance assessment of a nuclear waste repository, realistic waste corrosion experimental data ought to be modeled to allow for a better understanding of waste form corrosion mechanisms and the effect of immediate geochemical environment on these mechanisms. Additionally, the migration of radionuclides in the resulting chemical environment during and after waste form corrosion must be quantified and mechanisms responsible for migrations understood. The goal of this research was to understand the mechanisms responsible for waste form corrosion in the presence of relevant repository sediments to allow for accurate radionuclide migration quantifications. The rationale for this work is that a better understanding of waste form corrosion in relevant systems will enable increased reliance on waste form performance in repository environments and potentially

  4. Genes for the dimerization cofactor of hepatocyte nuclear factor-1[alpha] (DCOH) are on human and murine chromsomes 10

    SciTech Connect

    Milatovich, A.; Mendel, D.B.; Crabtree, G.R.; Francke, U. )

    1993-04-01

    Hepatocyte nuclear factor-1[alpha] (HNF-1[alpha]; gene symbol, TCF1) forms dimers with itself as well as with HNF-1[beta] and regulates the expression of several liver-specific genes. Recently, a dimerization cofactor of hepatocyte nuclear factor-1[alpha], called DCOH, has been identified. Here, the authors report the chromosomal localization of the genes for this cofactor to chromosomes 10 in both humans and mice by Southern blot analyses of somatic cell hybrids. 25 refs., 1 fig., 2 tabs.

  5. Spent nuclear fuel project, Cold Vacuum Drying Facility human factors engineering (HFE) analysis: Results and findings

    SciTech Connect

    Garvin, L.J.

    1998-07-17

    This report presents the background, methodology, and findings of a human factors engineering (HFE) analysis performed in May, 1998, of the Spent Nuclear Fuels (SNF) Project Cold Vacuum Drying Facility (CVDF), to support its Preliminary Safety Analysis Report (PSAR), in responding to the requirements of Department of Energy (DOE) Order 5480.23 (DOE 1992a) and drafted to DOE-STD-3009-94 format. This HFE analysis focused on general environment, physical and computer workstations, and handling devices involved in or directly supporting the technical operations of the facility. This report makes no attempt to interpret or evaluate the safety significance of the HFE analysis findings. The HFE findings presented in this report, along with the results of the CVDF PSAR Chapter 3, Hazards and Accident Analyses, provide the technical basis for preparing the CVDF PSAR Chapter 13, Human Factors Engineering, including interpretation and disposition of findings. The findings presented in this report allow the PSAR Chapter 13 to fully respond to HFE requirements established in DOE Order 5480.23. DOE 5480.23, Nuclear Safety Analysis Reports, Section 8b(3)(n) and Attachment 1, Section-M, require that HFE be analyzed in the PSAR for the adequacy of the current design and planned construction for internal and external communications, operational aids, instrumentation and controls, environmental factors such as heat, light, and noise and that an assessment of human performance under abnormal and emergency conditions be performed (DOE 1992a).

  6. Nuclear factor I and cerebellar granule neuron development: an intrinsic-extrinsic interplay.

    PubMed

    Kilpatrick, Daniel L; Wang, Wei; Gronostajski, Richard; Litwack, E David

    2012-03-01

    Granule neurons have a central role in cerebellar function via their synaptic interactions with other neuronal cell types both within and outside this structure. Establishment of these synaptic connections and its control is therefore essential to their function. Both intrinsic as well as environmental mechanisms are required for neuronal development and formation of neuronal circuits, and a key but poorly understood question is how these various events are coordinated and integrated in maturing neurons. In this review, we summarize recent work on the role of the Nuclear Factor I family in the transcriptional programming of cerebellar granule neuron maturation and synapse formation. In particular, we describe (1) the involvement of this family of factors in key developmental steps occurring throughout postmitotic granule neuron development, including dendrite and synapse formation and synaptic receptor expression, and (2) the mediation of these actions by critical downstream gene targets that control cell-cell interactions. These findings illustrate how Nuclear Factor I proteins and their regulons function as a “bridge” between cell-intrinsic and cell-extrinsic interactions to control multiple phases of granule neuron development.

  7. The nuclear factor SPBP contains different functional domains and stimulates the activity of various transcriptional activators.

