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Sample records for nuclear transport factors

  1. Nuclear transport factors: global regulation of mitosis.

    PubMed

    Forbes, Douglass J; Travesa, Anna; Nord, Matthew S; Bernis, Cyril

    2015-08-01

    The unexpected repurposing of nuclear transport proteins from their function in interphase to an equally vital and very different set of functions in mitosis was very surprising. The multi-talented cast when first revealed included the import receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a subset of nuclear pore proteins. In this review, we report that recent years have revealed new discoveries in each area of this expanding story in vertebrates: (a) The cast of nuclear import receptors playing a role in mitotic spindle regulation has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an export receptor, are involved in different aspects of spindle assembly. Importin beta and transportin also regulate nuclear envelope and pore assembly. (b) The role of nucleoporins has grown to include recruiting the key microtubule nucleator - the γ-TuRC complex - and the exportin Crm1 to the mitotic kinetochores of humans. Together they nucleate microtubule formation from the kinetochores toward the centrosomes. (c) New research finds that the original importin beta/RanGTP team have been further co-opted by evolution to help regulate other cellular and organismal activities, ranging from the actual positioning of the spindle within the cell perimeter, to regulation of a newly discovered spindle microtubule branching activity, to regulation of the interaction of microtubule structures with specific actin structures. (d) Lastly, because of the multitudinous roles of karyopherins throughout the cell cycle, a recent large push toward testing their potential as chemotherapeutic targets has begun to yield burgeoning progress in the clinic. PMID:25982429

  2. Reprint of "Nuclear transport factors: global regulation of mitosis".

    PubMed

    Forbes, Douglass J; Travesa, Anna; Nord, Matthew S; Bernis, Cyril

    2015-06-01

    The unexpected repurposing of nuclear transport proteins from their function in interphase to an equally vital and very different set of functions in mitosis was very surprising. The multi-talented cast when first revealed included the import receptors, importin alpha and beta, the small regulatory GTPase RanGTP, and a subset of nuclear pore proteins. In this review, we report that recent years have revealed new discoveries in each area of this expanding story in vertebrates: (a) The cast of nuclear import receptors playing a role in mitotic spindle regulation has expanded: both transportin, a nuclear import receptor, and Crm1/Xpo1, an export receptor, are involved in different aspects of spindle assembly. Importin beta and transportin also regulate nuclear envelope and pore assembly. (b) The role of nucleoporins has grown to include recruiting the key microtubule nucleator – the γ-TuRC complex – and the exportin Crm1 to the mitotic kinetochores of humans. Together they nucleate microtubule formation from the kinetochores toward the centrosomes. (c) New research finds that the original importin beta/RanGTP team have been further co-opted by evolution to help regulate other cellular and organismal activities, ranging from the actual positioning of the spindle within the cell perimeter, to regulation of a newly discovered spindle microtubule branching activity, to regulation of the interaction of microtubule structures with specific actin structures. (d) Lastly, because of the multitudinous roles of karyopherins throughout the cell cycle, a recent large push toward testing their potential as chemotherapeutic targets has begun to yield burgeoning progress in the clinic. PMID:26196321

  3. 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.

  4. 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).

  5. Hepatocyte nuclear factor-4alpha and bile acids regulate human concentrative nucleoside transporter-1 gene expression.

    PubMed

    Klein, Kerstin; Kullak-Ublick, Gerd A; Wagner, Martin; Trauner, Michael; Eloranta, Jyrki J

    2009-04-01

    The concentrative nucleoside transporter-1 (CNT1) is a member of the solute carrier 28 (SLC28) gene family and is expressed in the liver, intestine, and kidneys. CNT1 mediates the uptake of naturally occurring pyrimidine nucleosides, but also nucleoside analogs used in anticancer and antiviral therapy. Thus expression levels of CNT1 may affect the pharmacokinetics of these drugs and the outcome of drug therapy. Because little is known about the transcriptional regulation of human CNT1 gene expression, we have characterized the CNT1 promoter with respect to DNA response elements and their binding factors. The transcriptional start site of the CNT1 gene was determined by 5'-RACE. In silico analysis revealed the existence of three putative binding sites for the nuclear receptor hepatocyte nuclear factor-4alpha (HNF-4alpha) within the CNT1 promoter. A luciferase reporter gene construct containing the CNT1 promoter region was transactivated by HNF-4alpha in human cell lines derived from the liver, intestine, and kidneys. Consistent with this, we showed in electromobility shift assays that HNF-4alpha specifically binds to two conserved direct repeat-1 motifs within the proximal CNT1 promoter. In cotransfection experiments, the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha further increased, whereas the bile acid-inducible corepressor small heterodimer partner reduced, HNF-4alpha-dependent CNT1 promoter activity. Consistent with the latter phenomenon, CNT1 mRNA expression levels were suppressed in primary human hepatocytes upon bile acid treatment. Supporting the physiological relevance and species conservation of this effect, ileal Cnt1 mRNA expression was decreased upon bile acid feeding and increased upon bile duct ligation in mice. PMID:19228884

  6. Fasting Induces Nuclear Factor E2-Related Factor 2 and ATP-Binding Cassette Transporters via Protein Kinase A and Sirtuin-1 in Mouse and Human

    PubMed Central

    Kulkarni, Supriya R.; Donepudi, Ajay C.; Xu, Jialin; Wei, Wei; Cheng, Qiuqiong C.; Driscoll, Maureen V.; Johnson, Delinda A.; Johnson, Jeffrey A.; Li, Xiaoling

    2014-01-01

    Abstract Aims: The purpose of this study was to determine whether 3′-5′-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) and Sirtuin-1 (SIRT1) dependent mechanisms modulate ATP-binding Cassette (ABC) transport protein expression. ABC transport proteins (ABCC2–4) are essential for chemical elimination from hepatocytes and biliary excretion. Nuclear factor-E2 related-factor 2 (NRF2) is a transcription factor that mediates ABCC induction in response to chemical inducers and liver injury. However, a role for NRF2 in the regulation of transporter expression in nonchemical models of liver perturbation is largely undescribed. Results: Here we show that fasting increased NRF2 target gene expression through NRF2- and SIRT1–dependent mechanisms. In intact mouse liver, fasting induces NRF2 target gene expression by at least 1.5 to 5-fold. In mouse and human hepatocytes, treatment with 8-Bromoadenosine-cAMP, a cAMP analogue, increased NRF2 target gene expression and antioxidant response element activity, which was decreased by the PKA inhibitor, H-89. Moreover, fasting induced NRF2 target gene expression was decreased in liver and hepatocytes of SIRT1 liver-specific null mice and NRF2-null mice. Lastly, NRF2 and SIRT1 were recruited to MAREs and Antioxidant Response Elements (AREs) in the human ABCC2 promoter. Innovation: Oxidative stress mediated NRF2 activation is well described, yet the influence of basic metabolic processes on NRF2 activation is just emerging. Conclusion: The current data point toward a novel role of nutrient status in regulation of NRF2 activity and the antioxidant response, and indicates that cAMP/PKA and SIRT1 are upstream regulators for fasting-induced activation of the NRF2-ARE pathway. Antioxid. Redox Signal. 20, 15–30. PMID:23725046

  7. Nuclear factor-κB regulates the expression of multiple genes encoding liver transport proteins.

    PubMed

    Balasubramaniyan, Natarajan; Ananthanarayanan, Meenakshisundaram; Suchy, Frederick J

    2016-04-15

    In this study we identified the mechanisms underlying the inhibitory effects of NF-κB on the expression of genes encoding multiple liver transport proteins. Well-conserved NF-κB binding sites were found in the promoters of farnesoid X receptor (FXR)-target genes. An electromobility shift assay (EMSA) demonstrated the specific interaction between the NF-κB p65 protein and a (32)P-labeled BSEP NF-κB response element (NF-κBE). Chromatin immunoprecipitation (ChIP) analysis confirmed binding of NF-κB p65 to the BSEP locus but not the FXRE in vitro. NF-κB p65 overexpression in Huh-7 cells markedly repressed FXR/RXR transactivation of the BSEP, ABCG5/G8, MRP2, and FXR promoters, which was totally reversed by expression of the IκBα super-repressor. NF-κB interacted directly with FXR on coimmunoprecipitation, suggesting another level for the inhibitory effects of NF-κB on FXR-target genes. In vivo ChIP analysis with liver nuclei obtained from mice after 3 days of common bile duct ligation (BDL) or 6 h post-lipopolysaccharide (LPS) injection showed a markedly increased recruitment of NF-κB p65 to the Bsep promoter compared with controls. There was also increased recruitment of the corepressor silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) and histone deacetylase (HDAC)3 and HDAC2 to the NF-κB sites. We also found that NF-κB p65 was recruited to NF-κB binding sites in the promoters of organic solute transporter, OSTα and OSTβ, and unexpectedly activated rather than repressed gene expression. In mouse liver after BDL NF-κB recruitment to Ostα and Ostβ promoters was associated with increased binding of the potent coactivator cAMP response element binding protein (CREB)-binding protein (CBP)/p300 to the NF-κBE and depletion of CBP/p300 at the FXR element. Overall, these studies demonstrate a novel role for NF-κB in adaptation to obstructive and LPS-induced cholestasis acting through recruitment to specific NF-κB binding sites in

  8. Alterations in hepatic mRNA expression of phase II enzymes and xenobiotic transporters after targeted disruption of hepatocyte nuclear factor 4 alpha.

    PubMed

    Lu, Hong; Gonzalez, Frank J; Klaassen, Curtis

    2010-12-01

    Hepatocyte nuclear factor 4 alpha (HNF4a) is a liver-enriched master regulator of liver function. HNF4a is important in regulating hepatic expression of certain cytochrome P450s. The purpose of this study was to use mice lacking HNF4a expression in liver (HNF4a-HNull) to elucidate the role of HNF4a in regulating hepatic expression of phase II enzymes and transporters in mice. Compared with male wild-type mice, HNF4a-HNull male mouse livers had (1) markedly lower messenger RNAs (mRNAs) encoding the uptake transporters sodium taurocholate cotransporting polypeptide, organic anion transporting polypeptide (Oatp) 1a1, Oatp2b1, organic anion transporter 2, sodium phosphate cotransporter type 1, sulfate anion transporter 1, sodium-dependent vitamin C transporter 1, the phase II enzymes Uridine 5'-diphospho (UDP)-glucuronosyltransferase (Ugt) 2a3, Ugt2b1, Ugt3a1, Ugt3a2, sulfotransferase (Sult) 1a1, Sult1b1, Sult5a1, the efflux transporters multidrug resistance-associated protein (Mrp) 6, and multidrug and toxin extrusion 1; (2) moderately lower mRNAs encoding Oatp1b2, organic cation transporter (Oct) 1, Ugt1a5, Ugt1a9, glutathione S-transferase (Gst) m4, Gstm6, and breast cancer resistance protein; but (3) higher mRNAs encoding Oatp1a4, Octn2, Ugt1a1, Sult1e1, Sult2a2, Gsta4, Gstm1-m3, multidrug resistance protein (Mdr) 1a, Mrp3, and Mrp4. Hepatic signaling of nuclear factor E2-related factor 2 and pregnane X receptor appear to be activated in HNF4a-HNull mice. In conclusion, HNF4a deficiency markedly alters hepatic mRNA expression of a large number of phase II enzymes and transporters, probably because of the loss of HNF4a, which is a transactivator and a determinant of gender-specific expression and/or adaptive activation of signaling pathways important in hepatic regulation of these phase II enzymes and transporters. PMID:20935164

  9. Constitutive Activation of Nuclear Factor-E2-Related Factor 2 Induces Biotransformation Enzyme and Transporter Expression in Livers of Mice With Hepatocyte-Specific Deletion of Kelch-like ECH-associated protein 1

    PubMed Central

    Cheng, Qiuqiong; Taguchi, Keiko; Aleksunes, Lauren M.; Manautou, José E.; Cherrington, Nathan J.; Yamamoto, Masayuki; Slitt, Angela L.

    2013-01-01

    Chemicals that activate nuclear factor-E2-related factor-2 (Nrf2) often increase multidrug resistance-associated protein expression in liver. Hepatocyte-specific deletion of Kelch-like ECH-associated protein 1 (Keap1) activates Nrf2. Use of hepatocyte-specific Keap1 deletion represents a non-pharmacological method to determine whether constitutive Nrf2 activation upregulates liver transporter expression in vivo. The mRNA, protein expression and localization of several biotransformation and transporters was determined in livers of wild-type and hepatocyte-specific Keap1-null mice. Sulfotransferase 2a1/2, NADP(H):quinone oxidoreductase 1, Cytochrome P450 2b10, 3a11, and glutamate-cysteine ligase catalytic subunit expression was increased in livers of Keap1-null mice. Oatp1a1 expression was nearly abolished, as compared to that detected in livers of wild-type mice. By contrast, Mrp 1-5 mRNA and protein levels were increased in Keap1-null mouse livers, with Mrp4 expression being more than 15-fold higher than wild-types. In summary, Nrf2 has a significant role in affecting expression of Oatp and Mrp expression. PMID:21538727

  10. Elliptic flow and nuclear modification factor in ultrarelativistic heavy-ion collisions within a partonic transport model.

    PubMed

    Uphoff, Jan; Senzel, Florian; Fochler, Oliver; Wesp, Christian; Xu, Zhe; Greiner, Carsten

    2015-03-20

    The quark gluon plasma produced in ultrarelativistic heavy-ion collisions exhibits remarkable features. It behaves like a nearly perfect liquid with a small shear viscosity to entropy density ratio and leads to the quenching of highly energetic particles. We show that both effects can be understood for the first time within one common framework. Employing the parton cascade Boltzmann approach to multiparton scatterings, the microscopic interactions and the space-time evolution of the quark gluon plasma are calculated by solving the relativistic Boltzmann equation. Based on cross sections obtained from perturbative QCD with explicitly taking the running coupling into account, we calculate the nuclear modification factor and elliptic flow in ultrarelativistic heavy-ion collisions. With only one single parameter associated with coherence effects of medium-induced gluon radiation, the experimental data of both observables can be understood on a microscopic level. Furthermore, we show that perturbative QCD interactions with a running coupling lead to a sufficiently small shear viscosity to entropy density ratio of the quark gluon plasma, which provides a microscopic explanation for the observations stated by hydrodynamic calculations. PMID:25839262

  11. 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

  12. 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. PMID:25892691

  13. Hypoxia-inducible factor-1α upregulates tyrosine hydroxylase and dopamine transporter by nuclear receptor ERRγ in SH-SY5Y cells.

    PubMed

    Lim, Juhee; Kim, Hyo-In; Bang, Yeojin; Seol, Wongi; Choi, Hueng-Sik; Choi, Hyun Jin

    2015-04-15

    Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor relevant to the development of many mammalian organs including the brain. However, the molecular mechanisms by which signaling events mediate neuronal differentiation have not been fully elucidated. In the present study, we show for the first time that the orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated by HIF-1α and plays essential roles in HIF-1α-induced upregulation of dopaminergic marker molecules such as tyrosine hydroxylase and dopamine transporter. We found that deferoxamine upregulated HIF-1α and enhanced the dopaminergic phenotype and neurite outgrowth of SH-SY5Y cells. Deferoxamine activated transcription and protein expression of ERRγ, and deferoxamine-induced upregulation of tyrosine hydroxylase and dopamine transporter was attenuated by using the ERRγ inverse agonist or silencing ERRγ. Altogether, these results suggest that HIF-1α can positively regulate the dopaminergic phenotype through ERRγ. This study could provide new perspectives for understanding the mechanisms underlying the promotion of dopaminergic neuronal differentiation by hypoxia. PMID:25807177

  14. 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

  15. 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

    O'Brien, Valerie P; Bokelmann, Kristin; Ramírez, Jacqueline; Jobst, Karoline; Ratain, Mark J; Brockmöller, Jürgen; Tzvetkov, Mladen V

    2013-10-01

    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

  16. 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

  17. 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

  18. 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

  19. Karyopherins in nuclear transport of homeodomain proteins during development

    PubMed Central

    Ye, Wenduo; Lin, Wenbo; Tartakoff, Alan M.; Tao, Tao

    2013-01-01

    Homeodomain proteins are crucial transcription factors for cell differentiation, cell proliferation and organ development. Interestingly, their homeodomain signature structure is important for both their DNA-binding and their nucleocytoplasmic trafficking. The accurate nucleocytoplasmic distribution of these proteins is essential for their functions. We summarize information on a) the roles of karyopherins for import and export of homeoproteins, b) the regulation of their nuclear transport during development, and c) the corresponding complexity of homeoprotein nucleocytoplasmic transport signals. PMID:21256166

  20. 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.

  1. Regulation of nuclear transport in proliferating and quiescent cells.

    PubMed

    Feldherr, C M; Akin, D

    1993-03-01

    Previously, we compared signal-mediated nuclear transport in proliferating and quiescent BALB/c 3T3 cells and found that both the relative rate of nuclear uptake and the functional size of the transport channels were significantly greater in proliferating cells. In this study, the possible causes of these permeability differences were investigated. To determine if the decrease in transport capacity in quiescent cells was due to a reduction in the availability of soluble cytoplasmic factors (i.e., ATP or receptors for nuclear location sequences), or changes in the properties of the pores themselves, proliferating and quiescent cells were fused, and nuclear import of nucleoplasmin-coated gold (NP-gold) particles was assayed in the heterokaryons 50-60 min later. Significant differences in nuclear uptake were maintained following fusion, even though the two nuclei shared a common cytoplasm, consistent with the view that permeability is regulated at the level of the pores. Cell shape also influenced signal-mediated nuclear import. This was demonstrated by studying transport in rounded and flattened cells attached to different-size palladium domains that were deposited on a nonadhesive substrate. Based on analysis of the nuclear uptake rates of large (110-270 A in diameter) and small (50-80 A in diameter) coated gold particles, it was determined that the functional size of the pores was significantly greater in flattened cells. The effect of growth factors on recovery of nuclear transport capacity following serum depletion was also analyzed. Partial recovery was achieved by treating cells with physiological concentrations of EGF, IGF-1, or PDGF; however, complete recovery required both EGF and IGF-1. PMID:8453991

  2. In or out? Regulating nuclear transport.

    PubMed

    Hood, J K; Silver, P A

    1999-04-01

    The compartmentalization of proteins within the nucleus or cytoplasm of a eukaryotic cell offers opportunity for regulation of cell cycle progression and signalling pathways. Nuclear localization of proteins is determined by their ability to interact with specific nuclear import and export factors. In the past year, substrate phosphorylation has emerged as a common mechanism for controlling this interaction. PMID:10209150

  3. 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. PMID:26894898

  4. 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…

  5. Air Transport of Spent Nuclear Fuel (SNF) Assemblies

    SciTech Connect

    Haire, M.J.; Moses, S.D.; Shapovalov, V.I.; Morenko, A.

    2007-07-01

    Sometimes the only feasible means of shipping research reactor spent nuclear fuel (SNF) among countries is via air transport because of location or political conditions. The International Atomic Energy Agency (IAEA) has established a regulatory framework to certify air transport Type C casks. However, no such cask has been designed, built, tested, and certified. In lieu of an air transport cask, research reactor SNF has been transported using a Type B cask under an exemption with special arrangements for administrative and security controls. This work indicates that it may be feasible to transport commercial power reactor SNF assemblies via air, and that the cost is only about three times that of shipping it by railway. Optimization (i.e., reduction) of this cost factor has yet to be done. (authors)

  6. 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…

  7. Analytic parametrization for nuclear form factors

    SciTech Connect

    Atkin, G.; Dumbrajs, O.

    1982-08-01

    A new analytic parametrization of the nuclear form factor is developed using a factorization theorem. We show that the nuclear form factor can be represented in terms of its real zeros and its asymptotic behavior. The parametrization is applied to nuclear form factor data of /sup 3/He and /sup 4/He. Our results suggest that further diffraction minima can be expected at higher momentum transfer where experiments have not yet been made.

  8. 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.

  9. Transport description of damped nuclear reactions

    SciTech Connect

    Randrup, J.

    1983-04-01

    Part I is an elementary introduction to the general transport theory of nuclear dynamics. It can be read without any special knowledge of the field, although basic quantum mechanics is required for the formal derivation of the general expression for the transport coefficients. The results can also be used in a wider context than the present one. Part II gives the student an up-to-date orientation about recent progress in the understanding of the angular-momentum variables in damped reactions. The emphasis is here on the qualitative understanding of the physics rather than the, at times somewhat tedious, formal derivations. (WHK)

  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. Nevada commercial spent nuclear fuel transportation experience

    SciTech Connect

    1991-09-01

    The purpose of this report is to present an historic overview of commercial reactor spent nuclear fuel (SNF) shipments that have occurred in the state of Nevada, and to review the accident and incident experience for this type of shipments. Results show that between 1964 and 1990, 309 truck shipments covering approximately 40,000 miles moved through Nevada; this level of activity places Nevada tenth among the states in the number of truck shipments of SNF. For the same period, 15 rail shipments moving through the State covered approximately 6,500 miles, making Nevada 20th among the states in terms of number of rail shipments. None of these shipments had an accident or an incident associated with them. Because the data for Nevada are so limited, national data on SNF transportation and the safety of truck and rail transportation in general were also assessed.

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. 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.

  17. Managing Free-energy Barriers in Nuclear Pore Transport

    PubMed Central

    Nielsen, Brian; Jeppesen, Claus

    2006-01-01

    The Nuclear Pore Complexes (NPC) facilitate highly selective gateways for transport of macromolecules across the Nuclear Envelope (NE). Based on the current accumulated knowledge of the architecture of NPC we have established a minimal physical model of the pore and the transport mechanism. The barrier properties of the NPC model are analyzed by the recently established Wang–Landau Monte Carlo computer simulation technique and the transport properties are extracted by employing Kramers’ theory of reaction rates. We show that our physical model can account for a range of characteristics observed for nuclear pore transport. PMID:19669451

  18. Estimated consequences from severe spent nuclear fuel transportation accidents

    SciTech Connect

    Arnish, J.J.; Monette, F.; LePoire, D.; Biwer, B.M.

    1996-06-01

    The RISKIND software package is used to estimate radiological consequences of severe accident scenarios involving the transportation of spent nuclear fuel. Radiological risks are estimated for both a collective population and a maximally exposed individual based on representative truck and rail cask designs described in the U.S. Nuclear Regulatory Commission (NRC) modal study. The estimate of collective population risk considers all possible environmental pathways, including acute and long-term exposures, and is presented in terms of the 50-y committed effective dose equivalent. Radiological risks to a maximally exposed individual from acute exposure are estimated and presented in terms of the first year and 50-y committed effective dose equivalent. Consequences are estimated for accidents occurring in rural and urban population areas. The modeled pathways include inhalation during initial passing of the radioactive cloud, external exposure from a reduction of the cask shielding, long-term external exposure. from ground deposition, and ingestion from contaminated food (rural only). The major pathways and contributing radionuclides are identified, and the effects of possible mitigative actions are discussed. The cask accident responses and the radionuclide release fractions are modeled as described in the NRC modal study. Estimates of severe accident probabilities are presented for both truck and rail modes of transport. The assumptions made in this study tend to be conservative; however, a set of multiplicative factors are identified that can be applied to estimate more realistic conditions.

  19. 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.

  20. Enzymatically Driven Transport: A Kinetic Theory for Nuclear Export

    PubMed Central

    Kim, Sanghyun; Elbaum, M.

    2013-01-01

    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. PMID:24209844

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Risk management of onsite transportation of nuclear waste

    SciTech Connect

    Field, J.G.; Wang, O.S.; Mercado, J.E.

    1993-03-01

    The United States Department of Energy (DOE) Hanford Site recently has undergone a significant change in mission. The focus of operations has shifted from plutonium production to environmental restoration. This transition has caused a substantial increase in quantities of nuclear waste and other hazardous materials packaged and transported onsite. In response to the escalating transportation activity, Westinghouse Hanford Company (Westinghouse Hanford), the Hanford Site operations and engineering contractor, is proposing an integrated risk assessment methodology and risk management strategy to enhance the safety of onsite packaging and transportation operations involving nuclear waste. The proposed methodology consists of three integral parts: risk assessment, risk acceptance criteria, and risk minimization. The purpose of the methodology is to ensure that the risk for each ongoing transportation activity is acceptable and to minimize the overall risk for current and future onsite operations.

  9. 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.

  10. Molecular geometric phase from the exact electron-nuclear factorization

    NASA Astrophysics Data System (ADS)

    Requist, Ryan; Tandetzky, Falk; Gross, E. K. U.

    2016-04-01

    The Born-Oppenheimer electronic wave function ΦRBO(r ) picks up a topological phase factor ±1 , a special case of Berry phase, when it is transported around a conical intersection of two adiabatic potential energy surfaces in R space. We show that this topological quantity reverts to a geometric quantity ei γ if the geometric phase γ =∮Im <ΦR|∇μΦR> .d Rμ is evaluated with the conditional electronic wave function ΦR(r ) from the exact electron-nuclear factorization ΦR(r ) χ (R ) instead of the adiabatic function ΦRBO(r ) . A model of a pseudorotating triatomic molecule, also applicable to dynamical Jahn-Teller ions in bulk crystals, provides examples of nontrivial induced vector potentials and molecular geometric phase from the exact factorization. The induced vector potential gives a contribution to the circulating nuclear current that cannot be removed by a gauge transformation. The exact potential energy surface is calculated and found to contain a term depending on the Fubini-Study metric for the conditional electronic wave function.

  11. 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.

  12. 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.

  13. 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.

  14. Importin alpha: a multipurpose nuclear-transport receptor.

    PubMed

    Goldfarb, David S; Corbett, Anita H; Mason, D Adam; Harreman, Michelle T; Adam, Stephen A

    2004-09-01

    The importin alpha/beta heterodimer targets hundreds of proteins to the nuclear-pore complex (NPC) and facilitates their translocation across the nuclear envelope. Importin alpha binds to classical nuclear localization signal (cNLS)-containing proteins and links them to importin beta, the karyopherin that ferries the ternary complex through the NPC. A second karyopherin, the exportin CAS, recycles importin alpha back to the cytoplasm. In this article, we discuss control mechanisms that importin alpha exerts over the assembly and disassembly of the ternary complex and we describe how new groups of importin alpha genes arose during the evolution of metazoan animals to function in development and differentiation. We also describe activities of importin alpha that seem to be distinct from its housekeeping functions in nuclear transport. PMID:15350979

  15. Safety analysis of irradiated nuclear fuel transportation container

    SciTech Connect

    Uspuras, E.; Rimkevicius, S.

    2007-07-01

    Ignalina NPP comprises two Units with RBMK-1500 reactors. After the Unit 1 of the Ignalina Nuclear Power Plant was shut down in 2004, approximately 1000 fuel assemblies from Unit were available for further reuse in Unit 2. The fuel-transportation container, vehicle, protection shaft and other necessary equipment were designed in order to implement the process for on-site transportation of Unit 1 fuel for reuse in the Unit 2. The Safety Analysis Report (SAR) was developed to demonstrate that the proposed set of equipment performs all functions and assures the required level of safety for both normal operation and accident conditions. The purpose of this paper is to introduce the content and main results of SAR, focusing attention on the container used to transport spent fuel assemblies from Unit I on Unit 2. In the SAR, the structural integrity, thermal, radiological and nuclear safety calculations are performed to assess the acceptance of the proposed set of equipment. The safety analysis demonstrated that the proposed nuclear fuel transportation container and other equipment are in compliance with functional, design and regulatory requirements and assure the required safety level. (authors)

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis

    PubMed Central

    Yang, Zhong-Fa; Drumea, Karen; Mott, Stephanie; Wang, Junling

    2014-01-01

    Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) to examine the role of Gabp in mitochondrial biogenesis, function, and gene expression. Gabpα loss modestly reduced mitochondrial mass, ATP production, oxygen consumption, and mitochondrial protein synthesis but did not alter mitochondrial morphology, membrane potential, apoptosis, or the expression of several genes that were previously reported to be GABP targets. However, the expression of Tfb1m, a methyltransferase that modifies ribosomal rRNA and is required for mitochondrial protein translation, was markedly reduced in Gabpα-null MEFs. We conclude that Gabp regulates Tfb1m expression and plays an essential, nonredundant role in mitochondrial biogenesis. PMID:24958105

  2. 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

  3. 48 CFR 247.372 - DD Form 1654, Evaluation of Transportation Cost Factors.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... of Transportation Cost Factors. 247.372 Section 247.372 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT OF DEFENSE CONTRACT MANAGEMENT TRANSPORTATION Transportation in Supply Contracts 247.372 DD Form 1654, Evaluation of Transportation Cost Factors....

  4. 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.

  5. 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.