    PubMed

    Rekdal, C; Sjøttem, E; Johansen, T

    2000-12-22

    SPBP (stromelysin-1 platelet-derived growth factor-responsive element binding protein) was originally cloned from a cDNA expression library by virtue of its ability to bind to a platelet-derived growth factor-responsive element in the human stromelysin-1 promoter. A 937-amino acid-long protein was deduced from a 3995-nucleotide murine cDNA sequence. By analyses of both human and murine cDNAs, we now show that SPBP is twice as large as originally found. The human SPBP gene contains six exons and is located on chromosome 22q13.1-13.3. Two isoforms differing in their C termini are expressed due to alternative splicing. PCR analyses of multitissue cDNA panels showed that SPBP is expressed in most tissues except for ovary and prostate. Functional mapping revealed that SPBP is a nuclear, multidomain protein containing an N-terminal region with transactivating ability, a novel type of DNA-binding domain containing an AT hook motif, and a bipartite nuclear localization signal as well as a C-terminal zinc finger domain. This type of zinc finger domain is also found in the trithorax family of chromatin-based transcriptional regulator proteins. Using cotransfection experiments, we find that SPBP enhances the transcriptional activity of various transcription factors such as c-Jun, Ets1, Sp1, and Pax6. Hence, SPBP seems to act as a transcriptional coactivator. PMID:10995766

  8. 41 CFR 301-70.101 - What factors must we consider in determining which method of transportation results in the...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 4 2010-07-01 2010-07-01 false What factors must we consider in determining which method of transportation results in the greatest advantage to the Government... determining which method of transportation results in the greatest advantage to the Government? In selecting...

  9. INTRINSIC DOSIMETRY OF GLASS CONTAINERS USED TO TRANSPORT NUCLEAR MATERIALS: Potential Implications to the Field of Nuclear Forensics

    SciTech Connect

    Schwantes, Jon M.; Miller, Steven D.; Piper, Roman K.; Murphy, Mark K.; Amonette, James E.; Bonde, Steven E.; Duckworth, Douglas C.

    2008-09-15

    Thermoluminescence (TL) and Electron Paramagnetic Resonance (EPR) dosimetry were used to measure dose effects in borosilicate glass with time, from 10 minutes to ~60 days following exposure to a dose of up to 10,000 Rad. TL and EPR results were consistent and performed similarly, with both techniques capable of achieving an estimated limit of detection of between 50-100 Rad. Three peaks were identified in the TL glow curve at roughly 110oC, 205oC, and 225oC. The intensity of the 205oC peak was the dominant peak over the time period of this study. The stability of all of the peaks with time since irradiation increased with their corresponding temperature and little or no variation was observed in the glow curve response to a specified total dose attained at different dose rates. The intensity of the 205oC peak decreased logarithmically with time regardless of total dose. Based upon a conservative limit of detection of 330 Rad, a 10,000 Rad dose would still be detected 2.7E3 years after exposure. This paper introduces the concept of intrinsic dosimetry, the consideration of a measured dose received to container walls in concert with the physical characteristics of the radioactive material contained inside those walls, as a method for gathering rather unique pathway information about the history of that sample. Three hypothetical scenarios are presented to introduce this method and to illustrate how intrinsic dosimetry might benefit the fields of nuclear forensics and waste management.

  10. Structural and calorimetric studies demonstrate that the hepatocyte nuclear factor 1β (HNF1β) transcription factor is imported into the nucleus via a monopartite NLS sequence.

    PubMed

    Wiedmann, Mareike M; Aibara, Shintaro; Spring, David R; Stewart, Murray; Brenton, James D

    2016-09-01

    The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in ovarian clear cell carcinoma (CCC) and is a potential therapeutic target. To explore potential approaches that block HNF1β transcription we have identified and characterised extensively the nuclear localisation signal (NLS) for HNF1β and its interactions with the nuclear protein import receptor, Importin-α. Pull-down assays demonstrated that the DNA binding domain of HNF1β interacted with a spectrum of Importin-α isoforms and deletion constructs tagged with eGFP confirmed that the HNF1β (229)KKMRRNR(235) sequence was essential for nuclear localisation. We further characterised the interaction between the NLS and Importin-α using complementary biophysical techniques and have determined the 2.4Å resolution crystal structure of the HNF1β NLS peptide bound to Importin-α. The functional, biochemical, and structural characterisation of the nuclear localisation signal present on HNF1β and its interaction with the nuclear import protein Importin-α provide the basis for the development of compounds targeting transcription factor HNF1β via its nuclear import pathway.