  6. Importin α: a key molecule in nuclear transport and non-transport functions.

    PubMed

    Miyamoto, Yoichi; Yamada, Kohji; Yoneda, Yoshihiro

    2016-08-01

    Importin α performs the indispensable role of ferrying proteins from the cytoplasm into the nucleus with a transport carrier, importin β1. Mammalian cells from mouse or human contain either six or seven importin α subtypes, respectively, each with a tightly regulated expression. Therefore, the combination of subtype expression in a cell defines distinct signaling pathways to achieve progressive changes in gene expression essential for cellular events, such as differentiation. Recent studies reveal that, in addition to nucleocytoplasmic transport, importin αs also serve non-transport functions. In this review, we first discuss the physiological significance of importin α as a nuclear transport regulator, and then focus on the functional diversities of importin αs based on their specific subcellular and cellular localizations, such as the nucleus and plasma membrane. These findings enrich our knowledge of how importin αs actively contribute to various cellular events. PMID:27289017

  7. Classic nuclear localization signals and a novel nuclear localization motif are required for nuclear transport of porcine parvovirus capsid proteins.

    PubMed

    Boisvert, Maude; Bouchard-Lévesque, Véronique; Fernandes, Sandra; Tijssen, Peter

    2014-10-01

    Nuclear targeting of capsid proteins (VPs) is important for genome delivery and precedes assembly in the replication cycle of porcine parvovirus (PPV). Clusters of basic amino acids, corresponding to potential nuclear localization signals (NLS), were found only in the unique region of VP1 (VP1up, for VP1 unique part). Of the five identified basic regions (BR), three were important for nuclear localization of VP1up: BR1 was a classic Pat7 NLS, and the combination of BR4 and BR5 was a classic bipartite NLS. These NLS were essential for viral replication. VP2, the major capsid protein, lacked these NLS and contained no region with more than two basic amino acids in proximity. However, three regions of basic clusters were identified in the folded protein, assembled into a trimeric structure. Mutagenesis experiments showed that only one of these three regions was involved in VP2 transport to the nucleus. This structural NLS, termed the nuclear localization motif (NLM), is located inside the assembled capsid and thus can be used to transport trimers to the nucleus in late steps of infection but not for virions in initial infection steps. The two NLS of VP1up are located in the N-terminal part of the protein, externalized from the capsid during endosomal transit, exposing them for nuclear targeting during early steps of infection. Globally, the determinants of nuclear transport of structural proteins of PPV were different from those of closely related parvoviruses. Importance: Most DNA viruses use the nucleus for their replication cycle. Thus, structural proteins need to be targeted to this cellular compartment at two distinct steps of the infection: in early steps to deliver viral genomes to the nucleus and in late steps to assemble new viruses. Nuclear targeting of proteins depends on the recognition of a stretch of basic amino acids by cellular transport proteins. This study reports the identification of two classic nuclear localization signals in the minor capsid

  8. Characterization of nuclear targeting signal of hepatitis delta antigen: nuclear transport as a protein complex.

    PubMed Central

    Xia, Y P; Yeh, C T; Ou, J H; Lai, M M

    1992-01-01

    Hepatitis delta antigen (HDAg) is the only protein encoded by hepatitis delta virus (HDV). HDAg has been demonstrated in the nuclei of HDV-infected hepatocytes, and its nuclear transport may be important for the replication of HDV RNA. In this report, we investigated the mechanism of nuclear transport of HDAg. By expressing fusion proteins consisting of the different portions of HDAg and alpha-globin, we have identified a nuclear localization signal (NLS) within the N-terminal one-third of HDAg. It consists of two stretches of basic amino acid domains separated by a short run of nonbasic amino acids. Both of the basic domains are necessary for the efficient nuclear transport of HDAg. The nonbasic spacer amino acids could be removed without affecting the nuclear targeting of HDAg significantly. Thus, the HDAg NLS belongs to a newly identified class of NLS which consists of two discontiguous stretches of basic amino acids. This NLS is separated from a stretch of steroid receptor NLS-like sequence, which is also present but not functioning as an NLS, in HDAg. Furthermore, we have shown that subfragments of HDAg which do not contain the NLS can be passively transported into the nucleus by a trans-acting full-length HDAg, provided that these subfragments contain the region with a leucine zipper sequence. Thus, our results indicate that HDAg forms aggregates in the cytoplasm and that the HDAg oligomerization is probably mediated by the leucine zipper sequence. Therefore, HDAg is likely transported into the nucleus as a protein complex. Images PMID:1731113

  9. 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

  10. Function of steroidogenic factor 1 domains in nuclear localization, transactivation, and interaction with transcription factor TFIIB and c-Jun.

    PubMed

    Li, L A; Chiang, E F; Chen, J C; Hsu, N C; Chen, Y J; Chung, B C

    1999-09-01

    Normal endocrine development and function require nuclear hormone receptor SF-1 (steroidogenic factor 1). To understand the molecular mechanism of SF-1 action, we have investigated its domain function by mutagenesis and functional analyses. Our mutant studies show that the putative AF2 (activation function 2) helix located at the C-terminal end is indispensable for gene activation. SF-1 does not have an N-terminal AF1 domain. Instead, it contains a unique FP region, composed of the Ftz-F1 box and the proline cluster, after the zinc finger motif. The FP region interacts with transcription factor IIB (TFIIB) in vitro. This interaction requires residues 178-201 of TFIIB, a domain capable of binding several transcription factors. The FP region also mediates physical interaction with c-Jun, and this interaction greatly enhances SF-1 activity. The putative SF-1 ligand, 25-hydroxycholesterol, has no effects on these bindings. In addition, the Ftz-F1 box contains a bipartite nuclear localization signal (NLS). Removing the basic residues at either end of the key nuclear localization sequence NLS2.2 abolishes the nuclear transport. Expression of mutants containing only the FP region or lacking the AF2 domain blocks wild-type SF-1 activity in cells. By contrast, the mutant having a truncated nuclear localization signal lacks this dominant negative effect. These results delineate the importance of the FP and AF2 regions in nuclear localization, protein-protein interaction, and transcriptional activation. PMID:10478848

  11. 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.

  12. A strain-dependent diffusivity model to study the nuclear import of mechanobiological transcription factors.

    PubMed

    Nava, Michele M; Fedele, Roberto; Raimondi, Manuela T

    2015-08-01

    Nuclear spreading plays a crucial role in stem cell fate determination. In previous works, we reported evidence of multipotency maintenance of mesenchymal stromal cells cultured on three-dimensional engineered niche substrates fabricated via two-photon laser polymerization (2PP). We correlated multipotency maintenance to a more roundish nuclear morphology of cells cultured in the 2PP-fabricated niches, with respect to those on flat substrates. To interpret these findings, here we present a multiphysics model coupling nuclear strains induced by cell adhesion to diffusive transport across the cell nucleus. We reconstructed the cell nuclear geometry from confocal Z-stack images of 2PP-cultured cells, and we estimated the volume, surface and shape factors. The levels of nuclear spreading significantly varied depending on the cell localization within the niche architecture. We assumed the cell diffusivity as a function of the local volumetric strain. The computational model also indicate that the larger the nuclear deformation (e.g. in spread nuclei), the higher the nuclear flux of small solutes such as transcription factors through the nuclear membrane. Our results point towards nuclear deformation as a primary mechanism by which the stem cell translates its shape into a fate decision, i.e. through a strain-dependent amplification of the diffusive flow of signaling molecules into the nucleus. PMID:26736643

  13. 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

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

    PubMed

    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

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. Role of zinc finger structure in nuclear localization of transcription factor Sp1

    SciTech Connect

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

    2009-02-27

    Transcription factor Sp1 is localized in the nucleus and regulates gene expression. Our previous study demonstrated that the carboxyl terminal region of Sp1 containing 3-zinc finger region as DNA binding domain can also serve as nuclear localization signal (NLS). However, the nuclear transport mechanism of Sp1 has not been well understood. In this study, we performed a gene expression study on mutant Sp1 genes causing a set of amino acid substitutions in zinc finger domains to elucidate nuclear import activity. Nuclear localization of the GFP-fused mutant Sp1 proteins bearing concomitant substitutions in the first and third zinc fingers was highly inhibited. These mutant Sp1 proteins had also lost the binding ability as to the GC box sequence. The results suggest that the overall tertiary structure formed by the three zinc fingers is essential for nuclear localization of Sp1 as well as dispersed basic amino acids within the zinc fingers region.

  3. 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

  4. 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.

  5. Vehicle emission unit risk factors for transportation risk assessments

    SciTech Connect

    Biwer, B.M.; Butler, J.P.

    1999-12-01

    When the transportation risk posed by shipments of hazardous chemical and radioactive materials is being assessed, it is necessary to evaluate the risks associated with both vehicle emissions and cargo-related risks. Diesel exhaust and fugitive dust emissions from vehicles transporting hazardous shipments lead to increased air pollution, which increases the risk of latent fatalities in the affected population along the transport route. The estimated risk from these vehicle-related sources can often by as large or larger than the estimated risk associated with the material being transported. In this paper, data from the US Environmental Protection Agency's Motor Vehicle-Related Air Toxics Study are first used to develop latent cancer fatality estimates per kilometer of travel in rural and urban areas for all diesel truck classes. These unit risk factors are based on studies investigating the carcinogenic nature of diesel exhaust. With the same methodology, the current per=kilometer latent fatality risk factor used in transportation risk assessment for heavy diesel trucks in urban areas is revised and the analysis expanded to provide risk factors for rural areas and all diesel truck classes. These latter fatality estimates may include, but are not limited to, cancer fatalities and are based primarily on the most recent epidemiological data available on mortality rates associated with ambient air PM-10 concentrations.

  6. Vehicle emission unit risk factors for transportation risk assessments.

    PubMed

    Biwer, B M; Butler, J P

    1999-12-01

    When the transportation risk posed by shipments of hazardous chemical and radioactive materials is being assessed, it is necessary to evaluate the risks associated with both vehicle emissions and cargo-related risks. Diesel exhaust and fugitive dust emissions from vehicles transporting hazardous shipments lead to increased air pollution, which increases the risk of latent fatalities in the affected population along the transport route. The estimated risk from these vehicle-related sources can often be as large or larger than the estimated risk associated with the material being transported. In this paper, data from the U.S. Environmental Protection Agency's Motor Vehicle-Related Air Toxics Study are first used to develop latent cancer fatality estimates per kilometer of travel in rural and urban areas for all diesel truck classes. These unit risk factors are based on studies investigating the carcinogenic nature of diesel exhaust. With the same methodology, the current per-kilometer latent fatality risk factor used in transportation risk assessments for heavy diesel trucks in urban areas is revised and the analysis expanded to provide risk factors for rural areas and all diesel truck classes. These latter fatality estimates may include, but are not limited to, cancer fatalities and are based primarily on the most recent epidemiological data available on mortality rates associated with ambient air PM-10 concentrations. PMID:10765454

  7. 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.

  8. Operational considerations for a crewed nuclear powered space transportation vehicle

    NASA Astrophysics Data System (ADS)

    Borrer, Jerry L.; Hoffman, Stephen J.

    1993-01-01

    Applying nuclear propulsion technology to human space travel will require new approaches to conducting human operations in space. Due to the remoteness of these types of missions, the crew and their vehicle must be capable of operating independent from Earth-based support. This paper discusses current operational studies which address methods for performing these types of remote and autonomous missions. Methods of managing the hazards to humans who will operate these high-energy nuclear-powered transportation vehicles also is reviewed. Crew training for both normal and contingency operations is considered. Options are evaluated on how best to train crews to operate and maintain the systems associated with a nuclear engine. Methods of maintaining crew proficiency during the long months of space travel are discussed. Vehicle health maintenance also will be a primary concern during these long missions. A discussion is presented on how on-board vehicle health maintenance systems will monitor system trends, identified system weaknesses, and either isolate critical failures or provide the crew with adequate warning of impending problems.

  9. 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

  10. Factors influencing chemical durability of nuclear waste glasses

    SciTech Connect

    Feng, Xiangdong; Bates, J.K.

    1993-03-01

    A short summary is given of our studies on the major factors that affect the chemical durability of nuclear waste glasses. These factors include glass composition, solution composition, SA/V (ratio of glass surface area to the volume of solution), radiation, and colloidal formation. These investigations have enabled us to gain a better understanding of the chemical durability of nuclear waste glasses and to accumulate.a data base for modeling the long-term durability of waste glass, which will be used in the risk assessment of nuclear waste disposal. This knowledge gained also enhances our ability to formulate optimal waste glass compositions.

  11. Factors influencing chemical durability of nuclear waste glasses

    SciTech Connect

    Feng, Xiangdong; Bates, J.K.

    1993-01-01

    A short summary is given of our studies on the major factors that affect the chemical durability of nuclear waste glasses. These factors include glass composition, solution composition, SA/V (ratio of glass surface area to the volume of solution), radiation, and colloidal formation. These investigations have enabled us to gain a better understanding of the chemical durability of nuclear waste glasses and to accumulate.a data base for modeling the long-term durability of waste glass, which will be used in the risk assessment of nuclear waste disposal. This knowledge gained also enhances our ability to formulate optimal waste glass compositions.

  12. 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)

  13. 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.

  14. 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.

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

    PubMed Central

    Dang, Van-Dinh; Levin, Henry L.

    2000-01-01

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

  16. Nuclear transport of galectin-3 and its therapeutic implications

    PubMed Central

    Funasaka, Tatsuyoshi; Raz, Avraham; Nangia-Makker, Pratima

    2014-01-01

    Galectin-3, a member of β-galactoside-binding gene family is a multi-functional protein, which regulates pleiotropic biological functions such as cell growth, cell adhesion, cell-cell interactions, apoptosis, angiogenesis and mRNA processing. Its unique structure enables it to interact with a plethora of ligands in a carbohydrate dependent or independent manner. Galectin-3 is mainly a cytosolic protein, but can easily traverse the intracellular and plasma membranes to translocate into the nucleus, mitochondria or get externalized. Depending on the cell type, specific experimental conditions in vitro, cancer type and stage, galectin-3 has been reported to be exclusively cytoplasmic, predominantly nuclear or distributed between the two compartments. In this review we have summarized the dynamics of galectin-3 shuttling between the nucleus and the cytoplasm, the nuclear transport mechanisms of galectin-3, how its specific interactions with the members of β-catenin signaling pathways affect tumor progression, and its implications as a therapeutic target. PMID:24657939

  17. 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.

  18. 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

  19. 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

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

    DOE PAGESBeta

    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

  1. 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.

  2. 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.

  3. Nuclear fragmentation database for GCR transport code development

    NASA Astrophysics Data System (ADS)

    Zeitlin, C.; Guetersloh, S.; Heilbronn, L.; Miller, J.; Fukumura, A.; Iwata, Y.; Murakami, T.; Sihver, L.

    2010-09-01

    A critical need for NASA is the ability to accurately model the transport of heavy ions in the Galactic Cosmic Rays (GCR) through matter, including spacecraft walls, equipment racks, etc. Nuclear interactions are of great importance in the GCR transport problem, as they can cause fragmentation of the incoming ion into lighter ions. Since the radiation dose delivered by a particle is proportional to the square of (charge/velocity), fragmentation reduces the dose delivered by incident ions. The other mechanism by which dose can be reduced is ionization energy loss, which can lead to some particles stopping in the shielding. This is the conventional notion of shielding, but it is not applicable to human spaceflight since the particles in the GCR tend to be too energetic to be stopped in the relatively thin shielding that is possible within payload mass constraints. Our group has measured a large number of fragmentation cross sections, intended to be used as input to, or for validation of, NASA's radiation transport models. A database containing over 200 charge-changing cross sections and over 2000 fragment production cross sections has been compiled. In this report, we examine in detail the contrast between fragment measurements at large acceptance and small acceptance. We use output from the PHITS Monte Carlo code to test our assumptions using as an example 40Ar data (and simulated data) at a beam energy of 650 MeV/nucleon. We also present preliminary analysis in which isotopic resolution was attained for beryllium fragments produced by beams of 10B and 11B. Future work on the experimental data set will focus on extracting and interpreting production cross sections for light fragments.

  4. Parental Factors in Children’s Active Transport to School

    PubMed Central

    Henne, Heather M.; Tandon, Pooja S.; Frank, Larry D.; Saelens, Brian E.

    2014-01-01

    Objective Identify non-distance factors related to children’s active transport (AT) to school, including parental, home, and environment characteristics. Understanding the factors related to children’s AT to school, beyond distance to school, could inform interventions to increase AT and children’s overall physical activity. Study Design Participants were in the Neighborhood Impact on Kids Study, a longitudinal, observational cohort study of children aged 6 - 11 and their parents in King County, WA and San Diego County, CA between 2007-2009. Parents reported frequency and mode of child transport to school, perceived neighborhood, home and family environments, parental travel behaviors, and sociodemographics. Methods Children living less than a 20 minute walk to school were in this analysis. Children classified as active transporters (walked/bicycled to or from school at least once per week) were compared with those not using AT as often. Results Children using AT were older and had parents who reported themselves using active transport. Having a family rule that restricts the child to stay within sight of the parent or home and more parent working hours was related to lower odds of a child using AT. Conclusions Children’s AT to school is associated with parental AT to work and other locations. Interventions should be considered that enable whole family AT, ameliorate safety concerns and decrease the need for parental supervision, such as walking school buses. PMID:24999161

  5. A Fuzzy Modeling Approach to Road Transport with Application to a Case of Spent Nuclear Fuel Transport

    SciTech Connect

    Marseguerra, Marzio; Zio, Enrico; Bianchi, Mauro

    2004-06-15

    In this paper, we propose a general fuzzy inference approach to building a model of hazardous road transport that relates given traffic, weather, and vehicle-speed conditions to the accident rate. The development of the model is discussed in detail, and its validation is provided with reference to literature data regarding the transport of spent nuclear fuel to its final confinement repository.

  6. Solar modulation and nuclear fragmentation effects in galactic cosmic ray transport through shielding

    NASA Technical Reports Server (NTRS)

    Townsend, L. W.; Cucinotta, C. F.; Wilson, J. W.; Shinn, J. L.; Badhwar, G.

    1994-01-01

    Crews of manned interplanetary missions may accumulate significant radiation exposures from the Galactic Cosmic Ray (GCR) environment in space. Estimates of how these dose levels are affected by the assumed temporal and spatial variations in the composition of the GCR environment, and by the effects of the spacecraft and body self-shielding on the transported fields are presented. In this work, the physical processes through which shielding alters the transported radiation fields are described. We then present estimates of the effects on model calculations of (1) nuclear fragmentation model uncertainties, (2) solar modulation, (3) variations between solar cycles, and (4) proposed changes to the quality factors which relate dose equivalent to absorbed dose.

  7. 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. PMID:26427884

  8. Site Specific Analyses of a Spent Nuclear Fuel Transportation Accident

    SciTech Connect

    Biwer, B. M.; Chen, S. Y.

    2003-02-24

    The number of spent nuclear fuel (SNF) shipments is expected to increase significantly during the time period that the United States' inventory of SNF is sent to a final disposal site. Prior work estimated that the highest accident risks of a SNF shipping campaign to the proposed geologic repository at Yucca Mountain were in the corridor states, such as Illinois. The largest potential human health impacts would be expected to occur in areas with high population densities such as urban settings. Thus, our current study examined the human health impacts from the most plausible severe SNF transportation accidents in the Chicago metropolitan area. The RISKIND 2.0 program was used to model site-specific data for an area where the largest impacts might occur. The results have shown that the radiological human health consequences of a severe SNF rail transportation accident on average might be similar to one year of exposure to natural background radiation for those persons living a nd working in the most affected areas downwind of the actual accident location. For maximally exposed individuals, an exposure similar to about two years of exposure to natural background radiation was estimated. In addition to the accident probabilities being very low (approximately 1 chance in 10,000 or less during the entire shipping campaign), the actual human health impacts are expected to be lower if any of the accidents considered did occur, because the results are dependent on the specific location and weather conditions, such as wind speed and direction, that were selected to maximize the results. Also, comparison of the results of longer duration accident scenarios against U.S. Environmental Protection Agency guidelines was made to demonstrate the usefulness of this site-specific analysis for emergency planning purposes.

  9. 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

  10. Nuclear reaction effects in use of newly recommended quality factor

    NASA Technical Reports Server (NTRS)

    Shinn, Judy L.; Wilson, John W.

    1991-01-01

    The biological risk for energetic ion exposure cannot be reliably estimated exclusive of the target nuclear reaction products produced within the local tissue. A theoretical basis is derived for evaluating target fragment contributions that are evaluated for the newly proposed quality factor.

  11. 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.

  12. 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

  13. 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.

  14. Monocarboxylate Transporter-1 Is Required for Cell Death in Mouse Chondrocytic ATDC5 Cells Exposed to Interleukin-1β via Late Phase Activation of Nuclear Factor κB and Expression of Phagocyte-type NADPH Oxidase*

    PubMed Central

    Yoshimura, Kentaro; Miyamoto, Yoichi; Yasuhara, Rika; Maruyama, Toshifumi; Akiyama, Tomohito; Yamada, Atsushi; Takami, Masamichi; Suzawa, Tetsuo; Tsunawaki, Shoko; Tachikawa, Tetsuhiko; Baba, Kazuyoshi; Kamijo, Ryutaro

    2011-01-01

    Interleukin-1β (IL-1β) induces cell death in chondrocytes in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner. In this study, increased production of lactate was observed in IL-1β-treated mouse chondrocytic ATDC5 cells prior to the onset of their death. IL-1β-induced cell death in ATDC5 cells was suppressed by introducing an siRNA for monocarboxylate transporter-1 (MCT-1), a lactate transporter distributed in plasma and mitochondrial inner membranes. Mct-1 knockdown also prevented IL-1β-induced expression of phagocyte-type NADPH oxidase (NOX-2), an enzyme specialized for production of ROS, whereas it did not have an effect on inducible NO synthase. Suppression of IL-1β-induced cell death by Nox-2 siRNA indicated that NOX-2 is involved in cell death. Phosphorylation and degradation of inhibitor of κBα (IκBα) from 5 to 20 min after the addition of IL-1β was not affected by Mct-1 siRNA. In addition, IκBα was slightly decreased after 12 h of incubation with IL-1β, and the decrease was prominent after 36 h, whereas activation of p65/RelA was observed from 12 to 48 h after exposure to IL-1β. These changes were not seen in Mct-1-silenced cells. Forced expression of IκBα super repressor as well as treatment with the IκB kinase inhibitor BAY 11-7082 suppressed NOX-2 expression. Furthermore, Mct-1 siRNA lowered the level of ROS generated after 15-h exposure to IL-1β, whereas a ROS scavenger, N-acetylcysteine, suppressed both late phase degradation of IκBα and Nox-2 expression. These results suggest that MCT-1 contributes to NOX-2 expression via late phase activation of NF-κB in a ROS-dependent manner in ATDC5 cells exposed to IL-1β. PMID:21372137

  15. Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-1beta via late phase activation of nuclear factor kappaB and expression of phagocyte-type NADPH oxidase.

    PubMed

    Yoshimura, Kentaro; Miyamoto, Yoichi; Yasuhara, Rika; Maruyama, Toshifumi; Akiyama, Tomohito; Yamada, Atsushi; Takami, Masamichi; Suzawa, Tetsuo; Tsunawaki, Shoko; Tachikawa, Tetsuhiko; Baba, Kazuyoshi; Kamijo, Ryutaro

    2011-04-29

    Interleukin-1β (IL-1β) induces cell death in chondrocytes in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner. In this study, increased production of lactate was observed in IL-1β-treated mouse chondrocytic ATDC5 cells prior to the onset of their death. IL-1β-induced cell death in ATDC5 cells was suppressed by introducing an siRNA for monocarboxylate transporter-1 (MCT-1), a lactate transporter distributed in plasma and mitochondrial inner membranes. Mct-1 knockdown also prevented IL-1β-induced expression of phagocyte-type NADPH oxidase (NOX-2), an enzyme specialized for production of ROS, whereas it did not have an effect on inducible NO synthase. Suppression of IL-1β-induced cell death by Nox-2 siRNA indicated that NOX-2 is involved in cell death. Phosphorylation and degradation of inhibitor of κBα (IκBα) from 5 to 20 min after the addition of IL-1β was not affected by Mct-1 siRNA. In addition, IκBα was slightly decreased after 12 h of incubation with IL-1β, and the decrease was prominent after 36 h, whereas activation of p65/RelA was observed from 12 to 48 h after exposure to IL-1β. These changes were not seen in Mct-1-silenced cells. Forced expression of IκBα super repressor as well as treatment with the IκB kinase inhibitor BAY 11-7082 suppressed NOX-2 expression. Furthermore, Mct-1 siRNA lowered the level of ROS generated after 15-h exposure to IL-1β, whereas a ROS scavenger, N-acetylcysteine, suppressed both late phase degradation of IκBα and Nox-2 expression. These results suggest that MCT-1 contributes to NOX-2 expression via late phase activation of NF-κB in a ROS-dependent manner in ATDC5 cells exposed to IL-1β. PMID:21372137

  16. Comprehensive transportation risk assessment system based on unit-consequence factors

    SciTech Connect

    Biwer, B.M.; Monette, F.A.; LePoire, D.J.; Chen, S.Y.

    1994-02-01

    The U.S. Department of Energy (DOE) Environmental Restoration and Waste Management Programmatic Environmental Impact Statement requires a comprehensive transportation risk analysis of radioactive waste shipments for large shipping campaigns. Thousands of unique shipments involving truck and rail transport must be analyzed; a comprehensive risk analysis is impossible with currently available methods. Argonne National Laboratory developed a modular transportation model that can handle the demands imposed by such an analysis. The modular design of the model facilitates the simple addition/updating of transportation routes and waste inventories, as required, and reduces the overhead associated with file maintenance and quality assurance. The model incorporates unit-consequences factors generated with the RADTRAN 4 transportation risk analysis code that are combined with an easy-to-use, menu-driven interface on IBM-compatible computers running under DOS. User selection of multiple origin/destination site pairs for the shipment of multiple radioactive waste inventories is permitted from pop-up lists. Over 800 predefined routes are available among more than 30 DOE sites and waste inventories that include high-level waste, spent nuclear fuel, transuranic waste, low-level waste, low-level mixed waste, and greater-than-Class C waste.

  17. cAMP Response Element-binding Protein (CREB) and Nuclear Factor κB Mediate the Tamoxifen-induced Up-regulation of Glutamate Transporter 1 (GLT-1) in Rat Astrocytes*

    PubMed Central

    Karki, Pratap; Webb, Anton; Smith, Keisha; Lee, Kyuwon; Son, Deok-Soo; Aschner, Michael; Lee, Eunsook

    2013-01-01

    Tamoxifen (TX), a selective estrogen receptor modulator, exerts antagonistic effects on breast tissue and is used to treat breast cancer. Recent evidence also suggests that it may act as an agonist in brain tissue. We reported previously that TX enhanced the expression and function of glutamate transporter 1 (GLT-1) in rat astrocytes, an effect that was mediated by TGF-α. To gain further insight into the mechanisms that mediate TX-induced up-regulation of GLT-1 (EAAT2 in humans), we investigated its effect on GLT-1 at the transcriptional level. TX phosphorylated the cAMP response element-binding protein (CREB) and recruited CREB to the GLT-1 promoter consensus site. The effect of TX on astrocytic GLT-1 was attenuated by the inhibition of PKA, the upstream activator of the CREB pathway. In addition, the effect of TX on GLT-1 promoter activity was abolished by the inhibition of the NF-κB pathway. Furthermore, TX recruited the NF-κB subunits p65 and p50 to the NF-κB binding domain of the GLT-1 promoter. Mutation of NF-κB (triple, −583/-282/-251) or CRE (-308) sites on the GLT-1 promoter led to significant repression of the promoter activity, but neither mutant completely abolished the TX-induced GLT-1 promoter activity. Mutation of both the NF-κB (-583/-282/-251) and CRE (-308) sites led to a complete abrogation of the effect of TX on GLT-1 promoter activity. Taken together, our findings establish that TX regulates GLT-1 via the CREB and NF-κB pathways. PMID:23955341

  18. Additional thyroid dose factor from transportation sources in Russia after the Chernobyl disaster.

    PubMed Central

    Parshkov, E M; Chebotareva, I V; Sokolov, V A; Dallas, C E

    1997-01-01

    Beginning approximately 4 years after the Chernobyl nuclear accident a steady increase in the incidence of thyroid cancer was observed in children and adolescents of the Bryansk Oblast, which received the highest level of radionuclide contaminants in Russia. We examined the spatial relationship between the residence location of patients with identified thyroid cancer (0-18 years old at the time of the accident) and a number of geographic parameters to better account for the etiology of thyroid cancer spatial distribution. Geographic parameters analyzed included spatial distribution of 137Cs and 131I in soil, population demographics, measurements and reconstructions. of absorbed thyroid 131I doses in the population, and maps of major transportation arteries. An interesting finding is the lack of a consistent correlation between the spatial distribution of radionuclides in the soil and thyroid cancer incidence. Instead, most of the thyroid cancer cases were diagnosed in settlements situated on major railways and roads. Correlating population with thyroid cancer cases and transportation arteries reveals a much higher cancer rate on or near major roads and railways than at a distance from them, again independent of radionuclide soil concentration. There are other important factors, of course, that must be considered in future evaluations of this phenomenon. These include the influence of iodine endemic zones, genetic predisposition to thyroid cancer, and duration of residence time in contaminated areas. The feasibility of radionuclide transport on railways and roads is discussed, together with the vectors for transfer of the contaminants to the human population. Developing a model to reconstruct the radiation dose to the thyroid over time in this geographic region is proposed in light of the impact of transportation arteries. Specific studies are outlined to provide the data necessary to develop this model as well as to better characterize the feasibility and

  19. STE6, the yeast a-factor transporter.

    PubMed

    Michaelis, S

    1993-02-01

    In eukaryotic cells, most extracellular proteins exit the cell via the classical secretory pathway (ER-->Golgi-->secretory vesicles). A notable exception to this pattern is the Saccharomyces cerevisiae mating pheromone alpha-factor, an isoprenylated, methylated, oligopeptide signaling molecule which uses a distinctly non-classical mechanism for secretion. Export of alpha-factor from the yeast cell is mediated by STE6, a member of the ABC protein superfamily. STE6 is one of the few eukaryotic ABC proteins for which a true physiological substrate is known. The ability to carry out molecular manipulations with ease in yeast, together with the possibility of probing substrate-transporter interactions via genetic analysis, affords an excellent opportunity to rigorously dissect the workings of this ABC family member. PMID:8095825

  20. 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.