  11. Applying Human Factors Evaluation and Design Guidance to a Nuclear Power Plant Digital Control System

    SciTech Connect

    Thomas Ulrich; Ronald Boring; William Phoenix; Emily Dehority; Tim Whiting; Jonathan Morrell; Rhett Backstrom

    2012-08-01

    The United States (U.S.) nuclear industry, like similar process control industries, has moved toward upgrading its control rooms. The upgraded control rooms typically feature digital control system (DCS) displays embedded in the panels. These displays gather information from the system and represent that information on a single display surface. In this manner, the DCS combines many previously separate analog indicators and controls into a single digital display, whereby the operators can toggle between multiple windows to monitor and control different aspects of the plant. The design of the DCS depends on the function of the system it monitors, but revolves around presenting the information most germane to an operator at any point in time. DCSs require a carefully designed human system interface. This report centers on redesigning existing DCS displays for an example chemical volume control system (CVCS) at a U.S. nuclear power plant. The crucial nature of the CVCS, which controls coolant levels and boration in the primary system, requires a thorough human factors evaluation of its supporting DCS. The initial digital controls being developed for the DCSs tend to directly mimic the former analog controls. There are, however, unique operator interactions with a digital vs. analog interface, and the differences have not always been carefully factored in the translation of an analog interface to a replacement DCS. To ensure safety, efficiency, and usability of the emerging DCSs, a human factors usability evaluation was conducted on a CVCS DCS currently being used and refined at an existing U.S. nuclear power plant. Subject matter experts from process control engineering, software development, and human factors evaluated the DCS displays to document potential usability issues and propose design recommendations. The evaluation yielded 167 potential usability issues with the DCS. These issues should not be considered operator performance problems but rather opportunities

  12. Nuclear factor 1 family members mediate repression of the BK virus late promoter.

    PubMed

    Kraus, R J; Shadley, L; Mertz, J E

    2001-08-15

    BK virus (BKV) is a member of the polyoma virus family that is ubiquitous in humans. Its 5-kb DNA genome consists of a bidirectional promoter region situated between two temporally regulated coding regions. We mapped the transcription initiation site of the major late promoter (MLP) of the archetype strain BKV(WW) to nt 185. We found that it lies within the sequence TGGN6GCCA, a binding site for members of the nuclear factor 1 (NF1) family of transcription factors. Competition electrophoretic mobility shift and immunoshift assays confirmed that NF1 factors present in nuclear extracts of HeLa and CV-1 cells bind to the BKV-MLP. Because BKV(WW) grew poorly in tissue culture and failed to express detectable levels of RNA in vitro, SV40-BKV chimeric viruses were constructed to investigate the transcriptional function of this NF-1 binding site. These sequence-specific factors repressed transcription in a cell-free system when template copy number was low. This repression could be relieved by the addition in trans of oligonucleotides containing wild-type, but not mutated, NF1-binding site sequences. SV40-BKV chimeric viruses defective in this NF1-binding site overproduced late RNA at early, but not late, times after transfection of CV-1 cells. Finally, transient expression in 293 cells of cDNAs encoding the family members NF1-A4, NF1-C2, and NF1-X2 specifically repressed transcription from the BKV late promoter approximately 3-, 10-, and 10-fold, respectively, in a DNA binding-dependent manner. We conclude that some members of the NF1 family of transcription factors can act as sequence-specific cellular repressors of the BKV-MLP. We propose that titration of these and other cellular repressors by viral genome amplification may be responsible in part for the replication-dependent component of the early-to-late switch in BKV gene expression.