  1. 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.

  2. 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

  3. Nuclear factor-E2-related factor 2 is a major determinant of bile acid homeostasis in the liver and intestine

    PubMed Central

    Weerachayaphorn, Jittima; Mennone, Albert; Soroka, Carol J.; Harry, Kathy; Hagey, Lee R.; Kensler, Thomas W.

    2012-01-01

    The transcription factor nuclear factor-E2-related factor 2 (Nrf2) is a key regulator for induction of hepatic detoxification and antioxidant mechanisms, as well as for certain hepatobiliary transporters. To examine the role of Nrf2 in bile acid homeostasis and cholestasis, we assessed the determinants of bile secretion and bile acid synthesis and transport before and after bile duct ligation (BDL) in Nrf2−/− mice. Our findings indicate reduced rates of biliary bile acid and GSH excretion, higher levels of intrahepatic bile acids, and decreased expression of regulators of bile acid synthesis, Cyp7a1 and Cyp8b1, in Nrf2−/− compared with wild-type control mice. The mRNA expression of the bile acid transporters bile salt export pump (Bsep) and organic solute transporter (Ostα) were increased in the face of impaired expression of the multidrug resistance-associated proteins Mrp3 and Mrp4. Deletion of Nrf2 also decreased ileal apical sodium-dependent bile acid transporter (Asbt) expression, leading to reduced bile acid reabsorption and increased loss of bile acid in feces. Finally, when cholestasis is induced by BDL, liver injury was not different from that in wild-type BDL mice. These Nrf2−/− mice also had increased pregnane X receptor (Pxr) and Cyp3a11 mRNA expression in association with enhanced hepatic bile acid hydroxylation. In conclusion, this study finds that Nrf2 plays a major role in the regulation of bile acid homeostasis in the liver and intestine. Deletion of Nrf2 results in a cholestatic phenotype but does not augment liver injury following BDL. PMID:22345550

  4. 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.

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

    PubMed

    Wang, Lei; Ma, Hao; Fu, Liyuan; Yao, Jianbo

    2014-12-01

    Nuclear proteins are required for the initiation of transcription in early embryos before embryonic genome activation. The regulated transport of nuclear proteins is mediated by factors known as importins (karyopherins). Kpna7, a newly discovered member of the importin α family, is critical for early development in mammals. In this study, we characterize rainbow trout Kpna7. The cDNA for rainbow trout Kpna7 encodes a 519 amino acid protein that contains a conserved importin β binding (IBB) domain and seven armadillo/beta-catenin-like repeat (ARM) motifs. Reverse-transcriptase PCR and Western blot analyses revealed that Kpna7 is specifically expressed in eggs/ovary. Real-time PCR analysis demonstrated that expression of Kpna7 mRNA is high in unfertilized eggs, gradually decreases in early-stage embryos until 3 days post-fertilization, and declines sharply thereafter, reaching a level that is barely detectable in 4-day-old embryos. Using a yeast two-hybrid screening system, we identified two Kpna7-interacting proteins from a rainbow trout egg cDNA library: Stl3 (rhamnose-binding lectin 3) and an uncharacterized protein. Both genes appear to be expressed specifically in eggs/testis. Co-immunoprecipitation assays confirmed the interaction between Kpna7 and Stl3, and co-transfection experiments using EGFP-tagged Stl3 showed that Kpna7 facilitates the nuclear transport of Stl3 through an interaction with the predicted nuclear-localization signal cluster at the carboxy-terminus of Stl3. Our data suggest that Kpna7 may function in early embryonic development as a unique nuclear transporter for egg-specific proteins. PMID:25511304

  6. Nuclear modification factor in an anisotropic quark-gluon plasma

    NASA Astrophysics Data System (ADS)

    Mandal, Mahatsab; Bhattacharya, Lusaka; Roy, Pradip

    2011-10-01

    We calculate the nuclear modification factor (RAA) of light hadrons by taking into account the initial state momentum anisotropy of the quark-gluon plasma (QGP) expected to be formed in relativistic heavy ion collisions. Such an anisotropy can result from the initial rapid longitudinal expansion of the matter. A phenomenological model for the space-time evolution of the anisotropic QGP is used to obtain the time dependence of the anisotropy parameter ξ and the hard momentum scale, phard. The result is then compared with the PHENIX experimental data to constrain the isotropization time scale, τiso for fixed initial conditions (FIC). It is shown that the extracted value of τiso lies in the range 0.5⩽τiso⩽1.5. However, using a fixed final multiplicity (FFM) condition does not lead to any firm conclusion about the extraction of the isotropization time. The present calculation is also extended to contrast with the recent measurement of nuclear modification factor by the ALICE collaboration at s=2.76 TeV. It is argued that in the present approach, the extraction of τiso at this energy is uncertain and, therefore, refinement of the model is necessary. The sensitivity of the results on the initial conditions has been discussed. We also present the nuclear modification factor at Large Hadron Collider (LHC) energies with s=5.5 TeV.

  7. Nuclear actions of insulin-like growth factor binding protein-3.

    PubMed

    Baxter, Robert C

    2015-09-10

    In addition to its actions outside the cell, cellular uptake and nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) has been recognized for almost two decades, but knowledge of its nuclear actions has been slow to emerge. IGFBP-3 has a functional nuclear localization signal and interacts with the nuclear transport protein importin-β. Within the nucleus IGFBP-3 appears to have a role in transcriptional regulation. It can bind to the nuclear receptor, retinoid X receptor-α and several of its dimerization partners, including retinoic acid receptor, vitamin D receptor (VDR), and peroxisome proliferator-activated receptor-γ (PPARγ). These interactions modulate the functions of these receptors, for example inhibiting VDR-dependent transcription in osteoblasts and PPARγ-dependent transcription in adipocytes. Nuclear IGFBP-3 can be detected by immunohistochemistry in cancer and other tissues, and its presence in the nucleus has been shown in many cell culture studies to be necessary for its pro-apoptotic effect, which may also involve interaction with the nuclear receptor Nur77, and export from the nucleus. IGFBP-3 is p53-inducible and in response to DNA damage, forms a complex with the epidermal growth factor receptor (EGFR), translocating to the nucleus to interact with DNA-dependent protein kinase. Inhibition of EGFR kinase activity or downregulation of IGFBP-3 can inhibit DNA double strand-break repair by nonhomologous end joining. IGFBP-3 thus has the ability to influence many cell functions through its interactions with intranuclear pathways, but the importance of these interactions in vivo, and their potential to be targeted for therapeutic benefit, require further investigation. PMID:26074086

  8. 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

  9. 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.

  10. BGLF4 Kinase Modulates the Structure and Transport Preference of the Nuclear Pore Complex To Facilitate Nuclear Import of Epstein-Barr Virus Lytic Proteins

    PubMed Central

    Chang, Chou-Wei; Lee, Chung-Pei; Su, Mei-Tzu; Tsai, Ching-Hwa

    2014-01-01

    ABSTRACT BGLF4 kinase, the only Ser/Thr protein kinase encoded by the Epstein-Barr virus (EBV) genome, phosphorylates multiple viral and cellular substrates to optimize the cellular environment for viral DNA replication and the nuclear egress of nucleocapsids. Previously, we found that nuclear targeting of BGLF4 is through direct interaction with the FG repeat-containing nucleoporins (FG-Nups) Nup62 and Nup153 independently of cytosolic transport factors. Here, we investigated the regulatory effects of BGLF4 on the structure and biological functions of the nuclear pore complex (NPC). In EBV-positive NA cells, the distribution of FG-Nups was modified during EBV reactivation. In transfected cells, BGLF4 changed the staining pattern of Nup62 and Nup153 in a kinase activity-dependent manner. Detection with anti-phospho-Ser/Thr-Pro MPM-2 antibody demonstrated that BGLF4 induced the phosphorylation of Nup62 and Nup153. The nuclear targeting of importin β was attenuated in the presence of BGLF4, leading to inhibition of canonical nuclear localization signal (NLS)-mediated nuclear import. An in vitro nuclear import assay revealed that BGLF4 induced the nuclear import of larger molecules. Notably, we found that BGLF4 promoted the nuclear import of several non-NLS-containing EBV proteins, including the viral DNA-replicating enzymes BSLF1, BBLF2/3, and BBLF4 and the major capsid protein (VCA), in cotransfected cells. The data presented here suggest that BGLF4 interferes with the normal functions of Nup62 and Nup153 and preferentially helps the nuclear import of viral proteins for viral DNA replication and assembly. In addition, the nuclear import-promoting activity was found in cells expressing the BGLF4 homologs of another two gammaherpesviruses but not those from alpha- and betaherpesviruses. IMPORTANCE During lytic replication, many EBV genome-encoded proteins need to be transported into the nucleus, not only for viral DNA replication but also for the assembly of

  11. 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 REGULATORY AUTHORITY IN AGREEMENT STATES AND IN OFFSHORE WATERS UNDER SECTION 274 Reciprocity §...

  12. 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 REGULATORY AUTHORITY IN AGREEMENT STATES AND IN OFFSHORE WATERS UNDER SECTION 274 Reciprocity §...

  13. 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 REGULATORY AUTHORITY IN AGREEMENT STATES AND IN OFFSHORE WATERS UNDER SECTION 274 Reciprocity §...

  14. 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).

  15. 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

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Blue Ribbon Commission on America's Nuclear Future, Transportation and Storage Subcommittee AGENCY: Office of... subcommittee of the Blue Ribbon Commission on America's Nuclear Future (the Commission). The establishment...

  16. 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

  17. 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

  18. 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.

  19. The Effects of Geographic and Management Factors on the Cost of Pupil Transportation.

    ERIC Educational Resources Information Center

    Alspaugh, John W.

    1996-01-01

    Examines the relationship between school districts' geography and management strategies and their collective influence on student transportation cost, using 1990-91 data from 533 Missouri school districts. Management factors influence transportation costs more than geography does. When both factors are considered, contracted transportation is more…

  20. 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

  1. 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

  2. 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

  3. 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

  4. Proaggregant nuclear factor(s) trigger rapid formation of α-synuclein aggregates in apoptotic neurons.

    PubMed

    Jiang, Peizhou; Gan, Ming; Yen, Shu-Hui; Moussaud, Simon; McLean, Pamela J; Dickson, Dennis W

    2016-07-01

    Cell-to-cell transmission of α-synuclein (αS) aggregates has been proposed to be responsible for progressive αS pathology in Parkinson disease (PD) and related disorders, including dementia with Lewy bodies. In support of this concept, a growing body of in vitro and in vivo experimental evidence shows that exogenously introduced αS aggregates can spread into surrounding cells and trigger PD-like pathology. It remains to be determined what factor(s) lead to initiation of αS aggregation that is capable of seeding subsequent propagation. In this study we demonstrate that filamentous αS aggregates form in neurons in response to apoptosis induced by staurosporine or other toxins-6-hydroxy-dopamine and 1-methyl-4-phenylpyridinium (MPP+). Interaction between αS and proaggregant nuclear factor(s) is associated with disruption of nuclear envelope integrity. Knocking down a key nuclear envelop constituent protein, lamin B1, enhances αS aggregation. Moreover, in vitro and in vivo experimental models demonstrate that aggregates released upon cell breakdown can be taken up by surrounding cells. Accordingly, we suggest that at least some αS aggregation might be related to neuronal apoptosis or loss of nuclear membrane integrity, exposing cytosolic α-synuclein to proaggregant nuclear factors. These findings provide new clues to the pathogenesis of PD and related disorders that can lead to novel treatments of these disorders. Specifically, finding ways to limit the effects of apoptosis on αS aggregation, deposition, local uptake and subsequent propagation might significantly impact progression of disease. PMID:26839082

  5. 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.

  6. Measurements of ϒ Production and Nuclear Modification Factor at STAR

    NASA Astrophysics Data System (ADS)

    Kesich, Anthony

    2013-08-01

    Thermal suppression of quarkonium production in heavy-ion collisions, due to Debye screening of the quark-antiquark potential, has been proposed as a clear signature of Quark-Gluon Plasma (QGP) formation. At RHIC energies, the ϒ meson is a clean probe of the early system due to negligible levels of enhancement from bbbar recombination and non-thermal suppression from co-mover absorption. We report on our measurement of the ϒ →e+e- cross section in Au+Au collisions at √{sNN} = 200 GeV. We compute the Nuclear Modification Factor by comparing these results to new p+p measurements from 2009 (21pb-1 in 2009 compared to 7.9pb-1 in 2006). In order to have a complete assessment of both hot and cold nuclear matter effects on Upsilon production we also report on results from d+Au collisions.

  7. Human Factors Engineering Review Model for advanced nuclear power reactors

    SciTech Connect

    O'Hara, J.; Higgins, J. ); Goodman, C.; Galletti, G.: Eckenrode, R. )

    1993-01-01

    One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model's rationale, scope, objectives, development, general characteristics. and application.