  13. Control factors and scale analysis of annual river water, sediments and carbon transport in China

    PubMed Central

    Song, Chunlin; Wang, Genxu; Sun, Xiangyang; Chang, Ruiying; Mao, Tianxu

    2016-01-01

    Under the context of dramatic human disturbances on river system, the processes that control the transport of water, sediment, and carbon from river basins to coastal seas are not completely understood. Here we performed a quantitative synthesis for 121 sites across China to find control factors of annual river exports (Rc: runoff coefficient; TSSC: total suspended sediment concentration; TSSL: total suspended sediment loads; TOCL: total organic carbon loads) at different spatial scales. The results indicated that human activities such as dam construction and vegetation restoration might have a greater influence than climate on the transport of river sediment and carbon, although climate was a major driver of Rc. Multiple spatial scale analyses indicated that Rc increased from the small to medium scale by 20% and then decreased at the sizable scale by 20%. TSSC decreased from the small to sizeable scale but increase from the sizeable to large scales; however, TSSL significantly decreased from small (768 g·m−2·a−1) to medium spatial scale basins (258 g·m−2·a−1), and TOCL decreased from the medium to large scale. Our results will improve the understanding of water, sediment and carbon transport processes and contribute better water and land resources management strategies from different spatial scales. PMID:27166177

  14. Control factors and scale analysis of annual river water, sediments and carbon transport in China.

    PubMed

    Song, Chunlin; Wang, Genxu; Sun, Xiangyang; Chang, Ruiying; Mao, Tianxu

    2016-01-01

    Under the context of dramatic human disturbances on river system, the processes that control the transport of water, sediment, and carbon from river basins to coastal seas are not completely understood. Here we performed a quantitative synthesis for 121 sites across China to find control factors of annual river exports (Rc: runoff coefficient; TSSC: total suspended sediment concentration; TSSL: total suspended sediment loads; TOCL: total organic carbon loads) at different spatial scales. The results indicated that human activities such as dam construction and vegetation restoration might have a greater influence than climate on the transport of river sediment and carbon, although climate was a major driver of Rc. Multiple spatial scale analyses indicated that Rc increased from the small to medium scale by 20% and then decreased at the sizable scale by 20%. TSSC decreased from the small to sizeable scale but increase from the sizeable to large scales; however, TSSL significantly decreased from small (768 g·m(-2)·a(-1)) to medium spatial scale basins (258 g·m(-2)·a(-1)), and TOCL decreased from the medium to large scale. Our results will improve the understanding of water, sediment and carbon transport processes and contribute better water and land resources management strategies from different spatial scales. PMID:27166177

  15. Control factors and scale analysis of annual river water, sediments and carbon transport in China

    NASA Astrophysics Data System (ADS)

    Song, Chunlin; Wang, Genxu; Sun, Xiangyang; Chang, Ruiying; Mao, Tianxu

    2016-05-01

    Under the context of dramatic human disturbances on river system, the processes that control the transport of water, sediment, and carbon from river basins to coastal seas are not completely understood. Here we performed a quantitative synthesis for 121 sites across China to find control factors of annual river exports (Rc: runoff coefficient; TSSC: total suspended sediment concentration; TSSL: total suspended sediment loads; TOCL: total organic carbon loads) at different spatial scales. The results indicated that human activities such as dam construction and vegetation restoration might have a greater influence than climate on the transport of river sediment and carbon, although climate was a major driver of Rc. Multiple spatial scale analyses indicated that Rc increased from the small to medium scale by 20% and then decreased at the sizable scale by 20%. TSSC decreased from the small to sizeable scale but increase from the sizeable to large scales; however, TSSL significantly decreased from small (768 g·m‑2·a‑1) to medium spatial scale basins (258 g·m‑2·a‑1), and TOCL decreased from the medium to large scale. Our results will improve the understanding of water, sediment and carbon transport processes and contribute better water and land resources management strategies from different spatial scales.

  16. A Distributed Simulation Facility to Support Human Factors Research in Advanced Air Transportation Technology

    NASA Technical Reports Server (NTRS)

    Amonlirdviman, Keith; Farley, Todd C.; Hansman, R. John, Jr.; Ladik, John F.; Sherer, Dana Z.

    1998-01-01

    A distributed real-time simulation of the civil air traffic environment developed to support human factors research in advanced air transportation technology is presented. The distributed environment is based on a custom simulation architecture designed for simplicity and flexibility in human experiments. Standard Internet protocols are used to create the distributed environment, linking all advanced cockpit simulator, all Air Traffic Control simulator, and a pseudo-aircraft control and simulation management station. The pseudo-aircraft control station also functions as a scenario design tool for coordinating human factors experiments. This station incorporates a pseudo-pilot interface designed to reduce workload for human operators piloting multiple aircraft simultaneously in real time. The application of this distributed simulation facility to support a study of the effect of shared information (via air-ground datalink) on pilot/controller shared situation awareness and re-route negotiation is also presented.

  17. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

    PubMed

    Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-11-24

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal. PMID:26554014

  18. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope.

    PubMed

    Tsai, Shang-Yi A; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-Fei; Xi, Zheng-Xiong; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-11-24

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER-mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal.

  19. Sigma-1 receptor mediates cocaine-induced transcriptional regulation by recruiting chromatin-remodeling factors at the nuclear envelope

    PubMed Central

    Tsai, Shang-Yi A.; Chuang, Jian-Ying; Tsai, Meng-Shan; Wang, Xiao-fei; Hung, Jan-Jong; Chang, Wen-Chang; Bonci, Antonello; Su, Tsung-Ping

    2015-01-01

    The sigma-1 receptor (Sig-1R) chaperone at the endoplasmic reticulum (ER) plays important roles in cellular regulation. Here we found a new function of Sig-1R, in that it translocates from the ER to the nuclear envelope (NE) to recruit chromatin-remodeling molecules and regulate the gene transcription thereof. Sig-1Rs mainly reside at the ER–mitochondrion interface. However, on stimulation by agonists such as cocaine, Sig-1Rs translocate from ER to the NE, where Sig-1Rs bind NE protein emerin and recruit chromatin-remodeling molecules, including lamin A/C, barrier-to-autointegration factor (BAF), and histone deacetylase (HDAC), to form a complex with the gene repressor specific protein 3 (Sp3). Knockdown of Sig-1Rs attenuates the complex formation. Cocaine was found to suppress the gene expression of monoamine oxidase B (MAOB) in the brain of wild-type but not Sig-1R knockout mouse. A single dose of cocaine (20 mg/kg) in rats suppresses the level of MAOB at nuclear accumbens without affecting the level of dopamine transporter. Daily injections of cocaine in rats caused behavioral sensitization. Withdrawal from cocaine in cocaine-sensitized rats induced an apparent time-dependent rebound of the MAOB protein level to about 200% over control on day 14 after withdrawal. Treatment of cocaine-withdrawn rats with the MAOB inhibitor deprenyl completely alleviated the behavioral sensitization to cocaine. Our results demonstrate a role of Sig-1R in transcriptional regulation and suggest cocaine may work through this newly discovered genomic action to achieve its addictive action. Results also suggest the MAOB inhibitor deprenyl as a therapeutic agent to block certain actions of cocaine during withdrawal. PMID:26554014

  20. Source Term Estimation of Radioxenon Released from the Fukushima Dai-ichi Nuclear Reactors Using Measured Air Concentrations and Atmospheric Transport Modeling

    SciTech Connect

    Eslinger, Paul W.; Biegalski, S.; Bowyer, Ted W.; Cooper, Matthew W.; Haas, Derek A.; Hayes, James C.; Hoffman, Ian; Korpach, E.; Yi, Jing; Miley, Harry S.; Rishel, Jeremy P.; Ungar, R. Kurt; White, Brian; Woods, Vincent T.

    2014-01-01

    Systems designed to monitor airborne radionuclides released from underground nuclear explosions detected radioactive fallout from the Fukushima Daiichi nuclear accident in March 2011. Atmospheric transport modeling (ATM) of plumes of noble gases and particulates were performed soon after the accident to determine plausible detection locations of any radioactive releases to the atmosphere. We combine sampling data from multiple International Modeling System (IMS) locations in a new way to estimate the magnitude and time sequence of the releases. Dilution factors from the modeled plume at five different detection locations were combined with 57 atmospheric concentration measurements of 133-Xe taken from March 18 to March 23 to estimate the source term. This approach estimates that 59% of the 1.24×1019 Bq of 133-Xe present in the reactors at the time of the earthquake was released to the atmosphere over a three day period.