  8. Human Factors Engineering Review Model for advanced nuclear power reactors

    SciTech Connect

    O`Hara, J.; Higgins, J.; Goodman, C.; Galletti, G.: Eckenrode, R.

    1993-05-01

    One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model`s rationale, scope, objectives, development, general characteristics. and application.

  9. 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

  10. 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

  11. Energy- and temperature-dependent transport of integral proteins to the inner nuclear membrane via the nuclear pore

    PubMed Central

    Ohba, Tomoyuki; Schirmer, Eric C.; Nishimoto, Takeharu; Gerace, Larry

    2004-01-01

    Resident integral proteins of the inner nuclear membrane (INM) are synthesized as membrane-integrated proteins on the peripheral endoplasmic reticulum (ER) and are transported to the INM throughout interphase using an unknown trafficking mechanism. To study this transport, we developed a live cell assay that measures the movement of transmembrane reporters from the ER to the INM by rapamycin-mediated trapping at the nuclear lamina. Reporter constructs with small (<30 kD) cytosolic and lumenal domains rapidly accumulated at the INM. However, increasing the size of either domain by 47 kD strongly inhibited movement. Reduced temperature and ATP depletion also inhibited movement, which is characteristic of membrane fusion mechanisms, but pharmacological inhibition of vesicular trafficking had no effect. Because reporter accumulation at the INM was inhibited by antibodies to the nuclear pore membrane protein gp210, our results support a model wherein transport of integral proteins to the INM involves lateral diffusion in the lipid bilayer around the nuclear pore membrane, coupled with active restructuring of the nuclear pore complex. PMID:15611332

  12. Excited nuclear matter at Fermi energies: From transport properties to the equation of state

    NASA Astrophysics Data System (ADS)

    Lopez, O.; Durand, D.; Lehaut, G.

    2016-05-01

    Properties of excited nuclear matter are one of the main subject of investigation in Nuclear Physics. Indeed, the response of nuclear matter under extreme conditions encountered in heavy-ion induced reactions (large compression, thermal and collective excitations, isopin diffusion) around the Fermi energy is strongly needed when studying the nuclear equation of state and the underlying in-medium properties concerning the nuclear interaction. In this contribution, we will present some experimental results concerning the transport properties of nuclear matter, focusing specifically on the determination of in-medium quantities such as mean free pathes and nucleon-nucleon cross sections around the Fermi energy. We will see that, in this specific energy range, energy and isospin dissipations exhibit very peculiar features, such as the crossover between 1-body to 2-body dissipation regimes corresponding to the transition between the nuclear response from Mean-Field to the nucleonic response through the appearance of nucleon-nucleon collisions.

  13. Nuclear Control of Respiratory Chain Expression by Nuclear Respiratory Factors and PGC-1-Related Coactivator

    PubMed Central

    Scarpulla, Richard C.

    2010-01-01

    Expression of the respiratory apparatus depends on both nuclear and mitochondrial genes. Although these genes are sequestered in distinct cellular organelles, their transcription relies on nucleus-encoded factors. Certain of these factors are directed to the mitochondria, where they sponsor the bi-directional transcription of mitochondrial DNA. Others act on nuclear genes that encode the majority of the respiratory subunits and many other gene products required for the assembly and function of the respiratory chain. The nuclear respiratory factors, NRF-1 and NRF-2, contribute to the expression of respiratory subunits and mitochondrial transcription factors and thus have been implicated in nucleo-mitochondrial interactions. In addition, coactivators of the PGC-1 family serve as mediators between the environment and the transcriptional machinery governing mitochondrial biogenesis. One family member, peroxisome proliferator-activated receptor γ coactivator PGC-1-related coactivator (PRC), is an immediate early gene product that is rapidly induced by mitogenic signals in the absence of de novo protein synthesis. Like other PGC-1 family members, PRC binds NRF-1 and activates NRF-1 target genes. In addition, PRC complexes with NRF-2 and HCF-1 (host cell factor-1) in the activation of NRF-2-dependent promoters. HCF-1 functions in cell-cycle progression and has been identified as an NRF-2 coactivator. The association of these factors with PRC is suggestive of a role for the complex in cell growth. Finally, shRNA-mediated knock down of PRC expression results in a complex phenotype that includes the inhibition of respiratory growth on galactose and the loss of respiratory complexes. Thus, PRC may help integrate the expression of the respiratory apparatus with the cell proliferative program. PMID:19076454

  14. Risk factors, endothelial cell turnover and lipid transport in atherogenesis.

    PubMed

    Lin, S J

    1996-11-01

    Cardiovascular diseases remain to be the 4th rank of top ten causes of mortality in Taiwan in recent years. Atherosclerosis and coronary artery disease, which often culminating in the occurrence of myocardial infarction and congestive heart failure, are responsible for the majority of these death. One of the prominent features of atherosclerotic lesion is local accumulation of lipids, mainly in the forms of cholesteryl ester and free cholesterol, either within cells or extracellularly in matrix. Repeated endothelial injury and enhanced lipid infiltration are critical events in the development of atherosclerosis. Plasma lipoproteins may enter the arterial wall through endothelium, either transcellularly via vesicular transport or paracellularly via intercellular junction. Our previous studies have demonstrated that most of the arterial endothelial cells in mitosis are associated with the leakage of fluorescently labeled albumin and low density lipoproteins. Subsequently, such transendothelial leakage of macromolecules is also shown to be associated with endothelial cell death as assessed by immunocytochemical staining for IgG. These findings suggested that transiently leaky junctions occurring during endothelial cell turnover may provide potentially important pathways for increasing transport or leakage of macromolecules, including atherogenic LDL, across the vascular endothelium. Electron microscopic study using horseradish peroxidase as a tracer revealed markedly widening of intercellular junctions around endothelial cells in mitosis providing direct evidence in support of "cell turnover-leaky junction" theory for the localization of atherogenesis. Hypertension, smoking, diabetes, and hyperlipidemia are well-known major risk factors for atherosclerosis and coronary heart disease. In a series of investigations, we examined the hypothesis that hypertension smoking, diabetes, and hyperlipidemia increase the arterial endothelial cell turnover and hence

  15. 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

  16. 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.

  17. 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.

  18. Nucleolin regulates phosphorylation and nuclear export of fibroblast growth factor 1 (FGF1).

    PubMed

    Sletten, Torunn; Kostas, Michal; Bober, Joanna; Sorensen, Vigdis; Yadollahi, Mandana; Olsnes, Sjur; Tomala, Justyna; Otlewski, Jacek; Zakrzewska, Malgorzata; Wiedlocha, Antoni

    2014-01-01

    Extracellular fibroblast growth factor 1 (FGF1) acts through cell surface tyrosine kinase receptors, but FGF1 can also act directly in the cell nucleus, as a result of nuclear import of endogenously produced, non-secreted FGF1 or by transport of extracellular FGF1 via endosomes and cytosol into the nucleus. In the nucleus, FGF1 can be phosphorylated by protein kinase C δ (PKCδ), and this event induces nuclear export of FGF1. To identify intracellular targets of FGF1 we performed affinity pull-down assays and identified nucleolin, a nuclear multifunctional protein, as an interaction partner of FGF1. We confirmed a direct nucleolin-FGF1 interaction by surface plasmon resonance and identified residues of FGF1 involved in the binding to be located within the heparin binding site. To assess the biological role of the nucleolin-FGF1 interaction, we studied the intracellular trafficking of FGF1. In nucleolin depleted cells, exogenous FGF1 was endocytosed and translocated to the cytosol and nucleus, but FGF1 was not phosphorylated by PKCδ or exported from the nucleus. Using FGF1 mutants with reduced binding to nucleolin and a FGF1-phosphomimetic mutant, we showed that the nucleolin-FGF1 interaction is critical for the intranuclear phosphorylation of FGF1 by PKCδ and thereby the regulation of nuclear export of FGF1. PMID:24595027

  19. Multiple Nuclear Localization Signals Mediate Nuclear Localization of the GATA Transcription Factor AreA

    PubMed Central

    Hunter, Cameron C.; Siebert, Kendra S.; Downes, Damien J.; Wong, Koon Ho; Kreutzberger, Sara D.; Fraser, James A.; Clarke, David F.; Hynes, Michael J.; Davis, Meryl A.

    2014-01-01

    The Aspergillus nidulans GATA transcription factor AreA activates transcription of nitrogen metabolic genes in response to nitrogen limitation and is known to accumulate in the nucleus during nitrogen starvation. Sequence analysis of AreA revealed multiple nuclear localization signals (NLSs), five putative classical NLSs conserved in fungal AreA orthologs but not in the Saccharomyces cerevisiae functional orthologs Gln3p and Gat1p, and one putative noncanonical RRX33RXR bipartite NLS within the DNA-binding domain. In order to identify the functional NLSs in AreA, we constructed areA mutants with mutations in individual putative NLSs or combinations of putative NLSs and strains expressing green fluorescent protein (GFP)-AreA NLS fusion genes. Deletion of all five classical NLSs individually or collectively did not affect utilization of nitrogen sources or AreA-dependent gene expression and did not prevent AreA nuclear localization. Mutation of the bipartite NLS conferred the inability to utilize alternative nitrogen sources and abolished AreA-dependent gene expression likely due to effects on DNA binding but did not prevent AreA nuclear localization. Mutation of all six NLSs simultaneously prevented AreA nuclear accumulation. The bipartite NLS alone strongly directed GFP to the nucleus, whereas the classical NLSs collaborated to direct GFP to the nucleus. Therefore, AreA contains multiple conserved NLSs, which show redundancy and together function to mediate nuclear import. The noncanonical bipartite NLS is conserved in GATA factors from Aspergillus, yeast, and mammals, indicating an ancient origin. PMID:24562911

  20. 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. PMID:23649804

  1. 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

  2. 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

  3. 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. PMID:25299942

  4. Electronic correlation and transport properties of nuclear fuel materials

    SciTech Connect

    Yin Quan; Kutepov, Andrey; Haule, Kristjan; Kotliar, Gabriel; Savrasov, Sergey Y.; Pickett, Warren E.

    2011-11-15

    The electronic structures and transport properties of a series of actinide monocarbides, mononitrides, and dioxides are studied systematically using a combination of density-functional theory and dynamical mean-field theory. The studied materials present different electronic correlation strength and degree of localization of 5f electrons, where a metal-insulator boundary naturally lies within. In the spectral function of Mott-insulating uranium oxide, a resonance peak is observed in both theory and experiment and may be understood as a generalized Zhang-Rice state. We also investigate the interplay between electron-electron and electron-phonon interactions, both of which are responsible for the transport in the metallic compounds. Our findings allow us to gain insight in the roles played by different scattering mechanisms, and suggest how to improve their thermal conductivities.

  5. Electronic correlation and transport properties of nuclear fuel materials

    NASA Astrophysics Data System (ADS)

    Yin, Quan; Kutepov, Andrey; Haule, Kristjan; Kotliar, Gabriel; Savrasov, Sergey Y.; Pickett, Warren E.

    2011-11-01

    The electronic structures and transport properties of a series of actinide monocarbides, mononitrides, and dioxides are studied systematically using a combination of density-functional theory and dynamical mean-field theory. The studied materials present different electronic correlation strength and degree of localization of 5f electrons, where a metal-insulator boundary naturally lies within. In the spectral function of Mott-insulating uranium oxide, a resonance peak is observed in both theory and experiment and may be understood as a generalized Zhang-Rice state. We also investigate the interplay between electron-electron and electron-phonon interactions, both of which are responsible for the transport in the metallic compounds. Our findings allow us to gain insight in the roles played by different scattering mechanisms, and suggest how to improve their thermal conductivities.

  6. 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.

  7. Snail nuclear transport: the gateways regulating epithelial-to-mesenchymal transition?

    PubMed

    Muqbil, Irfana; Wu, Jack; Aboukameel, Amro; Mohammad, Ramzi M; Azmi, Asfar S

    2014-08-01

    Epithelial-to-mesenchymal transition (EMT) and the reverse process (MET) play central role in organ developmental biology. It is a fine tuned process that when disturbed leads to pathological conditions especially cancers with aggressive and metastatic behavior. Snail is an oncogene that has been well established to be a promoter of EMT through direct repression of epithelial morphology promoter E-cadherin. It can function in the nucleus, in the cytosol and as discovered recently, extracellularly through secretory vesicular structures. The intracellular transport of snail has for long been shown to be regulated by the nuclear pore complex. One of the Karyopherins, importin alpha, mediates snail import, while exportin 1 (Xpo1) also known as chromosome maintenance region 1 (CRM1) is its major nuclear exporter. A number of additional biological regulators are emerging that directly modulate Snail stability by altering its subcellular localization. These observations indicate that targeting the nuclear transport machinery could be an important and as of yet, unexplored avenue for therapeutic intervention against the EMT processes in cancer. In parallel, a number of novel agents that disrupt nuclear transport have recently been discovered and are being explored for their anti-cancer effects in the early clinical settings. Through this review we provide insights on the mechanisms regulating snail subcellular localization and how this impacts EMT. We discuss strategies on how the nuclear transport function can be harnessed to rein in EMT through modulation of snail signaling. PMID:24954011

  8. Snail Nuclear Transport: the Gateways Regulating Epithelial-to-Mesenchymal Transition?

    PubMed Central

    Muqbil, Irfana; Wu, Jack; Aboukameel, Amro; Mohammad, Ramzi M.; Azmi, Asfar S.

    2014-01-01

    Epithelial-to-mesenchymal transition (EMT) and the reverse process (MET) plays central role in organ developmental biology. It is a fine tuned process that when disturbed leads to pathological conditions especially cancers with aggressive and metastatic behavior. Snail is an oncogene that has been well established to be a promoter of EMT through direct repression of epithelial morphology promoter E-cadherin. It can function in the nucleus, in the cytosol and as discovered recently, extracellularly through secretory vesicular structures. The intracellular transport of snail has for long been shown to be regulated by the nuclear pore complex. One of the Karyopherins, importin alpha, mediates snail import, while importin beta/exportin 1 (Xpo1) or chromosome maintenance region 1 (CRM1) is its major nuclear exporter. A number of additional biological regulators are emerging that directly modulate Snail stability by altering its subcellular localization. These observations indicate that targeting the nuclear transport machinery could be an important and as of yet, unexplored avenue for therapeutic intervention against the EMT processes in cancer. In parallel, a number of novel agents that disrupt nuclear transport have recently been discovered and are being explored for their anti-cancer effects in the early clinical settings. Through this review we provide insights on the mechanisms regulating snail subcellular localization and how this impacts EMT. We discuss strategies on how the nuclear transport function can be harnessed to rein in EMT through modulation of snail signaling. PMID:24954011

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 48 CFR 247.372 - DD Form 1654, Evaluation of Transportation Cost Factors.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false DD Form 1654, Evaluation... Transportation in Supply Contracts 247.372 DD Form 1654, Evaluation of Transportation Cost Factors. Contracting personnel may use the DD Form 1654 to furnish information to the transportation office for development...

  15. 48 CFR 247.372 - DD Form 1654, Evaluation of Transportation Cost Factors.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false DD Form 1654, Evaluation... Transportation in Supply Contracts 247.372 DD Form 1654, Evaluation of Transportation Cost Factors. Contracting personnel may use the DD Form 1654 to furnish information to the transportation office for development...

  16. 48 CFR 247.372 - DD Form 1654, Evaluation of Transportation Cost Factors.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false DD Form 1654, Evaluation... Transportation in Supply Contracts 247.372 DD Form 1654, Evaluation of Transportation Cost Factors. Contracting personnel may use the DD Form 1654 to furnish information to the transportation office for development...

  17. 48 CFR 247.372 - DD Form 1654, Evaluation of Transportation Cost Factors.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false DD Form 1654, Evaluation... Transportation in Supply Contracts 247.372 DD Form 1654, Evaluation of Transportation Cost Factors. Contracting personnel may use the DD Form 1654 to furnish information to the transportation office for development...

  18. 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

    NA

    2001-02-15

    The Yucca Mountain Draft Environmental Impact Statement (DEIS) analysis addressed the potential for transporting spent nuclear fuel and high-level radioactive waste from 77 origins for 34 types of spent fuel and high-level radioactive waste, 49,914 legal weight truck shipments, and 10,911 rail shipments. The analysis evaluated transportation over 59,250 unique shipment links for travel outside Nevada (shipment segments in urban, suburban or rural zones by state), and 22,611 links in Nevada. In addition, the analysis modeled the behavior of 41 isotopes, 1091 source terms, and used 8850 food transfer factors (distinct factors by isotope for each state). The analysis also used mode-specific accident rates for legal weight truck, rail, and heavy haul truck by state, and barge by waterway. This complex mix of data and information required an innovative approach to assess the transportation impacts. The approach employed a Microsoft{reg_sign} Access database tool that incorporated data from many sources, including unit risk factors calculated using the RADTRAN IV transportation risk assessment computer program. Using Microsoft{reg_sign} Access, the analysts organized data (such as state-specific accident and fatality rates) into tables and developed queries to obtain the overall transportation impacts. Queries are instructions to the database describing how to use data contained in the database tables. While a query might be applied to thousands of table entries, there is only one sequence of queries that is used to calculate a particular transportation impact. For example, the incident-free dose to off-link populations in a state is calculated by a query that uses route segment lengths for each route in a state that could be used by shipments, populations for each segment, number of shipments on each segment, and an incident-free unit risk factor calculated using RADTRAN IV. In addition to providing a method for using large volumes of data in the calculations, the

  19. 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.

  20. Increased glucose transport in response to phorbol ester growth factors, and insulin: relationship to phosphorylation of the glucose transporter

    SciTech Connect

    Allard, W.J.; Gibbs, E.M.; Witters, L.A.; Lienhard, G.E.

    1986-05-01

    The authors have examined the relationship between the increase in glucose transport induced by phorbol myristate acetate (PMA), EGF, PDGF, and insulin and the phosphorylation state of the glucose transporter in human fibroblasts. To assay transport, cells were cultured in medium with 10% serum for 5 days and then for 2 days in phosphate-free medium with 5% serum. Exposure to each agonist stimulated transport, as measured by the uptake of /sup 3/H-2-deoxyglucose over a 2 min period. Values for maximal percent stimulation, time needed to reach maximal stimulation, and concentration required to achieve half-maximal stimulation were as follows: PMA, 80%, 30 min, 2 nM; EGF, 30%, 10 min, 0.2 nM; Insulin, 45%, 10 min, 17 nM. In the case of PDGF, uptake was stimulated 65% by treatment with 0.7 or 1.4 nM for 20 min. Phosphorylation of the glucose transporter was measured in cells cultured for 5-7 days in medium with 10% serum and exposed to 670 ..mu..Ci/ml /sup 32/P/sub i/ for 100 min. The agonist was then added at a saturating dose for 20 min, and the glucose transporter was immunoprecipitated from cell lysates using a monoclonal antibody. Under these conditions, no basal phosphorylation of the transporter was detected, and only phorbol ester stimulated significant incorporation of phosphate into the transport protein. Experiments are currently in progress to quantitate transporter phosphorylation under conditions identical to those used for the assay of transport. These results suggest that while the transporter is a substrate for protein kinase C in vivo, phosphorylation of the transporter is not required for increased transport in response to growth factors and insulin.

  1. A quantitative analysis of nuclear factor I/DNA interactions.

    PubMed Central

    Meisterernst, M; Gander, I; Rogge, L; Winnacker, E L

    1988-01-01

    Nuclear factor I (NFI) was purified to homogeneity from porcine liver by DNA-affinity chromatography and displays a single band with a molecular weight of 36 kDa in SDS-polyacrylamide gels. The purified protein was used to determine absolute equilibrium binding constants by gel retardation techniques for a variety of DNA fragments with genuine or mutated NFI binding sites and a number of DNA fragments derived from various eukaryotic promoters carrying the CCAAT-box as a half-site for NFI binding. We present a model which allows prediction of the functional significance of mutated NFI binding-sites from sequence data. The data suggest that the single molecular species of NFI from porcine liver may not be able to recognize and activate the -CCAAT- promoter element in vivo without additional interactions, e.g. with other proteins. Images PMID:3380685

  2. Nuclear factor kappa B role in inflammation associated gastrointestinal malignancies

    PubMed Central

    Gambhir, Sahil; Vyas, Dinesh; Hollis, Michael; Aekka, Apporva; Vyas, Arpita

    2015-01-01

    Nuclear factor kappa B (NF-κB) has an established role in the regulation of innate immunity and inflammation. NF-κB is also involved in critical mechanisms connecting inflammation and cancer development. Recent investigations suggest that the NF-κB signaling cascade may be the central mediator of gastrointestinal malignancies including esophageal, gastric and colorectal cancers. This review will explore NF-κB’s function in inflammation-associated gastrointestinal malignancies, highlighting its oncogenic contribution to each step of carcinogenesis. NF-κB’s role in the inflammation-to-carcinoma sequence in gastrointestinal malignancies warrants stronger emphasis upon targeting this pathway in achieving greater therapeutic efficacy. PMID:25805923

  3. Transport of nuclear-encoded proteins into secondarily evolved plastids.

    PubMed

    Hempel, Franziska; Bozarth, Andrew; Sommer, Maik S; Zauner, Stefan; Przyborski, Jude M; Maier, Uwe-G

    2007-09-01

    Many algal groups evolved by engulfment and intracellular reduction of a eukaryotic phototroph within a heterotrophic cell. Via this process, so-called secondary plastids evolved, surrounded by three or four membranes. In these organisms most of the genetic material encoding plastid functions is localized in the cell nucleus, with the result that many proteins have to pass three, four, or even five membranes to reach their final destination within the plastid. In this article, we review recent models and findings that help to explain important cellular mechanisms involved in the complex process of protein transport into secondary plastids. PMID:17696773

  4. 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.

  5. 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.

  6. 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.

  7. Specific interaction with the nuclear transporter importin α2 can modulate paraspeckle protein 1 delivery to nuclear paraspeckles

    PubMed Central

    Major, Andrew T.; Hogarth, Cathryn A.; Miyamoto, Yoichi; Sarraj, Mai A.; Smith, Catherine L.; Koopman, Peter; Kurihara, Yasuyuki; Jans, David A.; Loveland, Kate L.

    2015-01-01

    Importin (IMP) superfamily members mediate regulated nucleocytoplasmic transport, which is central to key cellular processes. Although individual IMPα proteins exhibit dynamic synthesis and subcellular localization during cellular differentiation, including during spermatogenesis, little is known of how this affects cell fate. To investigate how IMPαs control cellular development, we conducted a yeast two-hybrid screen for IMPα2 cargoes in embryonic day 12.5 mouse testis, a site of peak IMPα2 expression coincident with germ-line masculization. We identified paraspeckle protein 1 (PSPC1), the original defining component of nuclear paraspeckles, as an IMPα2-binding partner. PSPC1-IMPα2 binding in testis was confirmed in immunoprecipitations and pull downs, and an enzyme-linked immunosorbent assay–based assay demonstrated direct, high-affinity PSPC1 binding to either IMPα2/IMPβ1 or IMPα6/IMPβ1. Coexpression of full-length PSPC1 and IMPα2 in HeLa cells yielded increased PSPC1 localization in nuclear paraspeckles. High-throughput image analysis of >3500 cells indicated IMPα2 levels can directly determine PSPC1-positive nuclear speckle numbers and size; a transport-deficient IMPα2 isoform or small interfering RNA knockdown of IMPα2 each reduced endogenous PSPC1 accumulation in speckles. This first validation of an IMPα2 nuclear import cargo in fetal testis provides novel evidence that PSPC1 delivery to paraspeckles, and consequently paraspeckle function, may be controlled by modulated synthesis of specific IMPs. PMID:25694451

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

    Energy Science and Technology Software Center (ESTSC)

    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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

    ...This notice announces an open meeting of the Transportation and Storage (T&S) Subcommittee. The T&S Subcommittee is a subcommittee of the Blue Ribbon Commission on America's Nuclear Future (the Commission). The establishment of subcommittees is authorized in the Commission's charter. The Commission was organized pursuant to the Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) (the......

  14. 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

    ...This notice announces an open meeting of the Transportation and Storage (T&S) Subcommittee. The T&S Subcommittee is a subcommittee of the Blue Ribbon Commission on America's Nuclear Future (the Commission). The establishment of subcommittees is authorized in the Commission's charter. The Commission was organized pursuant to the Federal Advisory Committee Act (Pub. L. 92-463, 86 Stat. 770) (the......

  15. Cofactor Requirements for Nuclear Export of Rev Response Element (Rre)–And Constitutive Transport Element (Cte)–Containing Retroviral Rnas

    PubMed Central

    Hofmann, Wilma; Reichart, Beate; Ewald, Andrea; Müller, Eleonora; Schmitt, Iris; Stauber, Roland H.; Lottspeich, Friedrich; Jockusch, Brigitte M.; Scheer, Ulrich; Hauber, Joachim; Dabauvalle, Marie-Christine

    2001-01-01

    Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the export receptor CRM1/exportin1. However, additional protein factors interacting with leucine-rich NESs have been described. Here, we investigate human immunodeficiency virus type 1 (HIV-1) Rev-mediated nuclear export and Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE)–mediated nuclear export in microinjected Xenopus laevis oocytes. We show that eukaryotic initiation factor 5A (eIF-5A) is essential for Rev and Rev-mediated viral RNA export, but not for nuclear export of CTE RNA. In vitro binding studies demonstrate that eIF-5A is required for efficient interaction of Rev–NES with CRM1/exportin1 and that eIF-5A interacts with the nucleoporins CAN/nup214, nup153, nup98, and nup62. Quite unexpectedly, nuclear actin was also identified as an eIF-5A binding protein. We show that actin is associated with the nucleoplasmic filaments of nuclear pore complexes and is critically involved in export processes. Finally, actin- and energy-dependent nuclear export of HIV-1 Rev is reconstituted by using a novel in vitro egg extract system. In summary, our data provide evidence that actin plays an important functional role in nuclear export not only of retroviral RNAs but also of host proteins such as protein kinase inhibitor (PKI). PMID:11238447

  16. 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

  17. Hepatocyte nuclear factor-4α, a multifunctional nuclear receptor associated with cardiovascular disease and cholesterol catabolism.

    PubMed

    Tavares-Sanchez, Olga Lidia; Rodriguez, Carmen; Gortares-Moroyoqui, Pablo; Estrada, Maria Isabel

    2015-01-01

    Cardiovascular diseases (CVDs), the leading cause of death worldwide, are associated with high plasma cholesterol levels. The conversion of cholesterol to bile acids (BAs) accounts for about 50% of total cholesterol elimination from the body. This phenomenon occurs in the liver and is regulated by nuclear receptors such as hepatocyte nuclear factor-4α (HNF-4α). Therefore, special emphasis is given to HNF-4α properties and its multifunctional role, particularly in the conversion of cholesterol to BAs. HNF-4α is a highly conserved transcription factor that has the potential capacity to transactivate a vast number of genes, including CYP7 which codes for cholesterol 7α-hydroxylase (CYP7A1; EC 1.14.13.17), the rate-limiting enzyme of BA biosynthesis. The fact that HNF-4α transactivation potential can be modulated via phosporylation is of particular interest. Additional findings on structural and functional characteristics of HNF-4α may eventually present alternatives to control the levels of cholesterol in the body and consequently reduce the risk of CVDs. PMID:24848804

  18. Analytical Solutions for Sequentially Reactive Transport with Different Retardation Factors

    SciTech Connect

    Sun, Y; Buscheck, T A; Mansoor, K; Lu, X

    2001-08-01

    Integral transforms have been widely used for deriving analytical solutions for solute transport systems. Often, analytical solutions can only be written in closed form in frequency domains and numerical inverse-transforms have to be involved to obtain semi-analytical solutions in the time domain. For this reason, previously published closed form solutions are restricted either to a small number of species or to the same retardation assumption. In this paper, we applied the solution scheme proposed by Bauer et al. in the time domain. Using available analytical solutions of a single species transport with first-order decay without coupling with its parent species concentration as fundamental solutions, a daughter species concentration can be expressed as a linear function of those fundamental solutions. The implementation of the solution scheme is straight forward and exact analytical solutions are derived for one- and three-dimensional transport systems.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Anomalous solute transport in saturated porous media: Relating transport model parameters to electrical and nuclear magnetic resonance properties

    NASA Astrophysics Data System (ADS)

    Swanson, Ryan D.; Binley, Andrew; Keating, Kristina; France, Samantha; Osterman, Gordon; Day-Lewis, Frederick D.; Singha, Kamini

    2015-02-01

    The advection-dispersion equation (ADE) fails to describe commonly observed non-Fickian solute transport in saturated porous media, necessitating the use of other models such as the dual-domain mass-transfer (DDMT) model. DDMT model parameters are commonly calibrated via curve fitting, providing little insight into the relation between effective parameters and physical properties of the medium. There is a clear need for material characterization techniques that can provide insight into the geometry and connectedness of pore spaces related to transport model parameters. Here, we consider proton nuclear magnetic resonance (NMR), direct-current (DC) resistivity, and complex conductivity (CC) measurements for this purpose, and assess these methods using glass beads as a control and two different samples of the zeolite clinoptilolite, a material that demonstrates non-Fickian transport due to intragranular porosity. We estimate DDMT parameters via calibration of a transport model to column-scale solute tracer tests, and compare NMR, DC resistivity, CC results, which reveal that grain size alone does not control transport properties and measured geophysical parameters; rather, volume and arrangement of the pore space play important roles. NMR cannot provide estimates of more-mobile and less-mobile pore volumes in the absence of tracer tests because these estimates depend critically on the selection of a material-dependent and flow-dependent cutoff time. Increased electrical connectedness from DC resistivity measurements are associated with greater mobile pore space determined from transport model calibration. CC was hypothesized to be related to length scales of mass transfer, but the CC response is unrelated to DDMT.

  4. Nuclear Factor-Erythroid-2-Related Factor 2 in Aging and Lung Fibrosis.

    PubMed

    Swamy, Shobha M; Rajasekaran, Namakkal S; Thannickal, Victor J

    2016-07-01

    Aging and age-related diseases have been associated with elevated oxidative stress, which may be related to increased production of reactive species and/or a deficiency in antioxidant defenses. The nuclear factor-erythroid-2-related factor 2 (Nrf2)-mediated antioxidant response pathway maintains cellular reduction-oxidation homeostasis by inducing the transcription of an array of cytoprotective genes. However, there is evidence of impaired Nrf2 response in aging contributing to age-related fibrotic diseases. Herein, we review mechanisms for the dysregulation of Nrf2 signaling in aging. This understanding will pave the way for the design of novel therapeutic strategies that restore Nrf2 signaling to reestablish cellular homeostasis in aging and age-related fibrotic diseases. PMID:27338106

  5. 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).

  6. 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...

  7. 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

  8. Nuclear Factor-kappa B Signaling in Skeletal Muscle Atrophy

    PubMed Central

    Li, Hong; Malhotra, Shweta; Kumar, Ashok

    2008-01-01

    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-κB) is one of most important signaling pathways linked to the loss of skeletal muscle mass in various physiological and pathophysiological conditions. Activation of NF-κB 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-κB 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-κB in skeletal muscle with particular reference to different models of muscle-wasting and the development of novel therapy. PMID:18574572

  9. 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.

  10. 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.

  11. Nuclear-cytoplasmic transport of EGFR involves receptor endocytosis, importin beta1 and CRM1.

    PubMed

    Lo, Hui-Wen; Ali-Seyed, Mohamed; Wu, Yadi; Bartholomeusz, Geoffrey; Hsu, Sheng-Chieh; Hung, Mien-Chie

    2006-08-15

    Many receptor tyrosine kinases (RTKs) can be detected in the cell nucleus, such as EGFR, HER-2, HER-3, HER-4, and fibroblast growth factor receptor. EGFR, HER-2 and HER-4 contain transactivational activity and function as transcription co-factors to activate gene promoters. High EGFR in tumor nuclei correlates with increased tumor proliferation and poor survival in cancer patients. However, the mechanism by which cell-surface EGFR translocates into the cell nucleus remains largely unknown. Here, we found that EGFR co-localizes and interacts with importins alpha1/beta1, carriers that are critical for macromolecules nuclear import. EGFR variant mutated at the nuclear localization signal (NLS) is defective in associating with importins and in entering the nuclei indicating that EGFR's NLS is critical for EGFR/importins interaction and EGFR nuclear import. Moreover, disruption of receptor internalization process using chemicals and forced expression of dominant-negative Dynamin II mutant suppressed nuclear entry of EGFR. Additional evidences suggest an involvement of endosomal sorting machinery in EGFR nuclear translocalization. Finally, we found that nuclear export of EGFR may involve CRM1 exportin as we detected EGFR/CRM1 interaction and markedly increased nuclear EGFR following exposure to leptomycin B, a CRM1 inhibitor. Collectively, these data suggest the importance of receptor endocytosis, endosomal sorting machinery, interaction with importins alpha1/beta1, and exportin CRM1 in EGFR nuclear-cytoplasmic trafficking. Together, our work sheds light into the nature and regulation of the nuclear EGFR pathway and provides a plausible mechanism by which cells shuttle cell-surface EGFR and potentially other RTKs through the nuclear pore complex and into the nuclear compartment. PMID:16552725

  12. 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.

  13. Operational design factors for advanced space transportation vehicles

    NASA Astrophysics Data System (ADS)

    Whitehair, C. L.; Hickman, R. A.; Adams, J. D.; Wolfe, M. G.

    1992-08-01

    The tools and techniques needed to provide design decision-makers with balanced quantitative assessments of the potential operability consequences of their decisions are addressed. The factors controlling operability are identified, and a methodology to predict the impact of these factors on a specific launch vehicle is developed. Requirements to control these factors are established, and analytical tools developed specifically for performing detailed simulations to verify specific operability characteristics are described. An approach to collect, store, organize, and access high-quality historical, current, and future launch system data for the benefit of the USAF and the U.S. launch system community at large is outlined.

  14. 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

  15. Atmospheric radionuclides transported to Fukuoka, Japan remote from the Fukushima Dai-ichi nuclear power complex following the nuclear accident.

    PubMed

    Momoshima, N; Sugihara, S; Ichikawa, R; Yokoyama, H

    2012-09-01

    Radionuclides were detected from the Fukushima nuclear accident at Fukuoka, Japan, 1000 km west of the Fukushima Dai-ichi nuclear power complex. Iodine-131 was first detected 3 d after the accident, indicating that it was probably transported dispersively because of local meteorological conditions, and not global air circulation. The maximum concentrations, 5.07 mBq m(-3) for (131)I, 4.04 mBq m(-3) for (134)Cs, and 4.12 mBq m(-3) for (137)Cs, were recorded in particles collected on April 6, 2011. However, these concentration levels decreased below the detection limit by April 26, 2011. Gaseous (131)I accounted for 30%-67% of the total (131)I content. The increase in dose by inhalation was negligible at Fukuoka. PMID:21962481

  16. 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.

  17. 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.

  18. Modification of generalized vector form factors and transverse charge densities of the nucleon in nuclear matter

    NASA Astrophysics Data System (ADS)

    Jung, Ju-Hyun; Yakhshiev, Ulugbek; Kim, Hyun-Chul

    2016-03-01

    We investigate the medium modification of the generalized vector form factors of the nucleon, which include the electromagnetic and energy-momentum tensor form factors, based on an in-medium modified π -ρ -ω soliton model. We find that the vector form factors of the nucleon in nuclear matter fall off faster than those in free space, which implies that the charge radii of the nucleon become larger in nuclear medium than in free space. We also compute the corresponding transverse charge densities of the nucleon in nuclear matter, which clearly reveal the increasing of the nucleon size in nuclear medium.

  19. 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.

  20. 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

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

    PubMed

    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 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. PMID:21179205

  2. {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.

  3. Major factors impacting costs of nuclear power plants

    SciTech Connect

    Tan, Z.A.; James, D.W.

    1985-11-01

    China is striving to complete construction of 10,000 MWe of nuclear power plants by the year 2000. The Chinese government is concerned about the costs and is interested in minimizing the economic risks. The paper discusses the problems of cost control in the US and the special problems expected as China begins its nuclear power development.

  4. 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.

  5. 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.

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

    PubMed

    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. PMID:27058170

  7. Microbial effects on the radionuclide transport in a deep nuclear waste repository

    SciTech Connect

    Spor, H.; Trescinski, M.; Libert, M.F.

    1993-12-31

    This study deals with the effects of microorganisms on the transport of radionuclides under deep nuclear-waste disposal conditions. Metabolism of a cellulolytic microorganism is studied. Cellulose, as a carbon source, is representative of nuclear waste. A pilot device allows the study of the general effect of microrganisms. Bioleaching of radionuclides by a fungal culture is performed on columns of clay and cement used as engineered barriers. Cesium and Uranium had been incorporated into matrices prior to the tests. Operating conditions have been choosen according to realistic conditions of a deep repository. The production of organic acids by microorganisms is qualitatively and quantitatively determined. In addition, direct effects of microorganisms (biosorption, bioaccumulation) and indirect effects (complexing agents issued from the diodegradation of cellulose) on the transport and/or retardation of radionuclides are studied.

  8. 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.

  9. 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

  10. 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

  11. Factors Influencing Observed Tillage Impacts on Herbicide Transport

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 factors such as ...

  12. 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.

  13. 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

  14. 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.

  15. Environmental Baseline File National Transportation

    SciTech Connect

    Harris, M.

    1999-06-01

    This Environmental Baseline File summarizes and consolidates information related to the national-level transportation of commercial spent nuclear fuel. Topics addressed include: shipments 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.

  16. Adverse events during intrahospital transport of critically ill patients: incidence and risk factors

    PubMed Central

    2013-01-01

    Background Transport of critically ill patients for diagnostic or therapeutic procedures is at risk of complications. Adverse events during transport are common and may have significant consequences for the patient. The objective of the study was to collect prospectively adverse events that occurred during intrahospital transports of critically ill patients and to determine their risk factors. Methods This prospective, observational study of intrahospital transport of consecutively admitted patients with mechanical ventilation was conducted in a 38-bed intensive care unit in a university hospital from May 2009 to March 2010. Results Of 262 transports observed (184 patients), 120 (45.8%) were associated with adverse events. Risk factors were ventilation with positive end-expiratory pressure >6 cmH2O, sedation before transport, and fluid loading for intrahospital transports. Within these intrahospital transports with adverse events, 68 (26% of all intrahospital transports) were associated with an adverse event affecting the patient. Identified risk factors were: positive end-expiratory pressure >6 cmH2O, and treatment modification before transport. In 44 cases (16.8% of all intrahospital transports), adverse event was considered serious for the patient. In our study, adverse events did not statistically increase ventilator-associated pneumonia, time spent on mechanical ventilation, or length of stay in the intensive care unit. Conclusions This study confirms that the intrahospital transports of critically ill patients leads to a significant number of adverse events. Although in our study adverse events have not had major consequences on the patient stay, efforts should be made to decrease their incidence. PMID:23587445

  17. 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.

  18. 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

  19. 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

  20. 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. PMID:12611653

  1. 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

  2. Variability in hepatic expression of organic anion transporter 7/SLC22A9, a novel pravastatin uptake transporter: impact of genetic and regulatory factors.

    PubMed

    Emami Riedmaier, A; Burk, O; van Eijck, B A C; Schaeffeler, E; Klein, K; Fehr, S; Biskup, S; Müller, S; Winter, S; Zanger, U M; Schwab, M; Nies, A T

    2016-08-01

    Human organic anion transporter 7 (OAT7, SLC22A9) is a hepatic transport protein poorly characterized so far. We therefore sought to identify novel OAT7 substrates and factors contributing to variable hepatic OAT7 expression. Using OAT7-expressing cells, pravastatin was identified as a substrate. Hepatic SLC22A9/OAT7 mRNA and protein expression varied 28-fold and 15-fold, respectively, in 126 Caucasian liver samples. Twenty-four variants in SLC22A9 were genotyped, including three rare missense variants (rs377211288, rs61742518, rs146027075), which occurred only heterozygously. No variant significantly affected hepatic SLC22A9/OAT7 expression. The three missense variants, however, showed functional consequences when expressed in vitro. Hepatic nuclear factor 4-alpha (HNF4α) emerged as a major transcriptional regulator of SLC22A9 by a series of in silico and in vitro analyses. In conclusion, pravastatin is the first identified OAT7 drug substrate. Substantial inter-individual variability in hepatic OAT7 expression, majorly driven by HNF4α, may contribute to pravastatin drug disposition and might affect response.The Pharmacogenomics Journal advance online publication, 4 August 2015; doi:10.1038/tpj.2015.55. PMID:26239079

  3. Perceived Environmental and Personal Factors Associated with Walking and Cycling for Transportation in Taiwanese Adults

    PubMed Central

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

    2015-01-01

    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. PMID:25689349

  4. 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.

  5. 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.

  6. Advances in nuclear data and all-particle transport for radiation oncology

    SciTech Connect

    White, R.M.; Chadwick, M.B.; Chandler, W.P.; Hartmann Siantar, C.L.; Westbrook, C.K.

    1994-05-01

    Fast neutrons have been used to treat over 15,000 cancer patients worldwide and proton therapy is rapidly emerging as a treatment of choice for tumors around critical anatomical structures. Neutron therapy requires evaluated data to {approximately}70 MeV while proton therapy requires data to {approximately}250 MeV. Collaboration between Lawrence Livermore National Laboratory (LLNL) and the medical physics community has revealed limitations in nuclear cross section evaluations and radiation transport capabilities that have prevented neutron and proton radiation therapy centers from using Monte Carlo calculations to accurately predict dose in patients. These evaluations require energy- and angle-dependent cross sections for secondary neutrons, charged-particles and recoil nuclei. We are expanding the LLNL nuclear databases to higher energies for biologically important elements and have developed a three-dimensional, all-particle Monte Carlo radiation transport code that uses computer-assisted-tomography (CT) images as the input mesh. This code, called PEREGRINE calculates dose distributions in the human body and can be used as a tool to determine the dependence of dose on details of the evaluated nuclear data. In this paper, we will review the status of the nuclear data required for neutron and proton therapy, describe the capabilities of the PEREGRINE package, and show the effects of tissue inhomogeneities on dose distribution.

  7. 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

  8. Costs and impacts of transporting nuclear waste to candidate repository sites

    SciTech Connect

    McSweeney, T.I.; Peterson, R.W.; Gupta, R.

    1983-12-31

    In this paper, a status report on the current estimated costs and impacts of transporting high-level nuclear wastes to candidate disposal sites is given. Impacts in this analysis are measured in terms of risk to public health and safety. Since it is difficult to project the status of the nuclear industry to the time of repository operation - 20 to 50 years in the future - particular emphasis in the paper is placed on the evaluation of uncertainties. The first part of this paper briefly describes the characteristics of the waste that must be transported to a high-level waste disposal site. This discussion is followed by a section describing the characteristics of the waste transport system. Subsequent sections describe the costs and risk assessments of waste transport. Finally, in a concluding section, the effect of the uncertainties in the definition of the waste disposal system on cost and risk levels is evaluated. This last section also provides some perspectives on the magnitude of the cost and risk levels relative to other comparable costs and risks generally encountered. 13 references, 2 figures, 16 tables.

  9. 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.

  10. 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